diff --git a/configs/config_pseudomonas_33245.tsv b/configs/config_pseudomonas_33245.tsv index f95d5658..204d0254 100644 --- a/configs/config_pseudomonas_33245.tsv +++ b/configs/config_pseudomonas_33245.tsv @@ -8,6 +8,9 @@ normalized_compendium_filename "/home/alexandra/Documents/Data/Generic_expressio shared_genes_filename "/home/alexandra/Documents/Data/Generic_expression_patterns/shared_genes_pseudomonas.pickle" scaler_filename "/home/alexandra/Documents/Data/Generic_expression_patterns/scaler_transform_pseudomonas.pickle" rank_genes_by "logFC" +reference_gene_filename "GAPE_proportions.txt" +reference_gene_name_col "gene id" +reference_rank_col "prop DEGs" pathway_DB_filename "https://raw.githubusercontent.com/greenelab/adage/master/Node_interpretation/pseudomonas_KEGG_terms.txt" gsea_statistic 'log2FoldChange' rank_pathways_by "padj" diff --git a/configs/config_pseudomonas_pao1.tsv b/configs/config_pseudomonas_pao1.tsv new file mode 100644 index 00000000..fe4fbe6c --- /dev/null +++ b/configs/config_pseudomonas_pao1.tsv @@ -0,0 +1,28 @@ +local_dir "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/" +dataset_name "pseudomonas_analysis" +raw_template_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/raw_pseudomonas_template_data.tsv" +processed_template_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/processed_pseudomonas_template_data.tsv" +raw_compendium_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/raw_pseudomonas_compendium_data.tsv" +processed_compendium_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/processed_pseudomonas_compendium_data.tsv" +normalized_compendium_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/normalized_pseudomonas_compendium_data.tsv" +shared_genes_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/shared_genes_pseudomonas.pickle" +scaler_filename "/home/alexandra/Documents/Data/Generic_expression_patterns_pao1/scaler_transform_pseudomonas.pickle" +rank_genes_by "logFC" +reference_gene_filename "GAPE_proportions.txt" +reference_gene_name_col "gene id" +reference_rank_col "prop DEGs" +pathway_DB_filename "https://raw.githubusercontent.com/greenelab/adage/master/Node_interpretation/pseudomonas_KEGG_terms.txt" +gsea_statistic 'log2FoldChange' +rank_pathways_by "padj" +NN_architecture "NN_2500_30_pao1" +learning_rate 0.001 +batch_size 10 +epochs 100 +kappa 0.01 +intermediate_dim 2500 +latent_dim 30 +epsilon_std 1.0 +validation_frac 0.25 +project_id "E-GEOD-33245" +metadata_colname 'ml_data_source' +num_simulated 25 \ No newline at end of file diff --git a/generic_expression_patterns_modules/process.py b/generic_expression_patterns_modules/process.py index 9768676b..0ed5e02f 100644 --- a/generic_expression_patterns_modules/process.py +++ b/generic_expression_patterns_modules/process.py @@ -358,15 +358,12 @@ def map_recount2_data( ofh.write(sample_id + "\t" + "\t".join(output_values) + "\n") -# TO DO: decide if not needed def process_raw_template_pseudomonas( processed_compendium_filename, project_id, dataset_name, metadata_colname, - sample_id_metadata_filename, raw_template_filename, - processed_template_filename, ): """ Create processed pseudomonas template data file based on @@ -388,23 +385,6 @@ def process_raw_template_pseudomonas( template_data.to_csv(raw_template_filename, sep="\t") - sample_ids_to_drop = set() - if os.path.exists(sample_id_metadata_filename): - # Read in metadata and get samples to be dropped: - metadata = pd.read_csv( - sample_id_metadata_filename, sep="\t", header=0, index_col=0 - ) - sample_ids_to_drop = set(metadata[metadata["processing"] == "drop"].index) - - # Write the processed pseudomonas template output file on disk - with open(raw_template_filename) as ifh, open( - processed_template_filename, "w" - ) as ofh: - for idx, line in enumerate(ifh): - sample_id = line.split("\t")[0] - if idx == 0 or sample_id not in sample_ids_to_drop: - ofh.write(line) - def normalize_compendium( mapped_filename, normalized_filename, scaler_filename, @@ -444,17 +424,21 @@ def process_raw_compendium_pseudomonas( """ Create processed pseudomonas compendium data file based on raw compendium data file (`raw_filename`), and normalize the processed compendium. + + Note: This function was designed to processed data from the pseudomonas + compendium defined in the ADAGE paper + (https://msystems.asm.org/content/1/1/e00025-15). """ # Create processed pseudomonas compendium data file raw_compendium = pd.read_csv(raw_filename, header=0, index_col=0, sep="\t") - if raw_compendium.shape != (950, 5549): + if raw_compendium.shape[1] != 5549: processed_compendium = raw_compendium.T else: processed_compendium = raw_compendium - assert processed_compendium.shape == (950, 5549) + assert processed_compendium.shape[1] == 5549 # Save transformed compendium data processed_compendium.to_csv(processed_filename, sep="\t") diff --git a/generic_expression_patterns_modules/ranking.py b/generic_expression_patterns_modules/ranking.py index 670169c1..c81d33c5 100644 --- a/generic_expression_patterns_modules/ranking.py +++ b/generic_expression_patterns_modules/ranking.py @@ -19,6 +19,7 @@ from scipy import stats import pandas as pd import seaborn as sns +import matplotlib.pyplot as plt from sklearn.preprocessing import MinMaxScaler @@ -422,7 +423,9 @@ def get_shared_rank_scaled( ] # Get correlation - r, p, ci_low, ci_high = spearman_ci(0.95, shared_rank_scaled_df, 1000, data_type) + r, p, ci_low, ci_high = spearman_ci( + 0.95, shared_rank_scaled_df, 1000, ref_rank_col, data_type + ) correlations = {"r": r, "p": p, "ci_low": ci_low, "ci_high": ci_high} @@ -467,9 +470,15 @@ def compare_gene_ranking( marginal_kws={"color": "white"}, ) - fig.set_axis_labels( - "SOPHIE", "DE prior (Crow et. al. 2019)", fontsize=14, fontname="Verdana" - ) + if ref_rank_col == "DE_Prior_Rank": + fig.set_axis_labels( + "SOPHIE", "DE prior (Crow et. al. 2019)", fontsize=14, fontname="Verdana" + ) + elif ref_rank_col == "prop DEGs": + fig.set_axis_labels( + "SOPHIE", "GAPE (Stanton lab, 2020)", fontsize=14, fontname="Verdana" + ) + plt.colorbar() fig.savefig( output_figure_filename, @@ -480,7 +489,7 @@ def compare_gene_ranking( dpi=300, ) - return correlations + return correlations, shared_gene_rank_scaled_df def compare_pathway_ranking(summary_df, reference_filename, output_figure_filename): @@ -585,7 +594,7 @@ def add_pseudomonas_gene_name_col(summary_gene_ranks, base_dir): return summary_gene_ranks -def spearman_ci(ci, gene_rank_df, num_permutations, data_type): +def spearman_ci(ci, gene_rank_df, num_permutations, ref_rank_col, data_type): """ Returns spearman correlation score and confidence interval @@ -597,11 +606,13 @@ def spearman_ci(ci, gene_rank_df, num_permutations, data_type): Dataframe containing the our rank and Crow et. al. rank num_permutations: int The number of permutations to estimate the confidence interval + ref_rank_col: str + Name of column header containing reference ranks of genes data_type: 'DE' or 'GSA' """ if data_type.lower() == "de": r, p = stats.spearmanr( - gene_rank_df["Rank (simulated)"], gene_rank_df["DE_Prior_Rank"] + gene_rank_df["Rank (simulated)"], gene_rank_df[ref_rank_col] ) elif data_type.lower() == "gsa": r, p = stats.spearmanr( @@ -615,7 +626,7 @@ def spearman_ci(ci, gene_rank_df, num_permutations, data_type): if data_type.lower() == "de": r_perm, p_perm = stats.spearmanr( - sample["Rank (simulated)"], sample["DE_Prior_Rank"] + sample["Rank (simulated)"], sample[ref_rank_col] ) elif data_type.lower() == "gsa": r_perm, p_perm = stats.spearmanr( diff --git a/human_cancer_analysis/2_identify_generic_genes_pathways.ipynb b/human_cancer_analysis/2_identify_generic_genes_pathways.ipynb index 23a5cf6a..d129c548 100644 --- a/human_cancer_analysis/2_identify_generic_genes_pathways.ipynb +++ b/human_cancer_analysis/2_identify_generic_genes_pathways.ipynb @@ -1151,7 +1151,7 @@ "\n", "figure_filename = f\"gene_ranking_{col_to_rank_genes}.svg\"\n", "\n", - "ranking.compare_gene_ranking(\n", + "corr, shared_ranking = ranking.compare_gene_ranking(\n", " summary_gene_ranks,\n", " DE_prior_filename,\n", " ref_gene_col,\n", diff --git a/human_cancer_analysis/nbconverted/2_identify_generic_genes_pathways.py b/human_cancer_analysis/nbconverted/2_identify_generic_genes_pathways.py index 1ebfe1f5..f0624d9e 100644 --- a/human_cancer_analysis/nbconverted/2_identify_generic_genes_pathways.py +++ b/human_cancer_analysis/nbconverted/2_identify_generic_genes_pathways.py @@ -517,7 +517,7 @@ def shift_template_experiment_with_metadatafile( figure_filename = f"gene_ranking_{col_to_rank_genes}.svg" -ranking.compare_gene_ranking( +corr, shared_ranking = ranking.compare_gene_ranking( summary_gene_ranks, DE_prior_filename, ref_gene_col, diff --git a/human_general_analysis/2_identify_generic_genes_pathways.ipynb b/human_general_analysis/2_identify_generic_genes_pathways.ipynb index e92e9f9f..70fcdaec 100644 --- a/human_general_analysis/2_identify_generic_genes_pathways.ipynb +++ b/human_general_analysis/2_identify_generic_genes_pathways.ipynb @@ -1046,7 +1046,7 @@ "\n", "figure_filename = f\"gene_ranking_{col_to_rank_genes}.svg\"\n", "\n", - "ranking.compare_gene_ranking(\n", + "corr, shared_ranking = ranking.compare_gene_ranking(\n", " summary_gene_ranks,\n", " DE_prior_filename,\n", " ref_gene_col,\n", diff --git a/human_general_analysis/nbconverted/2_identify_generic_genes_pathways.py b/human_general_analysis/nbconverted/2_identify_generic_genes_pathways.py index 9ff21a42..d8b7ad5e 100644 --- a/human_general_analysis/nbconverted/2_identify_generic_genes_pathways.py +++ b/human_general_analysis/nbconverted/2_identify_generic_genes_pathways.py @@ -310,7 +310,7 @@ figure_filename = f"gene_ranking_{col_to_rank_genes}.svg" -ranking.compare_gene_ranking( +corr, shared_ranking = ranking.compare_gene_ranking( summary_gene_ranks, DE_prior_filename, ref_gene_col, diff --git a/other_enrichment_methods/nbconverted/1_simulate_data.py b/other_enrichment_methods/nbconverted/1_simulate_data.py index 8f78cdc7..942675bf 100644 --- a/other_enrichment_methods/nbconverted/1_simulate_data.py +++ b/other_enrichment_methods/nbconverted/1_simulate_data.py @@ -1,16 +1,15 @@ - # coding: utf-8 # # Simulate gene expression data -# +# # This notebook simulates gene expression data that can then be plugged into different enrichment methods # In[1]: -get_ipython().run_line_magic('load_ext', 'autoreload') -get_ipython().run_line_magic('load_ext', 'rpy2.ipython') -get_ipython().run_line_magic('autoreload', '2') +get_ipython().run_line_magic("load_ext", "autoreload") +get_ipython().run_line_magic("load_ext", "rpy2.ipython") +get_ipython().run_line_magic("autoreload", "2") import os import sys @@ -19,6 +18,7 @@ import pickle from rpy2.robjects import pandas2ri + pandas2ri.activate() from ponyo import utils, simulate_expression_data @@ -45,36 +45,28 @@ # Load params local_dir = params["local_dir"] -dataset_name = params['dataset_name'] -NN_architecture = params['NN_architecture'] -num_runs = params['num_simulated'] -project_id = params['project_id'] -metadata_col_id = params['metadata_colname'] -mapped_template_filename = params['mapped_template_filename'] -processed_template_filename = params['processed_template_filename'] -normalized_compendium_filename = params['normalized_compendium_filename'] -scaler_filename = params['scaler_filename'] -col_to_rank_genes = params['rank_genes_by'] -col_to_rank_pathways = params['rank_pathways_by'] -statistic = params['gsea_statistic'] -count_threshold = params['count_threshold'] +dataset_name = params["dataset_name"] +NN_architecture = params["NN_architecture"] +num_runs = params["num_simulated"] +project_id = params["project_id"] +metadata_col_id = params["metadata_colname"] +mapped_template_filename = params["mapped_template_filename"] +processed_template_filename = params["processed_template_filename"] +normalized_compendium_filename = params["normalized_compendium_filename"] +scaler_filename = params["scaler_filename"] +col_to_rank_genes = params["rank_genes_by"] +col_to_rank_pathways = params["rank_pathways_by"] +statistic = params["gsea_statistic"] +count_threshold = params["count_threshold"] # Load metadata file with grouping assignments for samples sample_id_metadata_filename = os.path.join( - base_dir, - dataset_name, - "data", - "metadata", - f"{project_id}_process_samples.tsv" + base_dir, dataset_name, "data", "metadata", f"{project_id}_process_samples.tsv" ) # Load metadata file with grouping assignments for samples metadata_filename = os.path.join( - base_dir, - dataset_name, - "data", - "metadata", - f"{project_id}_groups.tsv" + base_dir, dataset_name, "data", "metadata", f"{project_id}_groups.tsv" ) # Load pickled file @@ -87,22 +79,18 @@ # Output files gene_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_gene_summary_{project_id}.tsv" + base_dir, dataset_name, f"generic_gene_summary_{project_id}.tsv" ) pathway_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_pathway_summary_{project_id}.tsv" + base_dir, dataset_name, f"generic_pathway_summary_{project_id}.tsv" ) # ### Simulate experiments using selected template experiment -# +# # Workflow: -# +# # 1. Get the gene expression data for the selected template experiment # 2. Encode this experiment into a latent space using the trained VAE model # 3. Linearly shift the encoded template experiment in the latent space @@ -113,11 +101,11 @@ # Simulate multiple experiments -# This step creates the following files in "/pseudo_experiment/" directory: +# This step creates the following files in "/pseudo_experiment/" directory: # - selected_simulated_data_SRP012656_.txt # - selected_simulated_encoded_data_SRP012656_.txt # - template_normalized_data_SRP012656_test.txt -# in which "" is an integer in the range of [0, num_runs-1] +# in which "" is an integer in the range of [0, num_runs-1] os.makedirs(os.path.join(local_dir, "pseudo_experiment"), exist_ok=True) for run_id in range(num_runs): simulate_expression_data.shift_template_experiment( @@ -129,12 +117,12 @@ scaler, local_dir, base_dir, - run_id + run_id, ) # ## Process template and simulated experiments -# +# # * Remove samples not required for comparison # * Make sure ordering of samples matches metadata for proper comparison # * Make sure values are cast as integers for using DESeq @@ -145,25 +133,23 @@ if not os.path.exists(sample_id_metadata_filename): sample_id_metadata_filename = None - + stats.process_samples_for_DESeq( - mapped_template_filename, - metadata_filename, - processed_template_filename, - count_threshold, - sample_id_metadata_filename, - ) + mapped_template_filename, + metadata_filename, + processed_template_filename, + count_threshold, + sample_id_metadata_filename, +) for i in range(num_runs): simulated_filename = os.path.join( - local_dir, - "pseudo_experiment", - f"selected_simulated_data_{project_id}_{i}.txt" + local_dir, "pseudo_experiment", f"selected_simulated_data_{project_id}_{i}.txt" ) out_simulated_filename = os.path.join( local_dir, "pseudo_experiment", - f"selected_simulated_data_{project_id}_{i}_processed.txt" + f"selected_simulated_data_{project_id}_{i}_processed.txt", ) stats.process_samples_for_DESeq( simulated_filename, @@ -171,5 +157,5 @@ out_simulated_filename, count_threshold, sample_id_metadata_filename, -) + ) diff --git a/other_enrichment_methods/nbconverted/3_viz_pathway_ranking.py b/other_enrichment_methods/nbconverted/3_viz_pathway_ranking.py index 4fee2d31..e1f7f2d1 100644 --- a/other_enrichment_methods/nbconverted/3_viz_pathway_ranking.py +++ b/other_enrichment_methods/nbconverted/3_viz_pathway_ranking.py @@ -1,18 +1,17 @@ - # coding: utf-8 # # Visualize pathway ranking -# +# # This notebook will visualize pathway ranking obtained by the different enrichment analysis methods. -# +# # **Note**: This notebook is expecting outputs for all enrichment methods generated by the [previous notebook](2_apply_enrichment_method.ipynb) # In[1]: -get_ipython().run_line_magic('load_ext', 'autoreload') -get_ipython().run_line_magic('load_ext', 'rpy2.ipython') -get_ipython().run_line_magic('autoreload', '2') +get_ipython().run_line_magic("load_ext", "autoreload") +get_ipython().run_line_magic("load_ext", "rpy2.ipython") +get_ipython().run_line_magic("autoreload", "2") import os import pandas as pd @@ -54,7 +53,7 @@ "GSVA": "ES", "ROAST": "FDR", "CAMERA": "FDR", - "ORA": "p.adjust" + "ORA": "p.adjust", } @@ -65,29 +64,19 @@ # Pathway summary files gsea_pathway_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_pathway_summary_{project_id}.tsv" + base_dir, dataset_name, f"generic_pathway_summary_{project_id}.tsv" ) gsva_pathway_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_pathway_summary_{project_id}_GSVA.tsv" + base_dir, dataset_name, f"generic_pathway_summary_{project_id}_GSVA.tsv" ) roast_pathway_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_pathway_summary_{project_id}_ROAST.tsv" + base_dir, dataset_name, f"generic_pathway_summary_{project_id}_ROAST.tsv" ) camera_pathway_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_pathway_summary_{project_id}_CAMERA.tsv" + base_dir, dataset_name, f"generic_pathway_summary_{project_id}_CAMERA.tsv" ) ora_pathway_summary_filename = os.path.join( - base_dir, - dataset_name, - f"generic_pathway_summary_{project_id}_ORA.tsv" + base_dir, dataset_name, f"generic_pathway_summary_{project_id}_ORA.tsv" ) @@ -95,11 +84,21 @@ # Pathway summary data -gsea_pathway_summary = pd.read_csv(gsea_pathway_summary_filename, sep="\t", index_col=0, header=0) -gsva_pathway_summary = pd.read_csv(gsva_pathway_summary_filename, sep="\t", index_col=0, header=0) -roast_pathway_summary = pd.read_csv(roast_pathway_summary_filename, sep="\t", index_col=0, header=0) -camera_pathway_summary = pd.read_csv(camera_pathway_summary_filename, sep="\t", index_col=0, header=0) -ora_pathway_summary = pd.read_csv(ora_pathway_summary_filename, sep="\t", index_col=0, header=0) +gsea_pathway_summary = pd.read_csv( + gsea_pathway_summary_filename, sep="\t", index_col=0, header=0 +) +gsva_pathway_summary = pd.read_csv( + gsva_pathway_summary_filename, sep="\t", index_col=0, header=0 +) +roast_pathway_summary = pd.read_csv( + roast_pathway_summary_filename, sep="\t", index_col=0, header=0 +) +camera_pathway_summary = pd.read_csv( + camera_pathway_summary_filename, sep="\t", index_col=0, header=0 +) +ora_pathway_summary = pd.read_csv( + ora_pathway_summary_filename, sep="\t", index_col=0, header=0 +) # ## Format data for plotting @@ -140,44 +139,57 @@ # define plotting function -def plot_significance_vs_ranking(summary_df, method_name, x_label, output_figure_filename): +def plot_significance_vs_ranking( + summary_df, method_name, x_label, output_figure_filename +): # Format input dataframe plot_df = pd.DataFrame( - data={"Test statistic": summary_df[method_stats_dict[method_name]+" (Real)"].values, - "Percentile rank": summary_df["Rank (simulated)"].rank(pct=True).values - }, - index=summary_df.index + data={ + "Test statistic": summary_df[ + method_stats_dict[method_name] + " (Real)" + ].values, + "Percentile rank": summary_df["Rank (simulated)"].rank(pct=True).values, + }, + index=summary_df.index, ) - - fig = pn.ggplot(plot_df, pn.aes(x='Test statistic', y='Percentile rank')) + + fig = pn.ggplot(plot_df, pn.aes(x="Test statistic", y="Percentile rank")) fig += pn.geom_point() - fig += pn.geom_point(plot_df[plot_df['Percentile rank']>0.9], - pn.aes(x='Test statistic', y='Percentile rank'), - color='red' - ) - fig += pn.geom_text(pn.aes(label= - [x if plot_df.loc[x,'Percentile rank']>0.9 else "" for x in plot_df.index]), - ha='left', - va='top', - size=5 - ) - fig += pn.labs(x = x_label, - y = 'Percentile of ranking', - title = f'{method_name} pathway statistics vs ranking') + fig += pn.geom_point( + plot_df[plot_df["Percentile rank"] > 0.9], + pn.aes(x="Test statistic", y="Percentile rank"), + color="red", + ) + fig += pn.geom_text( + pn.aes( + label=[ + x if plot_df.loc[x, "Percentile rank"] > 0.9 else "" + for x in plot_df.index + ] + ), + ha="left", + va="top", + size=5, + ) + fig += pn.labs( + x=x_label, + y="Percentile of ranking", + title=f"{method_name} pathway statistics vs ranking", + ) fig += pn.theme_bw() fig += pn.theme( - legend_title_align = "center", - plot_background=pn.element_rect(fill='white'), - legend_key=pn.element_rect(fill='white', colour='white'), - legend_title=pn.element_text(family='sans-serif', size=15), - legend_text=pn.element_text(family='sans-serif', size=12), - plot_title=pn.element_text(family='sans-serif', size=15), - axis_text=pn.element_text(family='sans-serif', size=12), - axis_title=pn.element_text(family='sans-serif', size=15) - ) + legend_title_align="center", + plot_background=pn.element_rect(fill="white"), + legend_key=pn.element_rect(fill="white", colour="white"), + legend_title=pn.element_text(family="sans-serif", size=15), + legend_text=pn.element_text(family="sans-serif", size=12), + plot_title=pn.element_text(family="sans-serif", size=15), + axis_text=pn.element_text(family="sans-serif", size=12), + axis_title=pn.element_text(family="sans-serif", size=15), + ) print(fig) - + # Save figure fig.save( output_figure_filename, @@ -192,31 +204,41 @@ def plot_significance_vs_ranking(summary_df, method_name, x_label, output_figure # In[13]: -plot_significance_vs_ranking(gsea_pathway_summary, "GSEA", "adjusted p-value (BH)", "GSEA_pathway_ranking.svg") +plot_significance_vs_ranking( + gsea_pathway_summary, "GSEA", "adjusted p-value (BH)", "GSEA_pathway_ranking.svg" +) # In[14]: -plot_significance_vs_ranking(gsva_pathway_summary, "GSVA", "Enrichment score", "GSVA_pathway_ranking.svg") +plot_significance_vs_ranking( + gsva_pathway_summary, "GSVA", "Enrichment score", "GSVA_pathway_ranking.svg" +) # In[15]: -plot_significance_vs_ranking(roast_pathway_summary, "ROAST", "FDR (BH)", "ROAST_pathway_ranking.svg") +plot_significance_vs_ranking( + roast_pathway_summary, "ROAST", "FDR (BH)", "ROAST_pathway_ranking.svg" +) # In[16]: -plot_significance_vs_ranking(camera_pathway_summary, "CAMERA", "FDR (BH)", "CAMERA_pathway_ranking.svg") +plot_significance_vs_ranking( + camera_pathway_summary, "CAMERA", "FDR (BH)", "CAMERA_pathway_ranking.svg" +) # In[17]: -plot_significance_vs_ranking(ora_pathway_summary, "ORA", "adjusted p-value (BH)", "ORA_pathway_ranking.svg") +plot_significance_vs_ranking( + ora_pathway_summary, "ORA", "adjusted p-value (BH)", "ORA_pathway_ranking.svg" +) # **Takeaway:** diff --git a/pseudomonas_analysis/0_prepare_reference_gene_file.ipynb b/pseudomonas_analysis/0_prepare_reference_gene_file.ipynb new file mode 100644 index 00000000..7640c54e --- /dev/null +++ b/pseudomonas_analysis/0_prepare_reference_gene_file.ipynb @@ -0,0 +1,2456 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "# Prepare reference gene file\n", + "\n", + "This notebook creates a reference gene ranking file to use to compare SOPHIE generated gene ranking. The reference ranking information is obtained from [this repository](https://github.com/DartmouthStantonLab/GAPE). This [RDS object](https://github.com/DartmouthStantonLab/GAPE/blob/main/Pa_GPL84_refine_ANOVA_List_unzip.rds) contains 73 experiments. For each experiment, we will identify DEGs using log2FC > 1 and FDR < 0.05. We will rank genes by the proportion that they appeared as DE." + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "metadata": {}, + "outputs": [], + "source": [ + "%load_ext autoreload\n", + "%autoreload 2\n", + "\n", + "import os\n", + "import pandas as pd\n", + "import rpy2.robjects as ro\n", + "from rpy2.robjects import pandas2ri\n", + "from rpy2.robjects.conversion import localconverter\n", + "\n", + "from ponyo import utils" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "metadata": {}, + "outputs": [], + "source": [ + "# Read in config variables\n", + "base_dir = os.path.abspath(os.path.join(os.getcwd(),\"../\"))\n", + "\n", + "config_filename = os.path.abspath(os.path.join(base_dir,\n", + " \"configs\",\n", + " \"config_pseudomonas_33245.tsv\"))\n", + "params = utils.read_config(config_filename)" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "metadata": {}, + "outputs": [], + "source": [ + "# Load params\n", + "local_dir = params[\"local_dir\"]\n", + "reference_gene_filename = os.path.join(local_dir,\"Pa_GPL84_refine_ANOVA_List_unzip.rds\")" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "metadata": {}, + "outputs": [], + "source": [ + "readRDS = ro.r['readRDS']" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "metadata": {}, + "outputs": [], + "source": [ + "reference_Robject = readRDS(reference_gene_filename)" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/robjects/pandas2ri.py:191: FutureWarning: from_items is deprecated. Please use DataFrame.from_dict(dict(items), ...) instead. DataFrame.from_dict(OrderedDict(items)) may be used to preserve the key order.\n", + " res = PandasDataFrame.from_items(items)\n" + ] + }, + { + "data": { + "text/html": [ + "
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experiment_0experiment_1experiment_2experiment_3experiment_4experiment_5experiment_6experiment_7experiment_8experiment_9...experiment_63experiment_64experiment_65experiment_66experiment_67experiment_68experiment_69experiment_70experiment_71experiment_72
ProbeID
AFFX-Athal_GAPDH_at00000NaN00.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Athal_actin_at00000NaN00.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Athal_ubq_at000000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Bsubtilis_dapB_at101000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Bsubtilis_lys_at001000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Bsubtilis_pheB_at101000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Bsubtilis_thrC_at101000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-Bsubtilis_trpD_at00100NaN0NaN00.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-YEL002C_WPB1_at00000NaN0NaN0NaN...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-YEL018W_at00000NaN0NaN0NaN...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-YEL024W_RIP1_at00000NaN00.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-YER022W_SRB4_at00000NaN0NaN0NaN...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-YER148W_SPT15_at000000.00NaN00.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
AFFX-YFL039C_ACT1_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
PA0001_dnaA_at101001.000.011.0...00.01.00.00.00.00.00.00.01.0
PA0002_dnaN_at101000.000.011.0...00.01.00.00.00.00.00.00.00.0
PA0003_recF_at101001.000.011.0...00.01.00.00.00.00.00.00.01.0
PA0004_gyrB_at001000.000.000.0...00.01.00.00.00.00.00.00.01.0
PA0005_at001000.000.001.0...01.01.00.00.00.00.00.00.00.0
PA0006_at100000.000.011.0...01.00.00.00.00.00.00.00.00.0
PA0007_at001000.000.010.0...00.01.00.00.00.00.00.00.01.0
PA0008_glyS_at101000.000.000.0...01.01.01.00.00.00.00.00.01.0
PA0009_glyQ_at100101.010.011.0...01.01.01.00.00.00.00.00.01.0
PA0010_tag_at000000.000.000.0...00.0NaNNaN0.00.00.00.00.00.0
PA0011_at000000.000.001.0...00.00.00.00.00.00.00.00.00.0
PA0012_at100000.000.001.0...00.00.00.00.00.00.00.00.00.0
PA0013_at000000.000.001.0...00.01.00.00.00.00.00.00.00.0
PA0014_at000000.000.000.0...00.0NaNNaN0.00.00.00.0NaNNaN
PA0015_at000000.000.001.0...00.01.00.00.00.00.00.00.00.0
PA0016_trkA_at000000.000.001.0...00.01.00.00.00.00.00.00.00.0
..................................................................
ig_5991130_5992382_at100000.000.001.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_5992382_5991130_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_6090705_6092045_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_6092045_6090705_at000000.000.001.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_6125079_6125795_at001000.000.011.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_6125795_6125079_at101000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_629884_630527_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_630527_629884_at100000.000.001.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_64729_65339_at000000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_65339_64729_at000000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_65479_66303_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_66303_65479_at100000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_68616_69272_at100000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_69272_68616_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_721556_727608_s_at101100.010.011.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_727608_721556_s_at101000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_773696_774416_at000000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_774416_773696_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_785174_785969_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_785969_785174_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_788253_789144_at000000.000.001.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_789144_788253_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_863300_864095_at100000.000.011.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_864095_863300_at101000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_884172_884799_at001000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_884799_884172_at000000.000.010.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_901046_901934_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_901934_901046_at000000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_991198_991830_at000100.000.011.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
ig_991830_991198_at100000.000.000.0...0NaNNaNNaNNaNNaNNaNNaNNaNNaN
\n", + "

5900 rows × 73 columns

\n", + "
" + ], + "text/plain": [ + " experiment_0 experiment_1 experiment_2 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at 0 0 0 \n", + "AFFX-Athal_actin_at 0 0 0 \n", + "AFFX-Athal_ubq_at 0 0 0 \n", + "AFFX-Bsubtilis_dapB_at 1 0 1 \n", + "AFFX-Bsubtilis_lys_at 0 0 1 \n", + "AFFX-Bsubtilis_pheB_at 1 0 1 \n", + "AFFX-Bsubtilis_thrC_at 1 0 1 \n", + "AFFX-Bsubtilis_trpD_at 0 0 1 \n", + "AFFX-YEL002C_WPB1_at 0 0 0 \n", + "AFFX-YEL018W_at 0 0 0 \n", + "AFFX-YEL024W_RIP1_at 0 0 0 \n", + "AFFX-YER022W_SRB4_at 0 0 0 \n", + "AFFX-YER148W_SPT15_at 0 0 0 \n", + "AFFX-YFL039C_ACT1_at 0 0 0 \n", + "PA0001_dnaA_at 1 0 1 \n", + "PA0002_dnaN_at 1 0 1 \n", + "PA0003_recF_at 1 0 1 \n", + "PA0004_gyrB_at 0 0 1 \n", + "PA0005_at 0 0 1 \n", + "PA0006_at 1 0 0 \n", + "PA0007_at 0 0 1 \n", + "PA0008_glyS_at 1 0 1 \n", + "PA0009_glyQ_at 1 0 0 \n", + "PA0010_tag_at 0 0 0 \n", + "PA0011_at 0 0 0 \n", + "PA0012_at 1 0 0 \n", + "PA0013_at 0 0 0 \n", + "PA0014_at 0 0 0 \n", + "PA0015_at 0 0 0 \n", + "PA0016_trkA_at 0 0 0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at 1 0 0 \n", + "ig_5992382_5991130_at 0 0 0 \n", + "ig_6090705_6092045_at 0 0 0 \n", + "ig_6092045_6090705_at 0 0 0 \n", + "ig_6125079_6125795_at 0 0 1 \n", + "ig_6125795_6125079_at 1 0 1 \n", + "ig_629884_630527_at 0 0 0 \n", + "ig_630527_629884_at 1 0 0 \n", + "ig_64729_65339_at 0 0 0 \n", + "ig_65339_64729_at 0 0 0 \n", + "ig_65479_66303_at 0 0 0 \n", + "ig_66303_65479_at 1 0 0 \n", + "ig_68616_69272_at 1 0 0 \n", + "ig_69272_68616_at 0 0 0 \n", + "ig_721556_727608_s_at 1 0 1 \n", + "ig_727608_721556_s_at 1 0 1 \n", + "ig_773696_774416_at 0 0 0 \n", + "ig_774416_773696_at 0 0 0 \n", + "ig_785174_785969_at 0 0 0 \n", + "ig_785969_785174_at 0 0 0 \n", + "ig_788253_789144_at 0 0 0 \n", + "ig_789144_788253_at 0 0 0 \n", + "ig_863300_864095_at 1 0 0 \n", + "ig_864095_863300_at 1 0 1 \n", + "ig_884172_884799_at 0 0 1 \n", + "ig_884799_884172_at 0 0 0 \n", + "ig_901046_901934_at 0 0 0 \n", + "ig_901934_901046_at 0 0 0 \n", + "ig_991198_991830_at 0 0 0 \n", + "ig_991830_991198_at 1 0 0 \n", + "\n", + " experiment_3 experiment_4 experiment_5 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at 0 0 NaN \n", + "AFFX-Athal_actin_at 0 0 NaN \n", + "AFFX-Athal_ubq_at 0 0 0.0 \n", + "AFFX-Bsubtilis_dapB_at 0 0 0.0 \n", + "AFFX-Bsubtilis_lys_at 0 0 0.0 \n", + "AFFX-Bsubtilis_pheB_at 0 0 0.0 \n", + "AFFX-Bsubtilis_thrC_at 0 0 0.0 \n", + "AFFX-Bsubtilis_trpD_at 0 0 NaN \n", + "AFFX-YEL002C_WPB1_at 0 0 NaN \n", + "AFFX-YEL018W_at 0 0 NaN \n", + "AFFX-YEL024W_RIP1_at 0 0 NaN \n", + "AFFX-YER022W_SRB4_at 0 0 NaN \n", + "AFFX-YER148W_SPT15_at 0 0 0.0 \n", + "AFFX-YFL039C_ACT1_at 0 0 0.0 \n", + "PA0001_dnaA_at 0 0 1.0 \n", + "PA0002_dnaN_at 0 0 0.0 \n", + "PA0003_recF_at 0 0 1.0 \n", + "PA0004_gyrB_at 0 0 0.0 \n", + "PA0005_at 0 0 0.0 \n", + "PA0006_at 0 0 0.0 \n", + "PA0007_at 0 0 0.0 \n", + "PA0008_glyS_at 0 0 0.0 \n", + "PA0009_glyQ_at 1 0 1.0 \n", + "PA0010_tag_at 0 0 0.0 \n", + "PA0011_at 0 0 0.0 \n", + "PA0012_at 0 0 0.0 \n", + "PA0013_at 0 0 0.0 \n", + "PA0014_at 0 0 0.0 \n", + "PA0015_at 0 0 0.0 \n", + "PA0016_trkA_at 0 0 0.0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at 0 0 0.0 \n", + "ig_5992382_5991130_at 0 0 0.0 \n", + "ig_6090705_6092045_at 0 0 0.0 \n", + "ig_6092045_6090705_at 0 0 0.0 \n", + "ig_6125079_6125795_at 0 0 0.0 \n", + "ig_6125795_6125079_at 0 0 0.0 \n", + "ig_629884_630527_at 0 0 0.0 \n", + "ig_630527_629884_at 0 0 0.0 \n", + "ig_64729_65339_at 0 0 0.0 \n", + "ig_65339_64729_at 0 0 0.0 \n", + "ig_65479_66303_at 0 0 0.0 \n", + "ig_66303_65479_at 0 0 0.0 \n", + "ig_68616_69272_at 0 0 0.0 \n", + "ig_69272_68616_at 0 0 0.0 \n", + "ig_721556_727608_s_at 1 0 0.0 \n", + "ig_727608_721556_s_at 0 0 0.0 \n", + "ig_773696_774416_at 0 0 0.0 \n", + "ig_774416_773696_at 0 0 0.0 \n", + "ig_785174_785969_at 0 0 0.0 \n", + "ig_785969_785174_at 0 0 0.0 \n", + "ig_788253_789144_at 0 0 0.0 \n", + "ig_789144_788253_at 0 0 0.0 \n", + "ig_863300_864095_at 0 0 0.0 \n", + "ig_864095_863300_at 0 0 0.0 \n", + "ig_884172_884799_at 0 0 0.0 \n", + "ig_884799_884172_at 0 0 0.0 \n", + "ig_901046_901934_at 0 0 0.0 \n", + "ig_901934_901046_at 0 0 0.0 \n", + "ig_991198_991830_at 1 0 0.0 \n", + "ig_991830_991198_at 0 0 0.0 \n", + "\n", + " experiment_6 experiment_7 experiment_8 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at 0 0.0 0 \n", + "AFFX-Athal_actin_at 0 0.0 0 \n", + "AFFX-Athal_ubq_at 0 0.0 1 \n", + "AFFX-Bsubtilis_dapB_at 0 0.0 0 \n", + "AFFX-Bsubtilis_lys_at 0 0.0 1 \n", + "AFFX-Bsubtilis_pheB_at 0 0.0 0 \n", + "AFFX-Bsubtilis_thrC_at 0 0.0 0 \n", + "AFFX-Bsubtilis_trpD_at 0 NaN 0 \n", + "AFFX-YEL002C_WPB1_at 0 NaN 0 \n", + "AFFX-YEL018W_at 0 NaN 0 \n", + "AFFX-YEL024W_RIP1_at 0 0.0 1 \n", + "AFFX-YER022W_SRB4_at 0 NaN 0 \n", + "AFFX-YER148W_SPT15_at 0 NaN 0 \n", + "AFFX-YFL039C_ACT1_at 0 0.0 0 \n", + "PA0001_dnaA_at 0 0.0 1 \n", + "PA0002_dnaN_at 0 0.0 1 \n", + "PA0003_recF_at 0 0.0 1 \n", + "PA0004_gyrB_at 0 0.0 0 \n", + "PA0005_at 0 0.0 0 \n", + "PA0006_at 0 0.0 1 \n", + "PA0007_at 0 0.0 1 \n", + "PA0008_glyS_at 0 0.0 0 \n", + "PA0009_glyQ_at 1 0.0 1 \n", + "PA0010_tag_at 0 0.0 0 \n", + "PA0011_at 0 0.0 0 \n", + "PA0012_at 0 0.0 0 \n", + "PA0013_at 0 0.0 0 \n", + "PA0014_at 0 0.0 0 \n", + "PA0015_at 0 0.0 0 \n", + "PA0016_trkA_at 0 0.0 0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at 0 0.0 0 \n", + "ig_5992382_5991130_at 0 0.0 0 \n", + "ig_6090705_6092045_at 0 0.0 0 \n", + "ig_6092045_6090705_at 0 0.0 0 \n", + "ig_6125079_6125795_at 0 0.0 1 \n", + "ig_6125795_6125079_at 0 0.0 1 \n", + "ig_629884_630527_at 0 0.0 0 \n", + "ig_630527_629884_at 0 0.0 0 \n", + "ig_64729_65339_at 0 0.0 1 \n", + "ig_65339_64729_at 0 0.0 1 \n", + "ig_65479_66303_at 0 0.0 0 \n", + "ig_66303_65479_at 0 0.0 0 \n", + "ig_68616_69272_at 0 0.0 0 \n", + "ig_69272_68616_at 0 0.0 0 \n", + "ig_721556_727608_s_at 1 0.0 1 \n", + "ig_727608_721556_s_at 0 0.0 1 \n", + "ig_773696_774416_at 0 0.0 1 \n", + "ig_774416_773696_at 0 0.0 0 \n", + "ig_785174_785969_at 0 0.0 0 \n", + "ig_785969_785174_at 0 0.0 0 \n", + "ig_788253_789144_at 0 0.0 0 \n", + "ig_789144_788253_at 0 0.0 0 \n", + "ig_863300_864095_at 0 0.0 1 \n", + "ig_864095_863300_at 0 0.0 1 \n", + "ig_884172_884799_at 0 0.0 0 \n", + "ig_884799_884172_at 0 0.0 1 \n", + "ig_901046_901934_at 0 0.0 0 \n", + "ig_901934_901046_at 0 0.0 0 \n", + "ig_991198_991830_at 0 0.0 1 \n", + "ig_991830_991198_at 0 0.0 0 \n", + "\n", + " experiment_9 ... experiment_63 \\\n", + "ProbeID ... \n", + "AFFX-Athal_GAPDH_at 0.0 ... 0 \n", + "AFFX-Athal_actin_at 0.0 ... 0 \n", + "AFFX-Athal_ubq_at 0.0 ... 0 \n", + "AFFX-Bsubtilis_dapB_at 0.0 ... 0 \n", + "AFFX-Bsubtilis_lys_at 0.0 ... 0 \n", + "AFFX-Bsubtilis_pheB_at 0.0 ... 0 \n", + "AFFX-Bsubtilis_thrC_at 0.0 ... 0 \n", + "AFFX-Bsubtilis_trpD_at 0.0 ... 0 \n", + "AFFX-YEL002C_WPB1_at NaN ... 0 \n", + "AFFX-YEL018W_at NaN ... 0 \n", + "AFFX-YEL024W_RIP1_at 0.0 ... 0 \n", + "AFFX-YER022W_SRB4_at NaN ... 0 \n", + "AFFX-YER148W_SPT15_at 0.0 ... 0 \n", + "AFFX-YFL039C_ACT1_at 0.0 ... 0 \n", + "PA0001_dnaA_at 1.0 ... 0 \n", + "PA0002_dnaN_at 1.0 ... 0 \n", + "PA0003_recF_at 1.0 ... 0 \n", + "PA0004_gyrB_at 0.0 ... 0 \n", + "PA0005_at 1.0 ... 0 \n", + "PA0006_at 1.0 ... 0 \n", + "PA0007_at 0.0 ... 0 \n", + "PA0008_glyS_at 0.0 ... 0 \n", + "PA0009_glyQ_at 1.0 ... 0 \n", + "PA0010_tag_at 0.0 ... 0 \n", + "PA0011_at 1.0 ... 0 \n", + "PA0012_at 1.0 ... 0 \n", + "PA0013_at 1.0 ... 0 \n", + "PA0014_at 0.0 ... 0 \n", + "PA0015_at 1.0 ... 0 \n", + "PA0016_trkA_at 1.0 ... 0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at 1.0 ... 0 \n", + "ig_5992382_5991130_at 0.0 ... 0 \n", + "ig_6090705_6092045_at 0.0 ... 0 \n", + "ig_6092045_6090705_at 1.0 ... 0 \n", + "ig_6125079_6125795_at 1.0 ... 0 \n", + "ig_6125795_6125079_at 0.0 ... 0 \n", + "ig_629884_630527_at 0.0 ... 0 \n", + "ig_630527_629884_at 1.0 ... 0 \n", + "ig_64729_65339_at 0.0 ... 0 \n", + "ig_65339_64729_at 0.0 ... 0 \n", + "ig_65479_66303_at 0.0 ... 0 \n", + "ig_66303_65479_at 0.0 ... 0 \n", + "ig_68616_69272_at 0.0 ... 0 \n", + "ig_69272_68616_at 0.0 ... 0 \n", + "ig_721556_727608_s_at 1.0 ... 0 \n", + "ig_727608_721556_s_at 0.0 ... 0 \n", + "ig_773696_774416_at 0.0 ... 0 \n", + "ig_774416_773696_at 0.0 ... 0 \n", + "ig_785174_785969_at 0.0 ... 0 \n", + "ig_785969_785174_at 0.0 ... 0 \n", + "ig_788253_789144_at 1.0 ... 0 \n", + "ig_789144_788253_at 0.0 ... 0 \n", + "ig_863300_864095_at 1.0 ... 0 \n", + "ig_864095_863300_at 0.0 ... 0 \n", + "ig_884172_884799_at 0.0 ... 0 \n", + "ig_884799_884172_at 0.0 ... 0 \n", + "ig_901046_901934_at 0.0 ... 0 \n", + "ig_901934_901046_at 0.0 ... 0 \n", + "ig_991198_991830_at 1.0 ... 0 \n", + "ig_991830_991198_at 0.0 ... 0 \n", + "\n", + " experiment_64 experiment_65 experiment_66 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at NaN NaN NaN \n", + "AFFX-Athal_actin_at NaN NaN NaN \n", + "AFFX-Athal_ubq_at NaN NaN NaN \n", + "AFFX-Bsubtilis_dapB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_lys_at NaN NaN NaN \n", + "AFFX-Bsubtilis_pheB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_thrC_at NaN NaN NaN \n", + "AFFX-Bsubtilis_trpD_at NaN NaN NaN \n", + "AFFX-YEL002C_WPB1_at NaN NaN NaN \n", + "AFFX-YEL018W_at NaN NaN NaN \n", + "AFFX-YEL024W_RIP1_at NaN NaN NaN \n", + "AFFX-YER022W_SRB4_at NaN NaN NaN \n", + "AFFX-YER148W_SPT15_at NaN NaN NaN \n", + "AFFX-YFL039C_ACT1_at NaN NaN NaN \n", + "PA0001_dnaA_at 0.0 1.0 0.0 \n", + "PA0002_dnaN_at 0.0 1.0 0.0 \n", + "PA0003_recF_at 0.0 1.0 0.0 \n", + "PA0004_gyrB_at 0.0 1.0 0.0 \n", + "PA0005_at 1.0 1.0 0.0 \n", + "PA0006_at 1.0 0.0 0.0 \n", + "PA0007_at 0.0 1.0 0.0 \n", + "PA0008_glyS_at 1.0 1.0 1.0 \n", + "PA0009_glyQ_at 1.0 1.0 1.0 \n", + "PA0010_tag_at 0.0 NaN NaN \n", + "PA0011_at 0.0 0.0 0.0 \n", + "PA0012_at 0.0 0.0 0.0 \n", + "PA0013_at 0.0 1.0 0.0 \n", + "PA0014_at 0.0 NaN NaN \n", + "PA0015_at 0.0 1.0 0.0 \n", + "PA0016_trkA_at 0.0 1.0 0.0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at NaN NaN NaN \n", + "ig_5992382_5991130_at NaN NaN NaN \n", + "ig_6090705_6092045_at NaN NaN NaN \n", + "ig_6092045_6090705_at NaN NaN NaN \n", + "ig_6125079_6125795_at NaN NaN NaN \n", + "ig_6125795_6125079_at NaN NaN NaN \n", + "ig_629884_630527_at NaN NaN NaN \n", + "ig_630527_629884_at NaN NaN NaN \n", + "ig_64729_65339_at NaN NaN NaN \n", + "ig_65339_64729_at NaN NaN NaN \n", + "ig_65479_66303_at NaN NaN NaN \n", + "ig_66303_65479_at NaN NaN NaN \n", + "ig_68616_69272_at NaN NaN NaN \n", + "ig_69272_68616_at NaN NaN NaN \n", + "ig_721556_727608_s_at NaN NaN NaN \n", + "ig_727608_721556_s_at NaN NaN NaN \n", + "ig_773696_774416_at NaN NaN NaN \n", + "ig_774416_773696_at NaN NaN NaN \n", + "ig_785174_785969_at NaN NaN NaN \n", + "ig_785969_785174_at NaN NaN NaN \n", + "ig_788253_789144_at NaN NaN NaN \n", + "ig_789144_788253_at NaN NaN NaN \n", + "ig_863300_864095_at NaN NaN NaN \n", + "ig_864095_863300_at NaN NaN NaN \n", + "ig_884172_884799_at NaN NaN NaN \n", + "ig_884799_884172_at NaN NaN NaN \n", + "ig_901046_901934_at NaN NaN NaN \n", + "ig_901934_901046_at NaN NaN NaN \n", + "ig_991198_991830_at NaN NaN NaN \n", + "ig_991830_991198_at NaN NaN NaN \n", + "\n", + " experiment_67 experiment_68 experiment_69 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at NaN NaN NaN \n", + "AFFX-Athal_actin_at NaN NaN NaN \n", + "AFFX-Athal_ubq_at NaN NaN NaN \n", + "AFFX-Bsubtilis_dapB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_lys_at NaN NaN NaN \n", + "AFFX-Bsubtilis_pheB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_thrC_at NaN NaN NaN \n", + "AFFX-Bsubtilis_trpD_at NaN NaN NaN \n", + "AFFX-YEL002C_WPB1_at NaN NaN NaN \n", + "AFFX-YEL018W_at NaN NaN NaN \n", + "AFFX-YEL024W_RIP1_at NaN NaN NaN \n", + "AFFX-YER022W_SRB4_at NaN NaN NaN \n", + "AFFX-YER148W_SPT15_at NaN NaN NaN \n", + "AFFX-YFL039C_ACT1_at NaN NaN NaN \n", + "PA0001_dnaA_at 0.0 0.0 0.0 \n", + "PA0002_dnaN_at 0.0 0.0 0.0 \n", + "PA0003_recF_at 0.0 0.0 0.0 \n", + "PA0004_gyrB_at 0.0 0.0 0.0 \n", + "PA0005_at 0.0 0.0 0.0 \n", + "PA0006_at 0.0 0.0 0.0 \n", + "PA0007_at 0.0 0.0 0.0 \n", + "PA0008_glyS_at 0.0 0.0 0.0 \n", + "PA0009_glyQ_at 0.0 0.0 0.0 \n", + "PA0010_tag_at 0.0 0.0 0.0 \n", + "PA0011_at 0.0 0.0 0.0 \n", + "PA0012_at 0.0 0.0 0.0 \n", + "PA0013_at 0.0 0.0 0.0 \n", + "PA0014_at 0.0 0.0 0.0 \n", + "PA0015_at 0.0 0.0 0.0 \n", + "PA0016_trkA_at 0.0 0.0 0.0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at NaN NaN NaN \n", + "ig_5992382_5991130_at NaN NaN NaN \n", + "ig_6090705_6092045_at NaN NaN NaN \n", + "ig_6092045_6090705_at NaN NaN NaN \n", + "ig_6125079_6125795_at NaN NaN NaN \n", + "ig_6125795_6125079_at NaN NaN NaN \n", + "ig_629884_630527_at NaN NaN NaN \n", + "ig_630527_629884_at NaN NaN NaN \n", + "ig_64729_65339_at NaN NaN NaN \n", + "ig_65339_64729_at NaN NaN NaN \n", + "ig_65479_66303_at NaN NaN NaN \n", + "ig_66303_65479_at NaN NaN NaN \n", + "ig_68616_69272_at NaN NaN NaN \n", + "ig_69272_68616_at NaN NaN NaN \n", + "ig_721556_727608_s_at NaN NaN NaN \n", + "ig_727608_721556_s_at NaN NaN NaN \n", + "ig_773696_774416_at NaN NaN NaN \n", + "ig_774416_773696_at NaN NaN NaN \n", + "ig_785174_785969_at NaN NaN NaN \n", + "ig_785969_785174_at NaN NaN NaN \n", + "ig_788253_789144_at NaN NaN NaN \n", + "ig_789144_788253_at NaN NaN NaN \n", + "ig_863300_864095_at NaN NaN NaN \n", + "ig_864095_863300_at NaN NaN NaN \n", + "ig_884172_884799_at NaN NaN NaN \n", + "ig_884799_884172_at NaN NaN NaN \n", + "ig_901046_901934_at NaN NaN NaN \n", + "ig_901934_901046_at NaN NaN NaN \n", + "ig_991198_991830_at NaN NaN NaN \n", + "ig_991830_991198_at NaN NaN NaN \n", + "\n", + " experiment_70 experiment_71 experiment_72 \n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at NaN NaN NaN \n", + "AFFX-Athal_actin_at NaN NaN NaN \n", + "AFFX-Athal_ubq_at NaN NaN NaN \n", + "AFFX-Bsubtilis_dapB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_lys_at NaN NaN NaN \n", + "AFFX-Bsubtilis_pheB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_thrC_at NaN NaN NaN \n", + "AFFX-Bsubtilis_trpD_at NaN NaN NaN \n", + "AFFX-YEL002C_WPB1_at NaN NaN NaN \n", + "AFFX-YEL018W_at NaN NaN NaN \n", + "AFFX-YEL024W_RIP1_at NaN NaN NaN \n", + "AFFX-YER022W_SRB4_at NaN NaN NaN \n", + "AFFX-YER148W_SPT15_at NaN NaN NaN \n", + "AFFX-YFL039C_ACT1_at NaN NaN NaN \n", + "PA0001_dnaA_at 0.0 0.0 1.0 \n", + "PA0002_dnaN_at 0.0 0.0 0.0 \n", + "PA0003_recF_at 0.0 0.0 1.0 \n", + "PA0004_gyrB_at 0.0 0.0 1.0 \n", + "PA0005_at 0.0 0.0 0.0 \n", + "PA0006_at 0.0 0.0 0.0 \n", + "PA0007_at 0.0 0.0 1.0 \n", + "PA0008_glyS_at 0.0 0.0 1.0 \n", + "PA0009_glyQ_at 0.0 0.0 1.0 \n", + "PA0010_tag_at 0.0 0.0 0.0 \n", + "PA0011_at 0.0 0.0 0.0 \n", + "PA0012_at 0.0 0.0 0.0 \n", + "PA0013_at 0.0 0.0 0.0 \n", + "PA0014_at 0.0 NaN NaN \n", + "PA0015_at 0.0 0.0 0.0 \n", + "PA0016_trkA_at 0.0 0.0 0.0 \n", + "... ... ... ... \n", + "ig_5991130_5992382_at NaN NaN NaN \n", + "ig_5992382_5991130_at NaN NaN NaN \n", + "ig_6090705_6092045_at NaN NaN NaN \n", + "ig_6092045_6090705_at NaN NaN NaN \n", + "ig_6125079_6125795_at NaN NaN NaN \n", + "ig_6125795_6125079_at NaN NaN NaN \n", + "ig_629884_630527_at NaN NaN NaN \n", + "ig_630527_629884_at NaN NaN NaN \n", + "ig_64729_65339_at NaN NaN NaN \n", + "ig_65339_64729_at NaN NaN NaN \n", + "ig_65479_66303_at NaN NaN NaN \n", + "ig_66303_65479_at NaN NaN NaN \n", + "ig_68616_69272_at NaN NaN NaN \n", + "ig_69272_68616_at NaN NaN NaN \n", + "ig_721556_727608_s_at NaN NaN NaN \n", + "ig_727608_721556_s_at NaN NaN NaN \n", + "ig_773696_774416_at NaN NaN NaN \n", + "ig_774416_773696_at NaN NaN NaN \n", + "ig_785174_785969_at NaN NaN NaN \n", + "ig_785969_785174_at NaN NaN NaN \n", + "ig_788253_789144_at NaN NaN NaN \n", + "ig_789144_788253_at NaN NaN NaN \n", + "ig_863300_864095_at NaN NaN NaN \n", + "ig_864095_863300_at NaN NaN NaN \n", + "ig_884172_884799_at NaN NaN NaN \n", + "ig_884799_884172_at NaN NaN NaN \n", + "ig_901046_901934_at NaN NaN NaN \n", + "ig_901934_901046_at NaN NaN NaN \n", + "ig_991198_991830_at NaN NaN NaN \n", + "ig_991830_991198_at NaN NaN NaN \n", + "\n", + "[5900 rows x 73 columns]" + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# For each experiment get df\n", + "# For each df, if label gene as DEGs based on log2FC>1 and FDR<0.05\n", + "# Concatenate series\n", + "num_experiments = len(reference_Robject)\n", + "reference_stats_df = pd.DataFrame()\n", + "\n", + "for i in range(num_experiments):\n", + " # Get df for experiment\n", + " reference_df = pandas2ri.ri2py(reference_Robject[i])\n", + " \n", + " reference_df = reference_df.set_index(\"ProbeID\")\n", + " \n", + " # Find DEGs\n", + " degs_ids = list(reference_df[(abs(reference_df[\"Log2FC\"])>1) & (reference_df[\"FDR\"]<0.05)].index)\n", + " reference_df[\"DEG\"] = 0\n", + " reference_df.loc[degs_ids, \"DEG\"] = 1\n", + " \n", + " # Create df with labels for if gene is DE or not\n", + " if i == 0:\n", + " reference_stats_df = reference_df[\"DEG\"].to_frame(\"experiment_0\") \n", + " else:\n", + " reference_stats_df = pd.merge(\n", + " reference_stats_df,\n", + " reference_df[\"DEG\"].to_frame(f\"experiment_{i}\"),\n", + " left_index=True, \n", + " right_index=True,\n", + " how='left'\n", + " )\n", + "reference_stats_df " + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "metadata": { + "scrolled": true + }, + "outputs": [], + "source": [ + "# Map `ProbeID` to `IntergenicSpotID` that contains PA#### IDs\n", + "example_reference_df = pandas2ri.ri2py(reference_Robject[0])\n", + "example_reference_df.set_index(\"ProbeID\", inplace=True)\n", + "\n", + "merged_df = pd.merge(reference_stats_df, example_reference_df, left_index=True, right_index=True)\n", + "\n", + "# Get relevant columns (`IntergenicSpotID` and `experiment_*`)\n", + "experiment_cols = [col for col in merged_df.columns if 'experiment_' in col]\n", + "merged_df = merged_df[experiment_cols]\n", + "\n", + "# Aggregate to get ranking of genes\n", + "merged_df[\"prop DEGs\"] = merged_df.sum(axis=1)/num_experiments" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "metadata": {}, + "outputs": [], + "source": [ + "# Extract PA#### ids from `ProbeID`\n", + "# This will be used to compare against SOPHIE ranked genes\n", + "pao1_ids = [str_ls[0] for str_ls in merged_df.index.str.split(\"_\")]\n", + "merged_df[\"gene id\"] = pao1_ids" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "data": { + "text/html": [ + "
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AFFX-Athal_actin_at00000NaN00.000.0...NaNNaNNaNNaNNaNNaNNaNNaN0.082192AFFX-Athal
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NaN \n", + "\n", + " experiment_66 experiment_67 experiment_68 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at NaN NaN NaN \n", + "AFFX-Athal_actin_at NaN NaN NaN \n", + "AFFX-Athal_ubq_at NaN NaN NaN \n", + "AFFX-Bsubtilis_dapB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_lys_at NaN NaN NaN \n", + "\n", + " experiment_69 experiment_70 experiment_71 \\\n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at NaN NaN NaN \n", + "AFFX-Athal_actin_at NaN NaN NaN \n", + "AFFX-Athal_ubq_at NaN NaN NaN \n", + "AFFX-Bsubtilis_dapB_at NaN NaN NaN \n", + "AFFX-Bsubtilis_lys_at NaN NaN NaN \n", + "\n", + " experiment_72 prop DEGs gene id \n", + "ProbeID \n", + "AFFX-Athal_GAPDH_at NaN 0.082192 AFFX-Athal \n", + "AFFX-Athal_actin_at NaN 0.082192 AFFX-Athal \n", + "AFFX-Athal_ubq_at NaN 0.095890 AFFX-Athal \n", + "AFFX-Bsubtilis_dapB_at NaN 0.150685 AFFX-Bsubtilis \n", + "AFFX-Bsubtilis_lys_at NaN 0.164384 AFFX-Bsubtilis \n", + "\n", + "[5 rows x 75 columns]" + ] + }, + "execution_count": 9, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "merged_df.head()" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "metadata": {}, + "outputs": [], + "source": [ + "# Save file\n", + "# Here are the names that we will use for the comparison in notebook 2_identify_generic_genes_pathways.ipynb\n", + "# DE_prior_filename = output_filename\n", + "# ref_gene_col = \"gene id\"\n", + "# ref_rank_col = \"prop DEGs\"\n", + "merged_df.to_csv('GAPE_proportions.txt', sep=\"\\t\")" + ] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python [conda env:generic_expression] *", + "language": "python", + "name": "conda-env-generic_expression-py" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.7.9" + } + }, + "nbformat": 4, + "nbformat_minor": 4 +} diff --git a/pseudomonas_analysis/0_subset_training_compendium.ipynb b/pseudomonas_analysis/0_subset_training_compendium.ipynb new file mode 100644 index 00000000..07934a34 --- /dev/null +++ b/pseudomonas_analysis/0_subset_training_compendium.ipynb @@ -0,0 +1,2899 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "# Subset training compendium\n", + "\n", + "This notebook subsets the normalized compendium to only include those samples that use PAO1 strains. This filtered training compendium will be used to examine the hypothesis that the subset of genes that are found to be generic by SOPHIE are not generic using GAPE-curated experiments because SOPHIE is trained on a compendium containing multiple strains, whereas we suspect that the GAPE experiments are only from a single strain (PAO1). So genes that are generic in other strain contexts will not be detected by GAPE." + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "metadata": { + "scrolled": false + }, + "outputs": [], + "source": [ + "%load_ext autoreload\n", + "%autoreload 2\n", + "\n", + "import os\n", + "import sys\n", + "import pandas as pd\n", + "\n", + "from ponyo import utils" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Set parameters for data processing\n", + "\n", + "Most parameters are read from `config_filename`. " + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "metadata": {}, + "outputs": [], + "source": [ + "base_dir = os.path.abspath(os.path.join(os.getcwd(), \"../\"))\n", + "\n", + "# Read in config variables\n", + "config_filename = os.path.abspath(\n", + " os.path.join(base_dir, \"configs\", \"config_pseudomonas_pao1.tsv\")\n", + ")\n", + "\n", + "params = utils.read_config(config_filename)\n", + "\n", + "local_dir = params[\"local_dir\"]\n", + "dataset_name = params[\"dataset_name\"]\n", + "project_id = params['project_id']\n", + "raw_compendium_filename = \"https://raw.githubusercontent.com/greenelab/adage/master/Data_collection_processing/Pa_compendium_02.22.2014.pcl\"\n", + "\n", + "# Load metadata file with annotations per sample\n", + "metadata_filename = os.path.join(\n", + " base_dir,\n", + " dataset_name,\n", + " \"data\",\n", + " \"metadata\",\n", + " \"sample_annotations.tsv\")\n", + "\n", + "# Load metadata file with annotations per sample\n", + "sample_id_filename = os.path.join(\n", + " base_dir,\n", + " dataset_name,\n", + " \"data\",\n", + " \"metadata\",\n", + " f\"{project_id}_process_samples.tsv\")\n", + "\n", + "# Output filename\n", + "out_compendium_filename = params[\"raw_compendium_filename\"]" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## Read data and metadata" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "metadata": {}, + "outputs": [], + "source": [ + "# Read normalized compendium\n", + "raw_compendium = pd.read_csv(raw_compendium_filename, sep=\"\\t\", index_col=0, header=0).T\n", + "\n", + "# Read metadata file\n", + "metadata = pd.read_csv(metadata_filename, sep=\"\\t\", index_col=0, header=0)\n", + "\n", + "# Read sample id file\n", + "project_sample_ids = pd.read_csv(sample_id_filename, sep=\"\\t\", index_col=None, header=0)" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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experiment
E-GEOD-46947GSM1141730 1GSM1141730_PA01_ZnO_PZO_.CELPseudomonas aeruginosa PAO1 LB aerated 5 h wi...RNALBNaNNaNplanktonicaeratedPAO137.01 mM ZnO nanoparticlesGrown for 5hNaNNaNNaNNaN
E-GEOD-46947GSM1141729 1GSM1141729_PA01_none_PC_.CELPseudomonas aeruginosa PAO1 LB aerated 5 hRNALBNaNNaNplanktonicaeratedPAO137.0NaNGrown for 5hNaNNaNNaNNaN
E-GEOD-65882GSM1608059 1GSM1608059_Planktonic_1.CELPAO1 WT. Planktonic. Rep1RNAPBM plus 1 g / L glucose.WT0.26PlanktonicAeratedPAO137.0NaNGrown shaking at 200rpmNaNNaNNaNNaN
E-GEOD-65882GSM1608060 1GSM1608060_Planktonic_2.CELPAO1 WT. Planktonic. Rep2RNAPBM plus 1 g / L glucose.WT0.26PlanktonicAeratedPAO137.0NaNGrown shaking at 200rpmNaNNaNNaNNaN
E-GEOD-65882GSM1608061 1GSM1608061_Planktonic_3.CELPAO1 WT. Planktonic. Rep3RNAPBM plus 1 g / L glucose.WT0.26PlanktonicAeratedPAO137.0NaNGrown shaking at 200rpmNaNNaNNaNNaN
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" + ], + "text/plain": [ + " sample_name ml_data_source \\\n", + "experiment \n", + "E-GEOD-46947 GSM1141730 1 GSM1141730_PA01_ZnO_PZO_.CEL \n", + "E-GEOD-46947 GSM1141729 1 GSM1141729_PA01_none_PC_.CEL \n", + "E-GEOD-65882 GSM1608059 1 GSM1608059_Planktonic_1.CEL \n", + "E-GEOD-65882 GSM1608060 1 GSM1608060_Planktonic_2.CEL \n", + "E-GEOD-65882 GSM1608061 1 GSM1608061_Planktonic_3.CEL \n", + "\n", + " description nucleic_acid \\\n", + "experiment \n", + "E-GEOD-46947 Pseudomonas aeruginosa PAO1 LB aerated 5 h wi... RNA \n", + "E-GEOD-46947 Pseudomonas aeruginosa PAO1 LB aerated 5 h RNA \n", + "E-GEOD-65882 PAO1 WT. Planktonic. Rep1 RNA \n", + "E-GEOD-65882 PAO1 WT. Planktonic. Rep2 RNA \n", + "E-GEOD-65882 PAO1 WT. Planktonic. Rep3 RNA \n", + "\n", + " medium genotype od growth_setting_1 \\\n", + "experiment \n", + "E-GEOD-46947 LB NaN NaN planktonic \n", + "E-GEOD-46947 LB NaN NaN planktonic \n", + "E-GEOD-65882 PBM plus 1 g / L glucose. WT 0.26 Planktonic \n", + "E-GEOD-65882 PBM plus 1 g / L glucose. WT 0.26 Planktonic \n", + "E-GEOD-65882 PBM plus 1 g / L glucose. WT 0.26 Planktonic \n", + "\n", + " growth_setting_2 strain temperature treatment \\\n", + "experiment \n", + "E-GEOD-46947 aerated PAO1 37.0 1 mM ZnO nanoparticles \n", + "E-GEOD-46947 aerated PAO1 37.0 NaN \n", + "E-GEOD-65882 Aerated PAO1 37.0 NaN \n", + "E-GEOD-65882 Aerated PAO1 37.0 NaN \n", + "E-GEOD-65882 Aerated PAO1 37.0 NaN \n", + "\n", + " additional_notes variant_phenotype abx_marker \\\n", + "experiment \n", + "E-GEOD-46947 Grown for 5h NaN NaN \n", + "E-GEOD-46947 Grown for 5h NaN NaN \n", + "E-GEOD-65882 Grown shaking at 200rpm NaN NaN \n", + "E-GEOD-65882 Grown shaking at 200rpm NaN NaN \n", + "E-GEOD-65882 Grown shaking at 200rpm NaN NaN \n", + "\n", + " biotic_int_lv_2 biotic_int_lv_1 \n", + "experiment \n", + "E-GEOD-46947 NaN NaN \n", + "E-GEOD-46947 NaN NaN \n", + "E-GEOD-65882 NaN NaN \n", + "E-GEOD-65882 NaN NaN \n", + "E-GEOD-65882 NaN NaN " + ] + }, + "execution_count": 5, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "metadata.head()" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "metadata": {}, + "outputs": [], + "source": [ + "# Get sample ids that have PAO1 strain\n", + "pao1_metadata = metadata.loc[metadata[\"strain\"].str.contains(\"PAO1\")]\n", + "experiment_ids = list(pao1_metadata.index)\n", + "\n", + "assert \"E-GEOD-33245\" in experiment_ids" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "719\n" + ] + }, + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/ipykernel_launcher.py:5: FutureWarning: \n", + "Passing list-likes to .loc or [] with any missing label will raise\n", + "KeyError in the future, you can use .reindex() as an alternative.\n", + "\n", + "See the documentation here:\n", + "https://pandas.pydata.org/pandas-docs/stable/indexing.html#deprecate-loc-reindex-listlike\n", + " \"\"\"\n" + ] + } + ], + "source": [ + "# Get normalized data associated with PAO1 sample ids\n", + "pao1_sample_ids = list(pao1_metadata[\"ml_data_source\"])\n", + "print(len(pao1_sample_ids))\n", + "\n", + "pao1_raw_compendium = raw_compendium.loc[pao1_sample_ids]\n", + "\n", + "assert len(pao1_sample_ids) == pao1_raw_compendium.shape[0]" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "(545, 5549)\n" + ] + }, + { + "data": { + "text/html": [ + "
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PA0001PA0002PA0003PA0004PA0005PA0006PA0007PA0008PA0009PA0010...PA5561PA5562PA5563PA5564PA5565PA5566PA5567PA5568PA5569PA5570
GSM1146022_pJN105_1.CEL9.46963010.1706148.4685169.5856628.3538238.4525497.3548459.9135608.2584235.445693...8.7905379.8356839.6526319.8873779.9193756.3688288.23368011.34642412.36457912.116378
GSM1146023_pJN105_2.CEL9.6176349.5395549.9222379.1699498.0719169.2386277.9239889.5085168.1744576.206660...7.95766810.3904679.52162110.2929279.6163516.8181727.23689711.26916811.29284310.810757
GSM1146024_phaF_1.CEL9.65021210.4897988.5207059.0665608.2721588.4765156.8458839.7771218.0301935.532491...8.8729889.8327819.71271410.32782010.4017506.8252568.15712711.20432812.35618611.888967
GSM1146025_phaF_2.CEL9.4503089.9211778.4658999.7419618.7590618.2024947.6256429.6106238.0686575.538607...8.7632099.71093510.01333110.4073979.9062226.5020367.50964311.23400612.49740212.137581
GSM1244967_PAO1-22-replicate-01.CEL9.0492579.9271438.8855478.8046605.9881857.7644618.3502827.7741657.7741055.510923...9.3563317.3778229.6446717.4291567.6549366.1319656.2412177.6841219.07284510.695175
GSM1244968_PAO1-22-replicate-02.CEL8.8331679.9170359.0096818.9008526.0964027.7491638.3197738.3013157.6007335.706577...9.4860766.8943969.7230227.7885557.6052156.2310416.3032517.8154128.89642210.714222
GSM1244969_PAO1-22-replicate-03.CEL8.8846479.9073168.7377928.6287586.2700977.9893378.3047877.9536467.6948895.679747...9.0803177.2969799.6559507.3458367.6593055.7027646.3904297.8639969.19642610.671757
GSM1244970_PAO1-37-replicate-01.CEL8.7783519.8724378.7551268.6620067.2129518.4263008.6701888.6534057.7375665.695070...9.1534017.9277849.5727308.2849338.5807995.9597426.2659077.82412310.90782612.177075
GSM1244971_PAO1-37-replicate-02.CEL9.0612439.8281948.3422998.8420266.4658547.9701518.4321608.2267107.8774925.785088...9.3374088.0132159.5533628.5906368.6289735.7787916.8307938.05258110.92972812.152272
GSM1244972_PAO1-37-replicate-03.CEL8.80854110.1657038.6279648.6891086.9057498.3066358.7809968.5677397.1905085.742351...9.0133577.8402259.4059218.2081018.4802496.2327565.9919887.84881810.87920712.175344
GSM1237734_M9_H103_2_51059600653056031211409890238138.CEL9.27164111.1148598.5525509.7829056.9936707.0259528.4127869.0283187.9187875.318933...6.2213709.0413288.9889238.7425188.5584205.9195846.9720509.09367810.6111499.728216
GSM1237735_M9_H103_3_51059600653061050411410396750551.CEL9.17154710.7477648.6582479.7298177.4565657.5520168.1201018.3771448.2512626.064736...6.2249908.7955728.9143578.1246178.2610415.6375277.0711459.10748310.94990510.030924
GSM1237736_M9_H103_4_51059600653061050411410396750502.CEL8.98264811.0294258.52102510.0754776.9106206.9656777.9339839.3058588.3605025.381044...6.5023239.0453918.7379198.7925148.7691015.6820876.94492610.14943911.31028010.723607
GSM1237737_M9_PAOSX_1_51059600653060050411410396750419.CEL9.03459110.7863228.8424369.7279457.2938837.5588817.8067458.7054498.0994935.903732...6.7253959.1297169.2005218.4753978.4416875.3570087.1731809.41246111.13020410.392338
GSM1237738_M9_PAOSX_3_51059600653060050411410396750359.CEL9.03370510.7429488.6993029.7838817.0612877.5371237.7115498.5416487.8074245.775868...6.2064609.1373839.1277858.6264488.1501205.7104507.1226269.20567811.07061910.266992
GSM1237739_M9_PAOSX_4_51059600653061050411410396750526.CEL9.06442710.8323328.6060149.8921756.8648367.4529937.7226049.0193127.8548755.668111...6.3827249.2477748.8358998.8424978.5071055.5503157.1408909.83535211.12938410.490768
Overhage11002_Pae_G1a.CEL9.06071210.2590158.3328788.9399227.0652057.1841867.0389948.7210538.3570725.635459...8.1019309.1152859.7000318.4351658.5638725.5007477.0724238.85531511.03908910.343857
Overhage5002_Pae_G1a.CEL8.62604110.3675438.4402879.1128227.1701587.1234397.1957228.4464538.3801965.632470...7.8708868.7430709.6387688.4507618.6042905.2313236.9741588.80804710.95083310.236251
Overhage11001_Pae_G1a.CEL9.00724010.4514538.2638568.9228517.2076947.1358237.3282888.6422038.3618545.674192...7.6764978.7565069.4126068.2806518.7143535.5114987.0593348.42905611.18087110.486374
Overhage5001_Pae_G1a.CEL9.03442810.1334788.1535308.8428777.0044187.4128376.9651117.9224888.2465816.276085...8.2362828.5282019.4732958.1534238.5641075.6562816.9662648.38000311.01923410.340256
GSM838206_OXYR-LB-1_Pae_G1a.CEL8.6061209.8021258.1964617.9215766.6713957.3367878.0925818.1139937.8457905.535163...8.2037188.8028669.1537778.5037788.7163925.9596627.0034278.48545810.92667510.660376
GSM838207_OXYR-LB-2_Pae_G1a.CEL8.4445319.6196428.5162018.2527606.7611137.6662288.6013318.0491117.7561015.414321...8.1512668.7632608.9331478.4376758.3131805.8671246.9687978.44286210.75823510.065086
GSM838208_OXYR-LB-4_Pae_G1a.CEL8.3532729.7066098.1874298.3525296.8086347.3796578.1828898.1057837.8847375.563755...7.7507338.7407949.0179178.5402828.7848155.8989046.9971148.85543810.91804410.539477
GSM838209_OXYR-PM-1_Pae_G1a.CEL9.0577509.7501998.4993868.8212728.3114688.4583947.8452867.9465177.7440255.238127...8.0376248.4580808.9611759.2208589.4415215.8487127.4677318.53088110.59074610.163238
GSM838210_OXYR-PM-3_Pae_G1a.CEL8.6350899.5300698.3096978.4867518.2712488.1219018.0175217.6838637.9185445.343945...8.7552848.4597988.7838039.0587169.3502705.7484157.2647328.52551010.71766910.294786
GSM838211_OXYR-PM-4_Pae_G1a.CEL8.6753089.6653088.2360438.2847948.4734357.8938567.9953047.8376667.5625245.325558...8.3539078.4931698.8513539.1142609.4336965.9352607.5129518.30309710.68911710.221476
GSM838212_PAO1-LB-1_Pae_G1a.CEL8.5931109.8941538.2339668.4832116.7892847.6775937.7136118.2843967.6073645.669414...7.9444818.8304449.1051218.8518298.6669965.8127967.0180618.77742210.94341311.017426
GSM838213_PAO1-LB-2_Pae_G1a.CEL8.5401649.9969127.9605488.4962867.2271487.7481057.7877478.5044867.6130455.490780...7.5065988.8385469.0091898.9357178.7503145.7917076.8179438.47452410.89014710.733528
GSM838214_PAO1-LB-3_Pae_G1a.CEL8.5429639.9056278.4460558.6093607.0333187.5216987.8765828.3893267.6729615.450242...7.5670198.8368208.9269118.9347008.7340475.8190907.0981238.78814911.24691311.015347
GSM838215_PAO1-PM-1_Pae_G1a.CEL9.1835199.9302408.3516809.0653648.3140308.4850597.9193018.2961468.1927195.556262...8.7429388.5904899.2591799.7844029.8902945.5996927.8616799.02079311.34109510.742094
..................................................................
GSM267256.CEL8.2366869.9053668.1271488.5548666.9581017.1677288.0831328.2084697.6391265.580815...6.6908648.8137838.7974948.1204538.4860737.1335007.2359469.5211729.9607508.022413
GSM267257.CEL7.8059269.5772888.1712778.5289947.1053807.1101717.6753628.7152547.5980915.470109...6.7298888.8122758.4299318.4522668.5913137.2670377.33266210.00928710.1393087.958096
GSM267258.CEL8.38898910.1207698.1055078.8424706.4965346.8824918.0885478.3426537.8215895.506512...6.8236888.7635808.6308328.3017058.4146366.1227167.3722829.39356510.4252839.132786
GSM267259.CEL8.50246910.1516187.9326699.1912586.7970577.0404348.0011348.4561958.0699835.492802...6.7228478.6510579.0761408.2697938.7621856.7906177.4701219.30888910.3663158.997943
54375-4-05.CEL9.32799610.7819779.16998810.2692397.2379997.6637586.8551949.6315739.4044655.684067...7.1277369.68760710.1996129.4571529.3183725.5238987.91103110.82827111.59764311.268520
dPA54375-18-05.CEL9.42851410.6328368.8748669.8167397.4892147.8496777.2641329.5263869.5354935.708800...7.2957119.97715910.1303149.3723209.3926645.6501187.85425811.03539011.26767910.867690
WT12935-4-05.CEL9.26680210.7120178.98623710.4221007.2847217.9947357.3283129.5963459.3734945.720567...6.9681919.76120910.1182239.6924809.0260635.8682797.71524510.94919411.27136310.732218
WT12935-18-05.CEL9.20489710.4820598.7430519.8242237.5074307.6458027.1716559.7499209.4680675.660903...6.7167689.88032110.3411499.7624069.2366565.7802087.76567211.27784611.35295010.970310
GSM234928.CEL8.98862310.3492788.4326008.7659756.6211277.1665718.1954698.9229258.4388465.363427...7.5453258.8492449.0636138.7460168.5805396.3983337.9060969.77138910.7474018.877742
GSM234929.CEL7.6033898.9584217.9052647.8083086.7699427.2717527.5571908.6464907.8246075.623979...6.6590958.6247608.5602438.6626938.4270617.7220398.61472910.12110810.1665606.876660
GSM199982.CEL8.63605110.0640338.3805189.0619476.7952026.7842508.8338688.1073498.0271425.205947...6.0140548.8990338.7449488.0418668.4297725.8310187.0874979.16029810.2337298.417952
GSM199983.CEL8.49145210.1352008.4104869.1590026.6675186.7634489.0270418.4176498.0763625.140327...6.3178308.5271908.7055858.0789228.3017345.8574626.6505178.99275710.2816898.721675
GSM199984.CEL8.26399910.3556268.3989469.4690576.9638057.2630578.9285768.6337718.0457495.154168...6.1329918.3278178.4998798.2360258.1397406.5234336.9255619.28154710.4209448.622205
GSM199985.CEL8.34774610.3044448.4240559.2344256.8365577.0777128.4805918.6690577.9304135.375658...6.4872838.6636768.6790608.1303658.4232686.1117597.0115679.44847010.5380098.674091
GSM199986.CEL8.40366910.4774288.3477299.1997356.6702367.2058988.1979888.4965368.1704605.307389...5.9677118.5905098.7306278.2464118.1961666.1246996.8339999.14537810.3726008.760325
MSC_01.CEL9.80810511.10974210.1923919.9071588.0061058.1871947.3105989.90076210.1219965.474449...8.4217339.93445110.33926810.39538610.4175385.5873948.36362811.08787912.21300911.736927
MSC_02.CEL9.69963310.5983069.8949679.7554818.2887437.9611037.3118349.9910519.7564185.468767...7.9204969.75302310.30384810.42750510.1521295.6892947.91964511.23258212.36147111.974702
MSC_03.CEL9.64353010.8941129.8621159.8500278.1304367.7710437.40075110.4379019.9130655.581816...7.1811299.92476810.68234310.74271610.1797965.9017958.02301111.50434412.24610911.354957
MSC_04.CEL9.65167510.7931219.7238669.8894588.1443027.8336347.1039819.9665219.7803875.466294...7.5074059.78784110.04551110.3355459.8378405.5848167.84515211.09300212.18164311.729764
MSC_05.CEL9.75724410.6577659.5355789.6518088.2918818.0281797.30920110.2465899.9006885.466357...7.9475339.77897810.26366710.44401710.0253675.6128057.88633911.41706612.19605211.910514
MSC_06.CEL9.10042410.7511909.3039889.5151817.6783937.7327786.6981209.6522839.3913125.691015...6.9328109.6228809.93821510.0508379.4368776.0186257.50093511.16794311.96076111.647615
MSC_07.CEL9.73890610.9969079.6544239.8240978.1581847.7197637.46999610.7077749.9754675.649973...6.2946009.83536410.32402610.41099410.0330425.5890677.98055111.49152112.01523511.279819
MSC_08.CEL9.22596110.5512919.2389209.5750707.6542457.5713466.5406159.6894319.3767885.490835...7.0886409.46205710.1610129.8431799.3926565.7593447.69071711.13756511.70406011.342765
MSC_09.CEL9.48718110.9263129.4461859.9608667.8421277.8993717.53736410.3451919.6409045.474577...6.7414829.74353410.10116510.2444109.8158065.7225557.69471011.47606212.00390011.325244
MSC_10.CEL9.43690310.7182779.1120269.6279697.3896627.7115077.0866029.8416389.5299065.535374...6.7754699.5950669.93546110.0986489.6514035.8933257.73913411.26493811.81869811.393437
DC2.CEL8.48474710.1114748.6055928.3959127.0320197.2154498.3973628.9436858.0146965.527364...7.4426758.8211109.4458239.7684419.1952236.3713247.76101910.07184712.17810510.824970
DB1.CEL7.2809849.2978578.0985328.2923517.2385697.3977619.0618298.7675677.4556565.696851...7.1837938.8936599.3178169.1289088.8268197.8571779.2257899.63263611.2433468.256929
DC3.CEL8.2411699.5513967.8932778.6381396.8119907.3604977.7526849.1053118.5598925.865088...8.0300029.4316139.04271810.0132019.2162147.8865788.25894511.18322711.56681810.199466
DB3.CEL7.5346969.2572597.2913748.3643996.9666787.3968667.4211228.5360317.7585985.528322...7.0212428.9237778.9388788.4818787.7299317.4846968.8113919.77852710.6990398.598856
DC1.CEL8.5577859.8949088.8999758.4092247.3510347.2811028.3476778.9552187.5769055.740899...8.1844419.1451989.4649949.6325729.1565226.8410678.03198110.26342011.47650210.603380
\n", + "

545 rows × 5549 columns

\n", + "
" + ], + "text/plain": [ + " PA0001 PA0002 \\\n", + "GSM1146022_pJN105_1.CEL 9.469630 10.170614 \n", + "GSM1146023_pJN105_2.CEL 9.617634 9.539554 \n", + "GSM1146024_phaF_1.CEL 9.650212 10.489798 \n", + "GSM1146025_phaF_2.CEL 9.450308 9.921177 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 9.049257 9.927143 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 8.833167 9.917035 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 8.884647 9.907316 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 8.778351 9.872437 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 9.061243 9.828194 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 8.808541 10.165703 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 9.271641 11.114859 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 9.171547 10.747764 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 8.982648 11.029425 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 9.034591 10.786322 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 9.033705 10.742948 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 9.064427 10.832332 \n", + "Overhage11002_Pae_G1a.CEL 9.060712 10.259015 \n", + "Overhage5002_Pae_G1a.CEL 8.626041 10.367543 \n", + "Overhage11001_Pae_G1a.CEL 9.007240 10.451453 \n", + "Overhage5001_Pae_G1a.CEL 9.034428 10.133478 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 8.606120 9.802125 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 8.444531 9.619642 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 8.353272 9.706609 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 9.057750 9.750199 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 8.635089 9.530069 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 8.675308 9.665308 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 8.593110 9.894153 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 8.540164 9.996912 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 8.542963 9.905627 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 9.183519 9.930240 \n", + "... ... ... \n", + "GSM267256.CEL 8.236686 9.905366 \n", + "GSM267257.CEL 7.805926 9.577288 \n", + "GSM267258.CEL 8.388989 10.120769 \n", + "GSM267259.CEL 8.502469 10.151618 \n", + "54375-4-05.CEL 9.327996 10.781977 \n", + "dPA54375-18-05.CEL 9.428514 10.632836 \n", + "WT12935-4-05.CEL 9.266802 10.712017 \n", + "WT12935-18-05.CEL 9.204897 10.482059 \n", + "GSM234928.CEL 8.988623 10.349278 \n", + "GSM234929.CEL 7.603389 8.958421 \n", + "GSM199982.CEL 8.636051 10.064033 \n", + "GSM199983.CEL 8.491452 10.135200 \n", + "GSM199984.CEL 8.263999 10.355626 \n", + "GSM199985.CEL 8.347746 10.304444 \n", + "GSM199986.CEL 8.403669 10.477428 \n", + "MSC_01.CEL 9.808105 11.109742 \n", + "MSC_02.CEL 9.699633 10.598306 \n", + "MSC_03.CEL 9.643530 10.894112 \n", + "MSC_04.CEL 9.651675 10.793121 \n", + "MSC_05.CEL 9.757244 10.657765 \n", + "MSC_06.CEL 9.100424 10.751190 \n", + "MSC_07.CEL 9.738906 10.996907 \n", + "MSC_08.CEL 9.225961 10.551291 \n", + "MSC_09.CEL 9.487181 10.926312 \n", + "MSC_10.CEL 9.436903 10.718277 \n", + "DC2.CEL 8.484747 10.111474 \n", + "DB1.CEL 7.280984 9.297857 \n", + "DC3.CEL 8.241169 9.551396 \n", + "DB3.CEL 7.534696 9.257259 \n", + "DC1.CEL 8.557785 9.894908 \n", + "\n", + " PA0003 PA0004 \\\n", + "GSM1146022_pJN105_1.CEL 8.468516 9.585662 \n", + "GSM1146023_pJN105_2.CEL 9.922237 9.169949 \n", + "GSM1146024_phaF_1.CEL 8.520705 9.066560 \n", + "GSM1146025_phaF_2.CEL 8.465899 9.741961 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 8.885547 8.804660 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 9.009681 8.900852 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 8.737792 8.628758 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 8.755126 8.662006 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 8.342299 8.842026 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 8.627964 8.689108 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 8.552550 9.782905 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 8.658247 9.729817 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 8.521025 10.075477 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 8.842436 9.727945 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 8.699302 9.783881 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 8.606014 9.892175 \n", + "Overhage11002_Pae_G1a.CEL 8.332878 8.939922 \n", + "Overhage5002_Pae_G1a.CEL 8.440287 9.112822 \n", + "Overhage11001_Pae_G1a.CEL 8.263856 8.922851 \n", + "Overhage5001_Pae_G1a.CEL 8.153530 8.842877 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 8.196461 7.921576 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 8.516201 8.252760 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 8.187429 8.352529 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 8.499386 8.821272 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 8.309697 8.486751 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 8.236043 8.284794 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 8.233966 8.483211 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 7.960548 8.496286 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 8.446055 8.609360 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 8.351680 9.065364 \n", + "... ... ... \n", + "GSM267256.CEL 8.127148 8.554866 \n", + "GSM267257.CEL 8.171277 8.528994 \n", + "GSM267258.CEL 8.105507 8.842470 \n", + "GSM267259.CEL 7.932669 9.191258 \n", + "54375-4-05.CEL 9.169988 10.269239 \n", + "dPA54375-18-05.CEL 8.874866 9.816739 \n", + "WT12935-4-05.CEL 8.986237 10.422100 \n", + "WT12935-18-05.CEL 8.743051 9.824223 \n", + "GSM234928.CEL 8.432600 8.765975 \n", + "GSM234929.CEL 7.905264 7.808308 \n", + "GSM199982.CEL 8.380518 9.061947 \n", + "GSM199983.CEL 8.410486 9.159002 \n", + "GSM199984.CEL 8.398946 9.469057 \n", + "GSM199985.CEL 8.424055 9.234425 \n", + "GSM199986.CEL 8.347729 9.199735 \n", + "MSC_01.CEL 10.192391 9.907158 \n", + "MSC_02.CEL 9.894967 9.755481 \n", + "MSC_03.CEL 9.862115 9.850027 \n", + "MSC_04.CEL 9.723866 9.889458 \n", + "MSC_05.CEL 9.535578 9.651808 \n", + "MSC_06.CEL 9.303988 9.515181 \n", + "MSC_07.CEL 9.654423 9.824097 \n", + "MSC_08.CEL 9.238920 9.575070 \n", + "MSC_09.CEL 9.446185 9.960866 \n", + "MSC_10.CEL 9.112026 9.627969 \n", + "DC2.CEL 8.605592 8.395912 \n", + "DB1.CEL 8.098532 8.292351 \n", + "DC3.CEL 7.893277 8.638139 \n", + "DB3.CEL 7.291374 8.364399 \n", + "DC1.CEL 8.899975 8.409224 \n", + "\n", + " PA0005 PA0006 \\\n", + "GSM1146022_pJN105_1.CEL 8.353823 8.452549 \n", + "GSM1146023_pJN105_2.CEL 8.071916 9.238627 \n", + "GSM1146024_phaF_1.CEL 8.272158 8.476515 \n", + "GSM1146025_phaF_2.CEL 8.759061 8.202494 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 5.988185 7.764461 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 6.096402 7.749163 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 6.270097 7.989337 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 7.212951 8.426300 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 6.465854 7.970151 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 6.905749 8.306635 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 6.993670 7.025952 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 7.456565 7.552016 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 6.910620 6.965677 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 7.293883 7.558881 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 7.061287 7.537123 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 6.864836 7.452993 \n", + "Overhage11002_Pae_G1a.CEL 7.065205 7.184186 \n", + "Overhage5002_Pae_G1a.CEL 7.170158 7.123439 \n", + "Overhage11001_Pae_G1a.CEL 7.207694 7.135823 \n", + "Overhage5001_Pae_G1a.CEL 7.004418 7.412837 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 6.671395 7.336787 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 6.761113 7.666228 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 6.808634 7.379657 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 8.311468 8.458394 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 8.271248 8.121901 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 8.473435 7.893856 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 6.789284 7.677593 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 7.227148 7.748105 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 7.033318 7.521698 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 8.314030 8.485059 \n", + "... ... ... \n", + "GSM267256.CEL 6.958101 7.167728 \n", + "GSM267257.CEL 7.105380 7.110171 \n", + "GSM267258.CEL 6.496534 6.882491 \n", + "GSM267259.CEL 6.797057 7.040434 \n", + "54375-4-05.CEL 7.237999 7.663758 \n", + "dPA54375-18-05.CEL 7.489214 7.849677 \n", + "WT12935-4-05.CEL 7.284721 7.994735 \n", + "WT12935-18-05.CEL 7.507430 7.645802 \n", + "GSM234928.CEL 6.621127 7.166571 \n", + "GSM234929.CEL 6.769942 7.271752 \n", + "GSM199982.CEL 6.795202 6.784250 \n", + "GSM199983.CEL 6.667518 6.763448 \n", + "GSM199984.CEL 6.963805 7.263057 \n", + "GSM199985.CEL 6.836557 7.077712 \n", + "GSM199986.CEL 6.670236 7.205898 \n", + "MSC_01.CEL 8.006105 8.187194 \n", + "MSC_02.CEL 8.288743 7.961103 \n", + "MSC_03.CEL 8.130436 7.771043 \n", + "MSC_04.CEL 8.144302 7.833634 \n", + "MSC_05.CEL 8.291881 8.028179 \n", + "MSC_06.CEL 7.678393 7.732778 \n", + "MSC_07.CEL 8.158184 7.719763 \n", + "MSC_08.CEL 7.654245 7.571346 \n", + "MSC_09.CEL 7.842127 7.899371 \n", + "MSC_10.CEL 7.389662 7.711507 \n", + "DC2.CEL 7.032019 7.215449 \n", + "DB1.CEL 7.238569 7.397761 \n", + "DC3.CEL 6.811990 7.360497 \n", + "DB3.CEL 6.966678 7.396866 \n", + "DC1.CEL 7.351034 7.281102 \n", + "\n", + " PA0007 PA0008 \\\n", + "GSM1146022_pJN105_1.CEL 7.354845 9.913560 \n", + "GSM1146023_pJN105_2.CEL 7.923988 9.508516 \n", + "GSM1146024_phaF_1.CEL 6.845883 9.777121 \n", + "GSM1146025_phaF_2.CEL 7.625642 9.610623 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 8.350282 7.774165 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 8.319773 8.301315 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 8.304787 7.953646 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 8.670188 8.653405 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 8.432160 8.226710 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 8.780996 8.567739 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 8.412786 9.028318 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 8.120101 8.377144 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 7.933983 9.305858 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 7.806745 8.705449 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 7.711549 8.541648 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 7.722604 9.019312 \n", + "Overhage11002_Pae_G1a.CEL 7.038994 8.721053 \n", + "Overhage5002_Pae_G1a.CEL 7.195722 8.446453 \n", + "Overhage11001_Pae_G1a.CEL 7.328288 8.642203 \n", + "Overhage5001_Pae_G1a.CEL 6.965111 7.922488 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 8.092581 8.113993 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 8.601331 8.049111 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 8.182889 8.105783 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 7.845286 7.946517 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 8.017521 7.683863 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 7.995304 7.837666 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 7.713611 8.284396 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 7.787747 8.504486 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 7.876582 8.389326 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 7.919301 8.296146 \n", + "... ... ... \n", + "GSM267256.CEL 8.083132 8.208469 \n", + "GSM267257.CEL 7.675362 8.715254 \n", + "GSM267258.CEL 8.088547 8.342653 \n", + "GSM267259.CEL 8.001134 8.456195 \n", + "54375-4-05.CEL 6.855194 9.631573 \n", + "dPA54375-18-05.CEL 7.264132 9.526386 \n", + "WT12935-4-05.CEL 7.328312 9.596345 \n", + "WT12935-18-05.CEL 7.171655 9.749920 \n", + "GSM234928.CEL 8.195469 8.922925 \n", + "GSM234929.CEL 7.557190 8.646490 \n", + "GSM199982.CEL 8.833868 8.107349 \n", + "GSM199983.CEL 9.027041 8.417649 \n", + "GSM199984.CEL 8.928576 8.633771 \n", + "GSM199985.CEL 8.480591 8.669057 \n", + "GSM199986.CEL 8.197988 8.496536 \n", + "MSC_01.CEL 7.310598 9.900762 \n", + "MSC_02.CEL 7.311834 9.991051 \n", + "MSC_03.CEL 7.400751 10.437901 \n", + "MSC_04.CEL 7.103981 9.966521 \n", + "MSC_05.CEL 7.309201 10.246589 \n", + "MSC_06.CEL 6.698120 9.652283 \n", + "MSC_07.CEL 7.469996 10.707774 \n", + "MSC_08.CEL 6.540615 9.689431 \n", + "MSC_09.CEL 7.537364 10.345191 \n", + "MSC_10.CEL 7.086602 9.841638 \n", + "DC2.CEL 8.397362 8.943685 \n", + "DB1.CEL 9.061829 8.767567 \n", + "DC3.CEL 7.752684 9.105311 \n", + "DB3.CEL 7.421122 8.536031 \n", + "DC1.CEL 8.347677 8.955218 \n", + "\n", + " PA0009 PA0010 \\\n", + "GSM1146022_pJN105_1.CEL 8.258423 5.445693 \n", + "GSM1146023_pJN105_2.CEL 8.174457 6.206660 \n", + "GSM1146024_phaF_1.CEL 8.030193 5.532491 \n", + "GSM1146025_phaF_2.CEL 8.068657 5.538607 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 7.774105 5.510923 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 7.600733 5.706577 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 7.694889 5.679747 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 7.737566 5.695070 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 7.877492 5.785088 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 7.190508 5.742351 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 7.918787 5.318933 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 8.251262 6.064736 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 8.360502 5.381044 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 8.099493 5.903732 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 7.807424 5.775868 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 7.854875 5.668111 \n", + "Overhage11002_Pae_G1a.CEL 8.357072 5.635459 \n", + "Overhage5002_Pae_G1a.CEL 8.380196 5.632470 \n", + "Overhage11001_Pae_G1a.CEL 8.361854 5.674192 \n", + "Overhage5001_Pae_G1a.CEL 8.246581 6.276085 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 7.845790 5.535163 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 7.756101 5.414321 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 7.884737 5.563755 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 7.744025 5.238127 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 7.918544 5.343945 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 7.562524 5.325558 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 7.607364 5.669414 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 7.613045 5.490780 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 7.672961 5.450242 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 8.192719 5.556262 \n", + "... ... ... \n", + "GSM267256.CEL 7.639126 5.580815 \n", + "GSM267257.CEL 7.598091 5.470109 \n", + "GSM267258.CEL 7.821589 5.506512 \n", + "GSM267259.CEL 8.069983 5.492802 \n", + "54375-4-05.CEL 9.404465 5.684067 \n", + "dPA54375-18-05.CEL 9.535493 5.708800 \n", + "WT12935-4-05.CEL 9.373494 5.720567 \n", + "WT12935-18-05.CEL 9.468067 5.660903 \n", + "GSM234928.CEL 8.438846 5.363427 \n", + "GSM234929.CEL 7.824607 5.623979 \n", + "GSM199982.CEL 8.027142 5.205947 \n", + "GSM199983.CEL 8.076362 5.140327 \n", + "GSM199984.CEL 8.045749 5.154168 \n", + "GSM199985.CEL 7.930413 5.375658 \n", + "GSM199986.CEL 8.170460 5.307389 \n", + "MSC_01.CEL 10.121996 5.474449 \n", + "MSC_02.CEL 9.756418 5.468767 \n", + "MSC_03.CEL 9.913065 5.581816 \n", + "MSC_04.CEL 9.780387 5.466294 \n", + "MSC_05.CEL 9.900688 5.466357 \n", + "MSC_06.CEL 9.391312 5.691015 \n", + "MSC_07.CEL 9.975467 5.649973 \n", + "MSC_08.CEL 9.376788 5.490835 \n", + "MSC_09.CEL 9.640904 5.474577 \n", + "MSC_10.CEL 9.529906 5.535374 \n", + "DC2.CEL 8.014696 5.527364 \n", + "DB1.CEL 7.455656 5.696851 \n", + "DC3.CEL 8.559892 5.865088 \n", + "DB3.CEL 7.758598 5.528322 \n", + "DC1.CEL 7.576905 5.740899 \n", + "\n", + " ... PA5561 \\\n", + "GSM1146022_pJN105_1.CEL ... 8.790537 \n", + "GSM1146023_pJN105_2.CEL ... 7.957668 \n", + "GSM1146024_phaF_1.CEL ... 8.872988 \n", + "GSM1146025_phaF_2.CEL ... 8.763209 \n", + "GSM1244967_PAO1-22-replicate-01.CEL ... 9.356331 \n", + "GSM1244968_PAO1-22-replicate-02.CEL ... 9.486076 \n", + "GSM1244969_PAO1-22-replicate-03.CEL ... 9.080317 \n", + "GSM1244970_PAO1-37-replicate-01.CEL ... 9.153401 \n", + "GSM1244971_PAO1-37-replicate-02.CEL ... 9.337408 \n", + "GSM1244972_PAO1-37-replicate-03.CEL ... 9.013357 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... ... 6.221370 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... ... 6.224990 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... ... 6.502323 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... ... 6.725395 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... ... 6.206460 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... ... 6.382724 \n", + "Overhage11002_Pae_G1a.CEL ... 8.101930 \n", + "Overhage5002_Pae_G1a.CEL ... 7.870886 \n", + "Overhage11001_Pae_G1a.CEL ... 7.676497 \n", + "Overhage5001_Pae_G1a.CEL ... 8.236282 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL ... 8.203718 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL ... 8.151266 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL ... 7.750733 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL ... 8.037624 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL ... 8.755284 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL ... 8.353907 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL ... 7.944481 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL ... 7.506598 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL ... 7.567019 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL ... 8.742938 \n", + "... ... ... \n", + "GSM267256.CEL ... 6.690864 \n", + "GSM267257.CEL ... 6.729888 \n", + "GSM267258.CEL ... 6.823688 \n", + "GSM267259.CEL ... 6.722847 \n", + "54375-4-05.CEL ... 7.127736 \n", + "dPA54375-18-05.CEL ... 7.295711 \n", + "WT12935-4-05.CEL ... 6.968191 \n", + "WT12935-18-05.CEL ... 6.716768 \n", + "GSM234928.CEL ... 7.545325 \n", + "GSM234929.CEL ... 6.659095 \n", + "GSM199982.CEL ... 6.014054 \n", + "GSM199983.CEL ... 6.317830 \n", + "GSM199984.CEL ... 6.132991 \n", + "GSM199985.CEL ... 6.487283 \n", + "GSM199986.CEL ... 5.967711 \n", + "MSC_01.CEL ... 8.421733 \n", + "MSC_02.CEL ... 7.920496 \n", + "MSC_03.CEL ... 7.181129 \n", + "MSC_04.CEL ... 7.507405 \n", + "MSC_05.CEL ... 7.947533 \n", + "MSC_06.CEL ... 6.932810 \n", + "MSC_07.CEL ... 6.294600 \n", + "MSC_08.CEL ... 7.088640 \n", + "MSC_09.CEL ... 6.741482 \n", + "MSC_10.CEL ... 6.775469 \n", + "DC2.CEL ... 7.442675 \n", + "DB1.CEL ... 7.183793 \n", + "DC3.CEL ... 8.030002 \n", + "DB3.CEL ... 7.021242 \n", + "DC1.CEL ... 8.184441 \n", + "\n", + " PA5562 PA5563 \\\n", + "GSM1146022_pJN105_1.CEL 9.835683 9.652631 \n", + "GSM1146023_pJN105_2.CEL 10.390467 9.521621 \n", + "GSM1146024_phaF_1.CEL 9.832781 9.712714 \n", + "GSM1146025_phaF_2.CEL 9.710935 10.013331 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 7.377822 9.644671 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 6.894396 9.723022 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 7.296979 9.655950 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 7.927784 9.572730 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 8.013215 9.553362 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 7.840225 9.405921 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 9.041328 8.988923 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 8.795572 8.914357 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 9.045391 8.737919 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 9.129716 9.200521 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 9.137383 9.127785 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 9.247774 8.835899 \n", + "Overhage11002_Pae_G1a.CEL 9.115285 9.700031 \n", + "Overhage5002_Pae_G1a.CEL 8.743070 9.638768 \n", + "Overhage11001_Pae_G1a.CEL 8.756506 9.412606 \n", + "Overhage5001_Pae_G1a.CEL 8.528201 9.473295 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 8.802866 9.153777 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 8.763260 8.933147 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 8.740794 9.017917 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 8.458080 8.961175 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 8.459798 8.783803 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 8.493169 8.851353 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 8.830444 9.105121 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 8.838546 9.009189 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 8.836820 8.926911 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 8.590489 9.259179 \n", + "... ... ... \n", + "GSM267256.CEL 8.813783 8.797494 \n", + "GSM267257.CEL 8.812275 8.429931 \n", + "GSM267258.CEL 8.763580 8.630832 \n", + "GSM267259.CEL 8.651057 9.076140 \n", + "54375-4-05.CEL 9.687607 10.199612 \n", + "dPA54375-18-05.CEL 9.977159 10.130314 \n", + "WT12935-4-05.CEL 9.761209 10.118223 \n", + "WT12935-18-05.CEL 9.880321 10.341149 \n", + "GSM234928.CEL 8.849244 9.063613 \n", + "GSM234929.CEL 8.624760 8.560243 \n", + "GSM199982.CEL 8.899033 8.744948 \n", + "GSM199983.CEL 8.527190 8.705585 \n", + "GSM199984.CEL 8.327817 8.499879 \n", + "GSM199985.CEL 8.663676 8.679060 \n", + "GSM199986.CEL 8.590509 8.730627 \n", + "MSC_01.CEL 9.934451 10.339268 \n", + "MSC_02.CEL 9.753023 10.303848 \n", + "MSC_03.CEL 9.924768 10.682343 \n", + "MSC_04.CEL 9.787841 10.045511 \n", + "MSC_05.CEL 9.778978 10.263667 \n", + "MSC_06.CEL 9.622880 9.938215 \n", + "MSC_07.CEL 9.835364 10.324026 \n", + "MSC_08.CEL 9.462057 10.161012 \n", + "MSC_09.CEL 9.743534 10.101165 \n", + "MSC_10.CEL 9.595066 9.935461 \n", + "DC2.CEL 8.821110 9.445823 \n", + "DB1.CEL 8.893659 9.317816 \n", + "DC3.CEL 9.431613 9.042718 \n", + "DB3.CEL 8.923777 8.938878 \n", + "DC1.CEL 9.145198 9.464994 \n", + "\n", + " PA5564 PA5565 \\\n", + "GSM1146022_pJN105_1.CEL 9.887377 9.919375 \n", + "GSM1146023_pJN105_2.CEL 10.292927 9.616351 \n", + "GSM1146024_phaF_1.CEL 10.327820 10.401750 \n", + "GSM1146025_phaF_2.CEL 10.407397 9.906222 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 7.429156 7.654936 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 7.788555 7.605215 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 7.345836 7.659305 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 8.284933 8.580799 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 8.590636 8.628973 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 8.208101 8.480249 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 8.742518 8.558420 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 8.124617 8.261041 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 8.792514 8.769101 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 8.475397 8.441687 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 8.626448 8.150120 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 8.842497 8.507105 \n", + "Overhage11002_Pae_G1a.CEL 8.435165 8.563872 \n", + "Overhage5002_Pae_G1a.CEL 8.450761 8.604290 \n", + "Overhage11001_Pae_G1a.CEL 8.280651 8.714353 \n", + "Overhage5001_Pae_G1a.CEL 8.153423 8.564107 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 8.503778 8.716392 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 8.437675 8.313180 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 8.540282 8.784815 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 9.220858 9.441521 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 9.058716 9.350270 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 9.114260 9.433696 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 8.851829 8.666996 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 8.935717 8.750314 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 8.934700 8.734047 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 9.784402 9.890294 \n", + "... ... ... \n", + "GSM267256.CEL 8.120453 8.486073 \n", + "GSM267257.CEL 8.452266 8.591313 \n", + "GSM267258.CEL 8.301705 8.414636 \n", + "GSM267259.CEL 8.269793 8.762185 \n", + "54375-4-05.CEL 9.457152 9.318372 \n", + "dPA54375-18-05.CEL 9.372320 9.392664 \n", + "WT12935-4-05.CEL 9.692480 9.026063 \n", + "WT12935-18-05.CEL 9.762406 9.236656 \n", + "GSM234928.CEL 8.746016 8.580539 \n", + "GSM234929.CEL 8.662693 8.427061 \n", + "GSM199982.CEL 8.041866 8.429772 \n", + "GSM199983.CEL 8.078922 8.301734 \n", + "GSM199984.CEL 8.236025 8.139740 \n", + "GSM199985.CEL 8.130365 8.423268 \n", + "GSM199986.CEL 8.246411 8.196166 \n", + "MSC_01.CEL 10.395386 10.417538 \n", + "MSC_02.CEL 10.427505 10.152129 \n", + "MSC_03.CEL 10.742716 10.179796 \n", + "MSC_04.CEL 10.335545 9.837840 \n", + "MSC_05.CEL 10.444017 10.025367 \n", + "MSC_06.CEL 10.050837 9.436877 \n", + "MSC_07.CEL 10.410994 10.033042 \n", + "MSC_08.CEL 9.843179 9.392656 \n", + "MSC_09.CEL 10.244410 9.815806 \n", + "MSC_10.CEL 10.098648 9.651403 \n", + "DC2.CEL 9.768441 9.195223 \n", + "DB1.CEL 9.128908 8.826819 \n", + "DC3.CEL 10.013201 9.216214 \n", + "DB3.CEL 8.481878 7.729931 \n", + "DC1.CEL 9.632572 9.156522 \n", + "\n", + " PA5566 PA5567 \\\n", + "GSM1146022_pJN105_1.CEL 6.368828 8.233680 \n", + "GSM1146023_pJN105_2.CEL 6.818172 7.236897 \n", + "GSM1146024_phaF_1.CEL 6.825256 8.157127 \n", + "GSM1146025_phaF_2.CEL 6.502036 7.509643 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 6.131965 6.241217 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 6.231041 6.303251 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 5.702764 6.390429 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 5.959742 6.265907 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 5.778791 6.830793 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 6.232756 5.991988 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 5.919584 6.972050 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 5.637527 7.071145 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 5.682087 6.944926 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 5.357008 7.173180 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 5.710450 7.122626 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 5.550315 7.140890 \n", + "Overhage11002_Pae_G1a.CEL 5.500747 7.072423 \n", + "Overhage5002_Pae_G1a.CEL 5.231323 6.974158 \n", + "Overhage11001_Pae_G1a.CEL 5.511498 7.059334 \n", + "Overhage5001_Pae_G1a.CEL 5.656281 6.966264 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 5.959662 7.003427 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 5.867124 6.968797 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 5.898904 6.997114 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 5.848712 7.467731 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 5.748415 7.264732 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 5.935260 7.512951 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 5.812796 7.018061 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 5.791707 6.817943 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 5.819090 7.098123 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 5.599692 7.861679 \n", + "... ... ... \n", + "GSM267256.CEL 7.133500 7.235946 \n", + "GSM267257.CEL 7.267037 7.332662 \n", + "GSM267258.CEL 6.122716 7.372282 \n", + "GSM267259.CEL 6.790617 7.470121 \n", + "54375-4-05.CEL 5.523898 7.911031 \n", + "dPA54375-18-05.CEL 5.650118 7.854258 \n", + "WT12935-4-05.CEL 5.868279 7.715245 \n", + "WT12935-18-05.CEL 5.780208 7.765672 \n", + "GSM234928.CEL 6.398333 7.906096 \n", + "GSM234929.CEL 7.722039 8.614729 \n", + "GSM199982.CEL 5.831018 7.087497 \n", + "GSM199983.CEL 5.857462 6.650517 \n", + "GSM199984.CEL 6.523433 6.925561 \n", + "GSM199985.CEL 6.111759 7.011567 \n", + "GSM199986.CEL 6.124699 6.833999 \n", + "MSC_01.CEL 5.587394 8.363628 \n", + "MSC_02.CEL 5.689294 7.919645 \n", + "MSC_03.CEL 5.901795 8.023011 \n", + "MSC_04.CEL 5.584816 7.845152 \n", + "MSC_05.CEL 5.612805 7.886339 \n", + "MSC_06.CEL 6.018625 7.500935 \n", + "MSC_07.CEL 5.589067 7.980551 \n", + "MSC_08.CEL 5.759344 7.690717 \n", + "MSC_09.CEL 5.722555 7.694710 \n", + "MSC_10.CEL 5.893325 7.739134 \n", + "DC2.CEL 6.371324 7.761019 \n", + "DB1.CEL 7.857177 9.225789 \n", + "DC3.CEL 7.886578 8.258945 \n", + "DB3.CEL 7.484696 8.811391 \n", + "DC1.CEL 6.841067 8.031981 \n", + "\n", + " PA5568 PA5569 \\\n", + "GSM1146022_pJN105_1.CEL 11.346424 12.364579 \n", + "GSM1146023_pJN105_2.CEL 11.269168 11.292843 \n", + "GSM1146024_phaF_1.CEL 11.204328 12.356186 \n", + "GSM1146025_phaF_2.CEL 11.234006 12.497402 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 7.684121 9.072845 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 7.815412 8.896422 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 7.863996 9.196426 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 7.824123 10.907826 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 8.052581 10.929728 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 7.848818 10.879207 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 9.093678 10.611149 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 9.107483 10.949905 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 10.149439 11.310280 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 9.412461 11.130204 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 9.205678 11.070619 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 9.835352 11.129384 \n", + "Overhage11002_Pae_G1a.CEL 8.855315 11.039089 \n", + "Overhage5002_Pae_G1a.CEL 8.808047 10.950833 \n", + "Overhage11001_Pae_G1a.CEL 8.429056 11.180871 \n", + "Overhage5001_Pae_G1a.CEL 8.380003 11.019234 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 8.485458 10.926675 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 8.442862 10.758235 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 8.855438 10.918044 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 8.530881 10.590746 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 8.525510 10.717669 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 8.303097 10.689117 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 8.777422 10.943413 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 8.474524 10.890147 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 8.788149 11.246913 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 9.020793 11.341095 \n", + "... ... ... \n", + "GSM267256.CEL 9.521172 9.960750 \n", + "GSM267257.CEL 10.009287 10.139308 \n", + "GSM267258.CEL 9.393565 10.425283 \n", + "GSM267259.CEL 9.308889 10.366315 \n", + "54375-4-05.CEL 10.828271 11.597643 \n", + "dPA54375-18-05.CEL 11.035390 11.267679 \n", + "WT12935-4-05.CEL 10.949194 11.271363 \n", + "WT12935-18-05.CEL 11.277846 11.352950 \n", + "GSM234928.CEL 9.771389 10.747401 \n", + "GSM234929.CEL 10.121108 10.166560 \n", + "GSM199982.CEL 9.160298 10.233729 \n", + "GSM199983.CEL 8.992757 10.281689 \n", + "GSM199984.CEL 9.281547 10.420944 \n", + "GSM199985.CEL 9.448470 10.538009 \n", + "GSM199986.CEL 9.145378 10.372600 \n", + "MSC_01.CEL 11.087879 12.213009 \n", + "MSC_02.CEL 11.232582 12.361471 \n", + "MSC_03.CEL 11.504344 12.246109 \n", + "MSC_04.CEL 11.093002 12.181643 \n", + "MSC_05.CEL 11.417066 12.196052 \n", + "MSC_06.CEL 11.167943 11.960761 \n", + "MSC_07.CEL 11.491521 12.015235 \n", + "MSC_08.CEL 11.137565 11.704060 \n", + "MSC_09.CEL 11.476062 12.003900 \n", + "MSC_10.CEL 11.264938 11.818698 \n", + "DC2.CEL 10.071847 12.178105 \n", + "DB1.CEL 9.632636 11.243346 \n", + "DC3.CEL 11.183227 11.566818 \n", + "DB3.CEL 9.778527 10.699039 \n", + "DC1.CEL 10.263420 11.476502 \n", + "\n", + " PA5570 \n", + "GSM1146022_pJN105_1.CEL 12.116378 \n", + "GSM1146023_pJN105_2.CEL 10.810757 \n", + "GSM1146024_phaF_1.CEL 11.888967 \n", + "GSM1146025_phaF_2.CEL 12.137581 \n", + "GSM1244967_PAO1-22-replicate-01.CEL 10.695175 \n", + "GSM1244968_PAO1-22-replicate-02.CEL 10.714222 \n", + "GSM1244969_PAO1-22-replicate-03.CEL 10.671757 \n", + "GSM1244970_PAO1-37-replicate-01.CEL 12.177075 \n", + "GSM1244971_PAO1-37-replicate-02.CEL 12.152272 \n", + "GSM1244972_PAO1-37-replicate-03.CEL 12.175344 \n", + "GSM1237734_M9_H103_2_51059600653056031211409890... 9.728216 \n", + "GSM1237735_M9_H103_3_51059600653061050411410396... 10.030924 \n", + "GSM1237736_M9_H103_4_51059600653061050411410396... 10.723607 \n", + "GSM1237737_M9_PAOSX_1_5105960065306005041141039... 10.392338 \n", + "GSM1237738_M9_PAOSX_3_5105960065306005041141039... 10.266992 \n", + "GSM1237739_M9_PAOSX_4_5105960065306105041141039... 10.490768 \n", + "Overhage11002_Pae_G1a.CEL 10.343857 \n", + "Overhage5002_Pae_G1a.CEL 10.236251 \n", + "Overhage11001_Pae_G1a.CEL 10.486374 \n", + "Overhage5001_Pae_G1a.CEL 10.340256 \n", + "GSM838206_OXYR-LB-1_Pae_G1a.CEL 10.660376 \n", + "GSM838207_OXYR-LB-2_Pae_G1a.CEL 10.065086 \n", + "GSM838208_OXYR-LB-4_Pae_G1a.CEL 10.539477 \n", + "GSM838209_OXYR-PM-1_Pae_G1a.CEL 10.163238 \n", + "GSM838210_OXYR-PM-3_Pae_G1a.CEL 10.294786 \n", + "GSM838211_OXYR-PM-4_Pae_G1a.CEL 10.221476 \n", + "GSM838212_PAO1-LB-1_Pae_G1a.CEL 11.017426 \n", + "GSM838213_PAO1-LB-2_Pae_G1a.CEL 10.733528 \n", + "GSM838214_PAO1-LB-3_Pae_G1a.CEL 11.015347 \n", + "GSM838215_PAO1-PM-1_Pae_G1a.CEL 10.742094 \n", + "... ... \n", + "GSM267256.CEL 8.022413 \n", + "GSM267257.CEL 7.958096 \n", + "GSM267258.CEL 9.132786 \n", + "GSM267259.CEL 8.997943 \n", + "54375-4-05.CEL 11.268520 \n", + "dPA54375-18-05.CEL 10.867690 \n", + "WT12935-4-05.CEL 10.732218 \n", + "WT12935-18-05.CEL 10.970310 \n", + "GSM234928.CEL 8.877742 \n", + "GSM234929.CEL 6.876660 \n", + "GSM199982.CEL 8.417952 \n", + "GSM199983.CEL 8.721675 \n", + "GSM199984.CEL 8.622205 \n", + "GSM199985.CEL 8.674091 \n", + "GSM199986.CEL 8.760325 \n", + "MSC_01.CEL 11.736927 \n", + "MSC_02.CEL 11.974702 \n", + "MSC_03.CEL 11.354957 \n", + "MSC_04.CEL 11.729764 \n", + "MSC_05.CEL 11.910514 \n", + "MSC_06.CEL 11.647615 \n", + "MSC_07.CEL 11.279819 \n", + "MSC_08.CEL 11.342765 \n", + "MSC_09.CEL 11.325244 \n", + "MSC_10.CEL 11.393437 \n", + "DC2.CEL 10.824970 \n", + "DB1.CEL 8.256929 \n", + "DC3.CEL 10.199466 \n", + "DB3.CEL 8.598856 \n", + "DC1.CEL 10.603380 \n", + "\n", + "[545 rows x 5549 columns]" + ] + }, + "execution_count": 8, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Drop samples with no expression activity associated\n", + "pao1_raw_compendium.dropna(inplace=True)\n", + "\n", + "print(pao1_raw_compendium.shape)\n", + "pao1_raw_compendium" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "metadata": {}, + "outputs": [], + "source": [ + "# Check samples associated with project_id are still in subset\n", + "project_sample_ids = list(project_sample_ids[\"Sample\"])\n", + "\n", + "for sample_id in project_sample_ids:\n", + " assert sample_id in list(pao1_raw_compendium.index)" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "metadata": {}, + "outputs": [], + "source": [ + "# Save filtered compendium\n", + "pao1_raw_compendium.T.to_csv(out_compendium_filename, sep=\"\\t\")" + ] + } + ], + "metadata": { + "finalized": { + "timestamp": 1592246126078, + "trusted": true + }, + "kernelspec": { + "display_name": "Python [conda env:generic_expression] *", + "language": "python", + "name": "conda-env-generic_expression-py" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.7.9" + } + }, + "nbformat": 4, + "nbformat_minor": 4 +} diff --git a/pseudomonas_analysis/1_process_pseudomonas_data.ipynb b/pseudomonas_analysis/1_process_pseudomonas_data.ipynb index fe3d38c2..6e837c4e 100644 --- a/pseudomonas_analysis/1_process_pseudomonas_data.ipynb +++ b/pseudomonas_analysis/1_process_pseudomonas_data.ipynb @@ -19,22 +19,22 @@ "scrolled": false }, "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/ponyo/helper_vae.py:21: The name tf.ConfigProto is deprecated. Please use tf.compat.v1.ConfigProto instead.\n", + "\n", + "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/ponyo/helper_vae.py:25: The name tf.Session is deprecated. Please use tf.compat.v1.Session instead.\n", + "\n", + "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/ponyo/helper_vae.py:25: The name tf.get_default_graph is deprecated. Please use tf.compat.v1.get_default_graph instead.\n", + "\n" + ] + }, { "name": "stderr", "output_type": "stream", "text": [ - "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/framework/dtypes.py:526: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy, it will be understood as (type, (1,)) / '(1,)type'.\n", - " _np_qint8 = np.dtype([(\"qint8\", np.int8, 1)])\n", - "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/framework/dtypes.py:527: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy, it will be understood as (type, (1,)) / '(1,)type'.\n", - " _np_quint8 = np.dtype([(\"quint8\", np.uint8, 1)])\n", - "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/framework/dtypes.py:528: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy, it will be understood as (type, (1,)) / '(1,)type'.\n", - " _np_qint16 = np.dtype([(\"qint16\", np.int16, 1)])\n", - "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/framework/dtypes.py:529: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy, it will be understood as (type, (1,)) / '(1,)type'.\n", - " _np_quint16 = np.dtype([(\"quint16\", np.uint16, 1)])\n", - "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/framework/dtypes.py:530: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy, it will be understood as (type, (1,)) / '(1,)type'.\n", - " _np_qint32 = np.dtype([(\"qint32\", np.int32, 1)])\n", - "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/framework/dtypes.py:535: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy, it will be understood as (type, (1,)) / '(1,)type'.\n", - " np_resource = np.dtype([(\"resource\", np.ubyte, 1)])\n", "Using TensorFlow backend.\n", "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/matplotlib/__init__.py:886: MatplotlibDeprecationWarning: \n", "examples.directory is deprecated; in the future, examples will be found relative to the 'datapath' directory.\n", @@ -59,9 +59,18 @@ }, { "cell_type": "code", - "execution_count": null, + "execution_count": 2, "metadata": {}, - "outputs": [], + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "WARNING:tensorflow:From /home/alexandra/Documents/Repos/generic-expression-patterns/generic_expression_patterns_modules/process.py:57: The name tf.set_random_seed is deprecated. Please use tf.compat.v1.set_random_seed instead.\n", + "\n" + ] + } + ], "source": [ "# Set seeds to get reproducible VAE trained models\n", "process.set_all_seeds()" @@ -78,7 +87,7 @@ }, { "cell_type": "code", - "execution_count": 2, + "execution_count": 3, "metadata": {}, "outputs": [], "source": [ @@ -86,7 +95,7 @@ "\n", "# Read in config variables\n", "config_filename = os.path.abspath(\n", - " os.path.join(base_dir, \"configs\", \"config_pseudomonas_33245.tsv\")\n", + " os.path.join(base_dir, \"configs\", \"config_pseudomonas_pao1.tsv\")\n", ")\n", "\n", "params = utils.read_config(config_filename)\n", @@ -135,7 +144,7 @@ }, { "cell_type": "code", - "execution_count": 3, + "execution_count": 4, "metadata": {}, "outputs": [], "source": [ @@ -147,6 +156,28 @@ ")" ] }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## Get raw pseudomonas template experiment" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "metadata": {}, + "outputs": [], + "source": [ + "process.process_raw_template_pseudomonas(\n", + " processed_compendium_filename,\n", + " project_id,\n", + " dataset_name,\n", + " metadata_colname,\n", + " raw_template_filename,\n", + ")" + ] + }, { "cell_type": "markdown", "metadata": {}, @@ -169,7 +200,7 @@ }, { "cell_type": "code", - "execution_count": 6, + "execution_count": 5, "metadata": {}, "outputs": [], "source": [ @@ -189,7 +220,7 @@ }, { "cell_type": "code", - "execution_count": 7, + "execution_count": 6, "metadata": { "scrolled": true }, @@ -198,14 +229,14 @@ "name": "stdout", "output_type": "stream", "text": [ - "input dataset contains 950 samples and 5549 genes\n", - "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/ops/resource_variable_ops.py:435: colocate_with (from tensorflow.python.framework.ops) is deprecated and will be removed in a future version.\n", + "input dataset contains 545 samples and 5549 genes\n", + "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow_core/python/ops/resource_variable_ops.py:1630: calling BaseResourceVariable.__init__ (from tensorflow.python.ops.resource_variable_ops) with constraint is deprecated and will be removed in a future version.\n", "Instructions for updating:\n", - "Colocations handled automatically by placer.\n", + "If using Keras pass *_constraint arguments to layers.\n", "tracking beta\n", - "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow/python/ops/math_ops.py:3066: to_int32 (from tensorflow.python.ops.math_ops) is deprecated and will be removed in a future version.\n", + "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow_core/python/ops/nn_impl.py:183: where (from tensorflow.python.ops.array_ops) is deprecated and will be removed in a future version.\n", "Instructions for updating:\n", - "Use tf.cast instead.\n" + "Use tf.where in 2.0, which has the same broadcast rule as np.where\n" ] }, { @@ -220,212 +251,220 @@ "name": "stdout", "output_type": "stream", "text": [ - "Train on 712 samples, validate on 238 samples\n", + "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/keras/backend/tensorflow_backend.py:422: The name tf.global_variables is deprecated. Please use tf.compat.v1.global_variables instead.\n", + "\n", + "Train on 409 samples, validate on 136 samples\n", "Epoch 1/100\n", - "712/712 [==============================] - 31s 44ms/step - loss: 3519.7467 - val_loss: 3718.3970\n", + "409/409 [==============================] - 20s 50ms/step - loss: 3551.1328 - val_loss: 3953.5014\n", "Epoch 2/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3477.0322 - val_loss: 3538.8910\n", + "409/409 [==============================] - 19s 48ms/step - loss: 3494.5552 - val_loss: 3548.4125\n", "Epoch 3/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3465.8347 - val_loss: 3450.7159\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3484.6187 - val_loss: 3493.9662\n", "Epoch 4/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3453.2178 - val_loss: 3436.2781\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3484.2529 - val_loss: 3466.8443\n", "Epoch 5/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3448.2561 - val_loss: 3430.3111\n", + "409/409 [==============================] - 19s 48ms/step - loss: 3472.1516 - val_loss: 3442.4145\n", "Epoch 6/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3436.3102 - val_loss: 3424.3456\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3464.5701 - val_loss: 3445.8328\n", "Epoch 7/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3433.0736 - val_loss: 3411.4579\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3453.8515 - val_loss: 3421.4832\n", "Epoch 8/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3425.5651 - val_loss: 3414.5145\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3451.3738 - val_loss: 3424.9723\n", "Epoch 9/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3418.2921 - val_loss: 3408.6735\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3440.1852 - val_loss: 3411.0756\n", "Epoch 10/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3416.1393 - val_loss: 3398.3858\n", + "409/409 [==============================] - 19s 48ms/step - loss: 3441.0338 - val_loss: 3407.9352\n", "Epoch 11/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3408.4615 - val_loss: 3402.4462\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3429.1260 - val_loss: 3412.8633\n", "Epoch 12/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3408.2405 - val_loss: 3391.6314\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3431.3071 - val_loss: 3420.1285\n", "Epoch 13/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3405.1307 - val_loss: 3388.4294\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3426.9214 - val_loss: 3394.6676\n", "Epoch 14/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3395.5802 - val_loss: 3384.3428\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3423.1694 - val_loss: 3391.2636\n", "Epoch 15/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3390.6724 - val_loss: 3384.4866\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3415.0683 - val_loss: 3388.0017\n", "Epoch 16/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3388.1861 - val_loss: 3379.7482\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3408.0997 - val_loss: 3392.9762\n", "Epoch 17/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3386.5533 - val_loss: 3370.4699\n", + "409/409 [==============================] - 19s 48ms/step - loss: 3400.4317 - val_loss: 3386.3258\n", "Epoch 18/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3382.9619 - val_loss: 3375.7588\n", + "409/409 [==============================] - 20s 49ms/step - loss: 3400.6260 - val_loss: 3379.8830\n", "Epoch 19/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3378.2592 - val_loss: 3375.4652\n", + "409/409 [==============================] - 21s 50ms/step - loss: 3397.2155 - val_loss: 3394.5263\n", "Epoch 20/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3375.3465 - val_loss: 3373.0691\n", + "409/409 [==============================] - 20s 48ms/step - loss: 3394.3337 - val_loss: 3382.3562\n", "Epoch 21/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3371.9678 - val_loss: 3370.3357\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3383.6010 - val_loss: 3378.7313\n", "Epoch 22/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3367.7974 - val_loss: 3361.5928\n", + "409/409 [==============================] - 19s 48ms/step - loss: 3388.4148 - val_loss: 3379.3993\n", "Epoch 23/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3368.6075 - val_loss: 3362.1716\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3382.9890 - val_loss: 3367.4554\n", "Epoch 24/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3364.7191 - val_loss: 3363.5416\n", + "409/409 [==============================] - 20s 49ms/step - loss: 3375.2968 - val_loss: 3371.1287\n", "Epoch 25/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3359.5673 - val_loss: 3359.6562\n", + "409/409 [==============================] - 21s 51ms/step - loss: 3375.8513 - val_loss: 3366.9889\n", "Epoch 26/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3360.3120 - val_loss: 3358.9760\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3370.6594 - val_loss: 3354.0594\n", "Epoch 27/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3356.9393 - val_loss: 3356.8812\n", + "409/409 [==============================] - 20s 48ms/step - loss: 3365.9916 - val_loss: 3354.7996\n", "Epoch 28/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3356.7878 - val_loss: 3352.2668\n", + "409/409 [==============================] - 20s 48ms/step - loss: 3366.9813 - val_loss: 3351.8500\n", "Epoch 29/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3351.4480 - val_loss: 3351.1642\n", + "409/409 [==============================] - 20s 49ms/step - loss: 3369.4684 - val_loss: 3352.5050\n", "Epoch 30/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3352.1451 - val_loss: 3349.3642\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3364.9416 - val_loss: 3354.8823\n", "Epoch 31/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3345.2871 - val_loss: 3349.1423\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3353.4722 - val_loss: 3348.4784\n", "Epoch 32/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3347.9343 - val_loss: 3345.6125\n", + "409/409 [==============================] - 20s 48ms/step - loss: 3354.2557 - val_loss: 3349.1507\n", "Epoch 33/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3344.0632 - val_loss: 3348.2038\n", + "409/409 [==============================] - 21s 50ms/step - loss: 3360.3163 - val_loss: 3342.0245\n", "Epoch 34/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3341.9178 - val_loss: 3342.3568\n", + "409/409 [==============================] - 20s 49ms/step - loss: 3355.5817 - val_loss: 3346.1323\n", "Epoch 35/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3337.7741 - val_loss: 3339.9798\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3349.7000 - val_loss: 3342.3681\n", "Epoch 36/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3336.2090 - val_loss: 3336.0879\n", + "409/409 [==============================] - 20s 48ms/step - loss: 3345.2161 - val_loss: 3351.1421\n", "Epoch 37/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3337.0502 - val_loss: 3336.8827\n", + "409/409 [==============================] - 20s 49ms/step - loss: 3344.7997 - val_loss: 3337.9300\n", "Epoch 38/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3331.3839 - val_loss: 3338.2964\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3333.3311 - val_loss: 3335.8842\n", "Epoch 39/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3330.6805 - val_loss: 3332.7585\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3339.0509 - val_loss: 3340.2661\n", "Epoch 40/100\n", - "712/712 [==============================] - 31s 43ms/step - loss: 3332.8183 - val_loss: 3334.1698\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3338.7016 - val_loss: 3346.5607\n", "Epoch 41/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3325.2412 - val_loss: 3334.4169\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3335.0119 - val_loss: 3339.6119\n", "Epoch 42/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3324.3044 - val_loss: 3331.9216\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3336.1556 - val_loss: 3330.0425\n", "Epoch 43/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3323.6137 - val_loss: 3331.1343\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3338.5539 - val_loss: 3335.3698\n", "Epoch 44/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3322.2121 - val_loss: 3329.8849\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3330.8419 - val_loss: 3330.3555\n", "Epoch 45/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3320.1922 - val_loss: 3328.1651\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3333.1842 - val_loss: 3327.7860\n", "Epoch 46/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3316.7572 - val_loss: 3326.3525\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3325.4235 - val_loss: 3323.6540\n", "Epoch 47/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3319.2455 - val_loss: 3326.0255\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3329.8973 - val_loss: 3326.3185\n", "Epoch 48/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3318.7793 - val_loss: 3326.7939\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3326.6162 - val_loss: 3323.2829\n", "Epoch 49/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3316.3430 - val_loss: 3325.6276\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3325.2623 - val_loss: 3325.1811\n", "Epoch 50/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3313.7546 - val_loss: 3322.6603\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3322.6340 - val_loss: 3332.9074\n", "Epoch 51/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3312.2715 - val_loss: 3323.5773\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3319.7635 - val_loss: 3322.1188\n", "Epoch 52/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3317.0800 - val_loss: 3323.6604\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3319.9238 - val_loss: 3316.6392\n", "Epoch 53/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3310.9724 - val_loss: 3318.5197\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3321.0498 - val_loss: 3320.8643\n", "Epoch 54/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3307.5385 - val_loss: 3319.8629\n", + "409/409 [==============================] - 20s 48ms/step - loss: 3317.3719 - val_loss: 3321.3111\n", "Epoch 55/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3306.8801 - val_loss: 3321.8960\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3315.1467 - val_loss: 3318.8556\n", "Epoch 56/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3307.3237 - val_loss: 3319.0809\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3315.3976 - val_loss: 3315.7092\n", "Epoch 57/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3305.2526 - val_loss: 3318.5680\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3308.1340 - val_loss: 3309.1480\n", "Epoch 58/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3302.8005 - val_loss: 3317.3654\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3311.7938 - val_loss: 3316.1204\n", "Epoch 59/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3301.7824 - val_loss: 3315.7516\n", + "409/409 [==============================] - 19s 47ms/step - loss: 3311.2996 - val_loss: 3312.3311\n", "Epoch 60/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3303.2513 - val_loss: 3312.9786\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3308.5555 - val_loss: 3307.4777\n", "Epoch 61/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3300.7803 - val_loss: 3311.4144\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3305.6500 - val_loss: 3309.9833\n", "Epoch 62/100\n", - "712/712 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val_loss: 3300.6306\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3288.7586 - val_loss: 3296.1178\n", "Epoch 80/100\n", - "712/712 [==============================] - 31s 43ms/step - loss: 3285.7712 - val_loss: 3299.9983\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3286.6697 - val_loss: 3296.9410\n", "Epoch 81/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3284.2461 - val_loss: 3300.0932\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3284.5288 - val_loss: 3293.2208\n", "Epoch 82/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3284.7717 - val_loss: 3302.6292\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3284.4468 - val_loss: 3293.6249\n", "Epoch 83/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3284.1242 - val_loss: 3301.5011\n", + "409/409 [==============================] - 19s 46ms/step - loss: 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[==============================] - 30s 42ms/step - loss: 3280.5820 - val_loss: 3298.0466\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3280.3106 - val_loss: 3292.8847\n", "Epoch 89/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3282.3804 - val_loss: 3300.0750\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3282.5400 - val_loss: 3288.2698\n", "Epoch 90/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3278.2497 - val_loss: 3303.1893\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3280.5732 - val_loss: 3289.8661\n", "Epoch 91/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3278.8160 - val_loss: 3301.6899\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3279.6276 - val_loss: 3293.7830\n", "Epoch 92/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3279.2742 - val_loss: 3299.9810\n", + 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3286.1671\n", "Epoch 97/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3276.6493 - val_loss: 3297.4587\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3275.5169 - val_loss: 3294.6421\n", "Epoch 98/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3274.3360 - val_loss: 3295.7449\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3271.4249 - val_loss: 3286.9777\n", "Epoch 99/100\n", - "712/712 [==============================] - 30s 42ms/step - loss: 3272.5990 - val_loss: 3298.1254\n", + "409/409 [==============================] - 19s 46ms/step - loss: 3274.3192 - val_loss: 3289.4395\n", "Epoch 100/100\n", - "712/712 [==============================] - 30s 43ms/step - loss: 3272.0184 - val_loss: 3302.1048\n" + "409/409 [==============================] - 19s 46ms/step - loss: 3273.1689 - val_loss: 3286.9439\n" ] }, { "data": { - "image/png": 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\n", 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\n", 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" ] diff --git a/pseudomonas_analysis/2_identify_generic_genes_pathways.ipynb b/pseudomonas_analysis/2_identify_generic_genes_pathways.ipynb index 8d96ccda..be005bd8 100644 --- a/pseudomonas_analysis/2_identify_generic_genes_pathways.ipynb +++ b/pseudomonas_analysis/2_identify_generic_genes_pathways.ipynb @@ -142,12 +142,12 @@ "gene_summary_filename = os.path.join(\n", " base_dir, \n", " dataset_name, \n", - " f\"generic_gene_summary_{project_id}_test.tsv\"\n", + " f\"generic_gene_summary_{project_id}.tsv\"\n", ")\n", "pathway_summary_filename = os.path.join(\n", " base_dir, \n", " dataset_name, \n", - " f\"generic_pathway_summary_{project_id}_test.tsv\"\n", + " f\"generic_pathway_summary_{project_id}.tsv\"\n", ")" ] }, @@ -171,15 +171,14 @@ "metadata": {}, "outputs": [ { - "name": "stdout", - "output_type": "stream", - "text": [ - "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/tensorflow_core/python/ops/resource_variable_ops.py:1630: calling BaseResourceVariable.__init__ (from tensorflow.python.ops.resource_variable_ops) with constraint is deprecated and will be removed in a future version.\n", - "Instructions for updating:\n", - "If using Keras pass *_constraint arguments to layers.\n", - "WARNING:tensorflow:From /home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/keras/backend/tensorflow_backend.py:422: The name tf.global_variables is deprecated. Please use tf.compat.v1.global_variables instead.\n", - "\n" - ] + "data": { + "text/plain": [ + "'# Simulate multiple experiments\\n# This step creates the following files in \"/pseudo_experiment/\" directory: \\n# - selected_simulated_data_SRP012656_.txt\\n# - selected_simulated_encoded_data_SRP012656_.txt\\n# - template_normalized_data_SRP012656_test.txt\\n# in which \"\" is an integer in the range of [0, num_runs-1] \\nos.makedirs(os.path.join(local_dir, \"pseudo_experiment\"), exist_ok=True)\\nfor run_id in range(num_runs):\\n simulate_expression_data.shift_template_experiment(\\n normalized_compendium_filename,\\n project_id,\\n metadata_col_id,\\n NN_architecture,\\n dataset_name,\\n scaler,\\n local_dir,\\n base_dir,\\n run_id)'" + ] + }, + "execution_count": 5, + "metadata": {}, + "output_type": "execute_result" } ], "source": [ @@ -219,36 +218,14 @@ "metadata": {}, "outputs": [ { - "name": "stdout", - "output_type": "stream", - "text": [ - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n", - "sample ids are ordered correctly\n" - ] + "data": { + "text/plain": [ + "'if not os.path.exists(sample_id_metadata_filename):\\n sample_id_metadata_filename = None\\n\\nstats.process_samples_for_limma(\\n raw_template_filename,\\n metadata_filename,\\n processed_template_filename,\\n sample_id_metadata_filename,\\n)\\n\\nfor i in range(num_runs):\\n simulated_filename = os.path.join(\\n local_dir,\\n \"pseudo_experiment\",\\n f\"selected_simulated_data_{project_id}_{i}.txt\"\\n )\\n stats.process_samples_for_limma(\\n simulated_filename,\\n metadata_filename,\\n None,\\n sample_id_metadata_filename,\\n)'" + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" } ], "source": [ @@ -909,6 +886,108 @@ "summary_gene_ranks.to_csv(gene_summary_filename, sep='\\t')" ] }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## Compare gene ranking" + ] + }, + { + "cell_type": "code", + "execution_count": 16, + "metadata": { + "scrolled": false + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "r = 0.44880008139441796\n", + "p = 2.8537129367217363e-273\n", + "ci_low = 0.4247636166550418\n", + "ci_high = 0.4699706464271449\n" + ] + }, + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/scipy/stats/stats.py:1713: FutureWarning: Using a non-tuple sequence for multidimensional indexing is deprecated; use `arr[tuple(seq)]` instead of `arr[seq]`. In the future this will be interpreted as an array index, `arr[np.array(seq)]`, which will result either in an error or a different result.\n", + " return np.add.reduce(sorted[indexer] * weights, axis=axis) / sumval\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/matplotlib/font_manager.py:1238: UserWarning: findfont: Font family ['Verdana'] not found. Falling back to DejaVu Sans.\n", + " (prop.get_family(), self.defaultFamily[fontext]))\n" + ] + }, + { + "data": { + "image/png": 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\n", + "text/plain": [ + "
" + ] + }, + "metadata": { + "needs_background": "light" + }, + "output_type": "display_data" + } + ], + "source": [ + "# Get generic genes identified by Crow et. al.\n", + "GAPE_filename = params['reference_gene_filename']\n", + "ref_gene_col = params['reference_gene_name_col']\n", + "ref_rank_col = params['reference_rank_col']\n", + "\n", + "figure_filename = f\"gene_ranking_{col_to_rank_genes}.svg\"\n", + "\n", + "corr, shared_ranking = ranking.compare_gene_ranking(\n", + " summary_gene_ranks,\n", + " GAPE_filename,\n", + " ref_gene_col,\n", + " ref_rank_col,\n", + " figure_filename\n", + ")" + ] + }, + { + "cell_type": "code", + "execution_count": 17, + "metadata": {}, + "outputs": [], + "source": [ + "# Get genes that are highly generic in both\n", + "generic_both = shared_ranking[(shared_ranking[\"Rank (simulated)\"]>4500) & (shared_ranking[\"prop DEGs\"]>3500)]\n", + "generic_both.to_csv(os.path.join(local_dir, \"SOPHIE_GAPE_generic.tsv\"), sep=\"\\t\")" + ] + }, + { + "cell_type": "code", + "execution_count": 18, + "metadata": {}, + "outputs": [], + "source": [ + "# Get genes that are highly generic by SOPHIE but not by GAPE\n", + "generic_SOPHIE_only = shared_ranking[(shared_ranking[\"Rank (simulated)\"]>4500) & (shared_ranking[\"prop DEGs\"]<2000)]\n", + "generic_SOPHIE_only.to_csv(os.path.join(local_dir, \"SOPHIE_generic_only.tsv\"), sep=\"\\t\")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "**Takeaway:**\n", + "\n", + "* X-axis: gene ranking using SOPHIE (trained on Pseudomonas compendium containing ~1K experiments)\n", + "* Y-axis: gene ranking using GAPE (curated set of 73 experiments)\n", + "\n", + "* Overall there is good consistency between SOPHIE and the reference set of experiments. There is especially more consistency amongst lowly ranked genes (genes that consistently didn’t change or genes that changed in a subset of cases). Perhaps the signal from these low ranked genes are very robust in P. aeruginosa\n", + " * Housekeeping genes make sense as contributing to a very strong consistent signal.\n", + " * What about those inconsistently DE genes? Assuming the 73 contexts are represented in the compendium, then those genes that are in consisten\n", + "* There is some noise in the bottom right corner (i.e. genes that the reference didn't think were as generic but SOPHIE did). These might be the result of the reference being limited to 73 experiments and differences in data processing (ANOVA vs RMA).\n", + " * Assuming the 73 contexts are represented in the compendium, if a gene is generic in the compendium, then this gene was found to be DE across many contexts, including the subset of 73 contexts. We suspect the reason for generic genes being highly generic in the compendium but NOT in the 73 experiments is because the signal to noise ratio will be lower in the smaller subset that reduce the generic signal." + ] + }, { "cell_type": "markdown", "metadata": {}, @@ -923,17 +1002,17 @@ }, { "cell_type": "code", - "execution_count": 16, + "execution_count": 19, "metadata": {}, "outputs": [], "source": [ "# Create \"/GSEA_stats/\" subdirectory\n", - "os.makedirs(os.path.join(local_dir, \"GSEA_stats\"), exist_ok=True)" + "os.makedirs(os.path.join(local_dir, \"GSA_stats\"), exist_ok=True)" ] }, { "cell_type": "code", - "execution_count": 17, + "execution_count": 20, "metadata": {}, "outputs": [], "source": [ @@ -943,7 +1022,7 @@ }, { "cell_type": "code", - "execution_count": 18, + "execution_count": 21, "metadata": {}, "outputs": [], "source": [ @@ -962,7 +1041,7 @@ }, { "cell_type": "code", - "execution_count": 19, + "execution_count": 22, "metadata": { "scrolled": false }, @@ -983,12 +1062,20 @@ "%%R -i base_dir -i template_DE_stats_filename -i adage_kegg_DB_processed_filename -i statistic -o template_enriched_pathways\n", "\n", "source(paste0(base_dir, '/generic_expression_patterns_modules/GSEA_analysis.R'))\n", - "template_enriched_pathways <- find_enriched_pathways(template_DE_stats_filename, adage_kegg_DB_processed_filename, statistic)" + "\n", + "out_filename <- paste(local_dir, \n", + " \"GSA_stats/GSEA_stats_template_data_\",\n", + " project_id,\n", + " \"_real.txt\", \n", + " sep = \"\")\n", + "\n", + "template_enriched_pathways <- find_enriched_pathways(template_DE_stats_filename, adage_kegg_DB_processed_filename, statistic)\n", + "write.table(as.data.frame(template_enriched_pathways[1:7]), file = out_filename, row.names = F, sep = \"\\t\")" ] }, { "cell_type": "code", - "execution_count": 20, + "execution_count": 23, "metadata": { "scrolled": true }, @@ -1036,55 +1123,55 @@ " 168\n", " KEGG-Module-M00178: Ribosome, bacteria\n", " 0.000113\n", - " 0.001157\n", + " 0.001271\n", " 0.914364\n", - " 6.117751\n", + " 6.108502\n", " 0.0\n", " 55\n", " None\n", " \n", " \n", - " 91\n", - " KEGG-Pathway-pae00010: Glycolysis / Gluconeoge...\n", - " 0.000120\n", - " 0.001157\n", - " 0.451513\n", - " 2.578504\n", + " 50\n", + " KEGG-Pathway-pae03010: Ribosome - Pseudomonas ...\n", + " 0.000113\n", + " 0.001271\n", + " 0.914364\n", + " 6.108502\n", " 0.0\n", - " 35\n", + " 55\n", " None\n", " \n", " \n", - " 74\n", - " KEGG-Pathway-pae00680: Methane metabolism - Ps...\n", - " 0.000128\n", - " 0.001157\n", - " 0.550329\n", - " 2.716780\n", + " 49\n", + " KEGG-Pathway-pae03018: RNA degradation - Pseud...\n", + " 0.000138\n", + " 0.001271\n", + " 0.700591\n", + " 2.796353\n", " 0.0\n", - " 24\n", + " 14\n", " None\n", " \n", " \n", - " 70\n", - " KEGG-Pathway-pae00250: Alanine, aspartate and ...\n", - " 0.000121\n", - " 0.001157\n", - " 0.471680\n", - " 2.661697\n", + " 48\n", + " KEGG-Pathway-pae00330: Arginine and proline me...\n", + " 0.000110\n", + " 0.001271\n", + " 0.362552\n", + " 2.609733\n", " 0.0\n", - " 34\n", + " 69\n", " None\n", " \n", " \n", - " 61\n", - " KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth...\n", + " 47\n", + " KEGG-Pathway-pae00030: Pentose phosphate pathw...\n", " 0.000127\n", - " 0.001157\n", - " 0.669514\n", - " 3.410769\n", + " 0.001271\n", + " 0.533769\n", + " 2.640694\n", " 0.0\n", - " 26\n", + " 24\n", " None\n", " \n", " \n", @@ -1093,21 +1180,21 @@ ], "text/plain": [ " pathway pval padj \\\n", - "168 KEGG-Module-M00178: Ribosome, bacteria 0.000113 0.001157 \n", - "91 KEGG-Pathway-pae00010: Glycolysis / Gluconeoge... 0.000120 0.001157 \n", - "74 KEGG-Pathway-pae00680: Methane metabolism - Ps... 0.000128 0.001157 \n", - "70 KEGG-Pathway-pae00250: Alanine, aspartate and ... 0.000121 0.001157 \n", - "61 KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth... 0.000127 0.001157 \n", + "168 KEGG-Module-M00178: Ribosome, bacteria 0.000113 0.001271 \n", + "50 KEGG-Pathway-pae03010: Ribosome - Pseudomonas ... 0.000113 0.001271 \n", + "49 KEGG-Pathway-pae03018: RNA degradation - Pseud... 0.000138 0.001271 \n", + "48 KEGG-Pathway-pae00330: Arginine and proline me... 0.000110 0.001271 \n", + "47 KEGG-Pathway-pae00030: Pentose phosphate pathw... 0.000127 0.001271 \n", "\n", " ES NES nMoreExtreme size leadingEdge \n", - "168 0.914364 6.117751 0.0 55 None \n", - "91 0.451513 2.578504 0.0 35 None \n", - "74 0.550329 2.716780 0.0 24 None \n", - "70 0.471680 2.661697 0.0 34 None \n", - "61 0.669514 3.410769 0.0 26 None " + "168 0.914364 6.108502 0.0 55 None \n", + "50 0.914364 6.108502 0.0 55 None \n", + "49 0.700591 2.796353 0.0 14 None \n", + "48 0.362552 2.609733 0.0 69 None \n", + "47 0.533769 2.640694 0.0 24 None " ] }, - "execution_count": 20, + "execution_count": 23, "metadata": {}, "output_type": "execute_result" } @@ -1119,7 +1206,7 @@ }, { "cell_type": "code", - "execution_count": 21, + "execution_count": 24, "metadata": {}, "outputs": [], "source": [ @@ -1138,7 +1225,7 @@ " sep = \"\")\n", " \n", " out_filename <- paste(local_dir, \n", - " \"GSEA_stats/GSEA_stats_simulated_data_\",\n", + " \"GSA_stats/GSEA_stats_simulated_data_\",\n", " project_id,\n", " \"_\",\n", " i,\n", @@ -1161,14 +1248,14 @@ }, { "cell_type": "code", - "execution_count": 22, + "execution_count": 25, "metadata": {}, "outputs": [], "source": [ - "analysis_type = \"GSEA\"\n", + "analysis_type = \"GSA\"\n", "template_GSEA_stats_filename = os.path.join(\n", " local_dir,\n", - " \"GSEA_stats\",\n", + " \"GSA_stats\",\n", " f\"GSEA_stats_template_data_{project_id}_real.txt\" \n", ")\n", "template_GSEA_stats, simulated_GSEA_summary_stats = ranking.process_and_rank_genes_pathways(\n", @@ -1178,6 +1265,7 @@ " project_id,\n", " analysis_type,\n", " col_to_rank_pathways,\n", + " \"GSEA\"\n", ")" ] }, @@ -1190,9 +1278,17 @@ }, { "cell_type": "code", - "execution_count": 23, + "execution_count": 26, "metadata": {}, "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/pandas/core/reshape/merge.py:544: UserWarning: merging between different levels can give an unintended result (1 levels on the left, 2 on the right)\n", + " warnings.warn(msg, UserWarning)\n" + ] + }, { "data": { "text/html": [ @@ -1243,67 +1339,67 @@ " \n", " KEGG-Module-M00178: Ribosome, bacteria\n", " KEGG-Module-M00178: Ribosome, bacteria\n", - " 0.001249\n", - " 159.0\n", - " 0.001249\n", - " 0.001238\n", - " 161.5\n", - " 0.001307\n", - " 0.000257\n", + " 0.001271\n", + " 159.5\n", + " 0.001271\n", + " 0.001355\n", + " 162.0\n", + " 0.001335\n", + " 0.000233\n", " 25\n", - " -0.223324\n", + " -0.274735\n", " \n", " \n", - " KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1\n", - " KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth...\n", - " 0.001249\n", - " 159.0\n", - " 0.001249\n", - " 0.001238\n", - " 161.5\n", - " 0.001307\n", - " 0.000257\n", + " KEGG-Pathway-pae00240: Pyrimidine metabolism - Pseudomonas aeruginosa PAO1\n", + " KEGG-Pathway-pae00240: Pyrimidine metabolism -...\n", + " 0.001271\n", + " 159.5\n", + " 0.001271\n", + " 0.001355\n", + " 162.0\n", + " 0.001335\n", + " 0.000233\n", " 25\n", - " -0.223324\n", + " -0.274735\n", " \n", " \n", - " KEGG-Module-M00011: Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate\n", - " KEGG-Module-M00011: Citrate cycle, second carb...\n", - " 0.001249\n", - " 159.0\n", - " 0.001249\n", - " 0.001238\n", - " 161.5\n", - " 0.001345\n", - " 0.000405\n", + " KEGG-Pathway-pae00190: Oxidative phosphorylation - Pseudomonas aeruginosa PAO1\n", + " KEGG-Pathway-pae00190: Oxidative phosphorylati...\n", + " 0.001271\n", + " 159.5\n", + " 0.001271\n", + " 0.001355\n", + " 162.0\n", + " 0.001335\n", + " 0.000233\n", " 25\n", - " -0.236316\n", + " -0.274735\n", " \n", " \n", - " KEGG-Module-M00335: Sec (secretion) system\n", - " KEGG-Module-M00335: Sec (secretion) system\n", - " 0.001249\n", - " 159.0\n", - " 0.001249\n", - " 0.001238\n", - " 161.5\n", - " 0.001599\n", - " 0.001568\n", + " KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1\n", + " KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth...\n", + " 0.001271\n", + " 159.5\n", + " 0.001271\n", + " 0.001355\n", + " 162.0\n", + " 0.001335\n", + " 0.000233\n", " 25\n", - " -0.223061\n", + " -0.274735\n", " \n", " \n", " KEGG-Module-M00009: Citrate cycle (TCA cycle, Krebs cycle)\n", " KEGG-Module-M00009: Citrate cycle (TCA cycle, ...\n", - " 0.001249\n", - " 159.0\n", - " 0.001249\n", - " 0.001238\n", - " 161.5\n", - " 0.001307\n", - " 0.000257\n", + " 0.001271\n", + " 159.5\n", + " 0.001271\n", + " 0.001355\n", + " 162.0\n", + " 0.001335\n", + " 0.000233\n", " 25\n", - " -0.223324\n", + " -0.274735\n", " \n", " \n", "\n", @@ -1313,77 +1409,77 @@ " Pathway ID \\\n", "pathway \n", "KEGG-Module-M00178: Ribosome, bacteria KEGG-Module-M00178: Ribosome, bacteria \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... KEGG-Pathway-pae00240: Pyrimidine metabolism -... \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... KEGG-Pathway-pae00190: Oxidative phosphorylati... \n", "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth... \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... KEGG-Module-M00011: Citrate cycle, second carb... \n", - "KEGG-Module-M00335: Sec (secretion) system KEGG-Module-M00335: Sec (secretion) system \n", "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... KEGG-Module-M00009: Citrate cycle (TCA cycle, ... \n", "\n", " Adj P-value (Real) \\\n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria 0.001249 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001249 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 0.001249 \n", - "KEGG-Module-M00335: Sec (secretion) system 0.001249 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.001249 \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.001271 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 0.001271 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.001271 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001271 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.001271 \n", "\n", " Rank (Real) padj (Real) \\\n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria 159.0 0.001249 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 159.0 0.001249 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 159.0 0.001249 \n", - "KEGG-Module-M00335: Sec (secretion) system 159.0 0.001249 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 159.0 0.001249 \n", + "KEGG-Module-M00178: Ribosome, bacteria 159.5 0.001271 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 159.5 0.001271 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 159.5 0.001271 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 159.5 0.001271 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 159.5 0.001271 \n", "\n", " Median adj p-value (simulated) \\\n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria 0.001238 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001238 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 0.001238 \n", - "KEGG-Module-M00335: Sec (secretion) system 0.001238 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.001238 \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.001355 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 0.001355 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.001355 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001355 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.001355 \n", "\n", " Rank (simulated) \\\n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria 161.5 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 161.5 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 161.5 \n", - "KEGG-Module-M00335: Sec (secretion) system 161.5 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 161.5 \n", + "KEGG-Module-M00178: Ribosome, bacteria 162.0 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 162.0 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 162.0 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 162.0 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 162.0 \n", "\n", " Mean padj (simulated) \\\n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria 0.001307 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001307 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 0.001345 \n", - "KEGG-Module-M00335: Sec (secretion) system 0.001599 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.001307 \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.001335 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 0.001335 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.001335 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001335 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.001335 \n", "\n", " Std deviation (simulated) \\\n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria 0.000257 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.000257 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 0.000405 \n", - "KEGG-Module-M00335: Sec (secretion) system 0.001568 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.000257 \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.000233 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 0.000233 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.000233 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.000233 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 0.000233 \n", "\n", " Number of experiments (simulated) \\\n", "pathway \n", "KEGG-Module-M00178: Ribosome, bacteria 25 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... 25 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 25 \n", "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 25 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... 25 \n", - "KEGG-Module-M00335: Sec (secretion) system 25 \n", "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... 25 \n", "\n", " Z score \n", "pathway \n", - "KEGG-Module-M00178: Ribosome, bacteria -0.223324 \n", - "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... -0.223324 \n", - "KEGG-Module-M00011: Citrate cycle, second carbo... -0.236316 \n", - "KEGG-Module-M00335: Sec (secretion) system -0.223061 \n", - "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... -0.223324 " + "KEGG-Module-M00178: Ribosome, bacteria -0.274735 \n", + "KEGG-Pathway-pae00240: Pyrimidine metabolism - ... -0.274735 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... -0.274735 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... -0.274735 \n", + "KEGG-Module-M00009: Citrate cycle (TCA cycle, K... -0.274735 " ] }, - "execution_count": 23, + "execution_count": 26, "metadata": {}, "output_type": "execute_result" } @@ -1405,7 +1501,7 @@ }, { "cell_type": "code", - "execution_count": 24, + "execution_count": 27, "metadata": {}, "outputs": [], "source": [ diff --git a/pseudomonas_analysis/2_identify_generic_genes_pathways_pao1.ipynb b/pseudomonas_analysis/2_identify_generic_genes_pathways_pao1.ipynb new file mode 100644 index 00000000..6db4ab78 --- /dev/null +++ b/pseudomonas_analysis/2_identify_generic_genes_pathways_pao1.ipynb @@ -0,0 +1,1760 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "# Identify generic genes and pathways using subset of training compendium\n", + "\n", + "Studies have found that some genes are more likely to be differentially expressed even across a wide range of experimental designs. These generic genes and subsequent pathways are not necessarily specific to the biological process being studied but instead represent a more systematic change. \n", + "\n", + "We have developed an approach, outlined below, to automatically identify these generic genes and pathways. We have validated this simulation approach can identify generic genes and pathways in the analysis notebooks: [human_general_analysis](../human_general_analysis/) and [human_cancer_analysis](../human_cancer_analysis/). Here\n", + "\n", + "This notebook applies this approach to identify generic genes and pathways in the pseudomonas compendium. \n", + "\n", + "**Steps to identify generic genes:**\n", + "1. Simulates N gene expression experiments using [ponyo](https://github.com/ajlee21/ponyo)\n", + "2. Perform DE analysis to get association statistics for each gene\n", + "\n", + "In this case the DE analysis is based on the experimental design of the template experiment, described in the previous [notebook](1_process_pseudomonas_data.ipynb). \n", + "The template experiment is [GEOD-33245](https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-33245/?s_sortby=col_8&s_sortorder=ascending), which contains multiple different comparisons including WT vs *crc* mutants, WT vs *cbr* mutants in different conditions. So the DE analysis is comparing WT vs mutant.\n", + "\n", + "3. For each gene, aggregate statistics across all simulated experiments \n", + "4. Rank genes based on this aggregated statistic\n", + "\n", + "**Steps to identify generic gene sets (pathways):**\n", + "1. Using the same simulated experiments from above, perform GSEA analysis. This analysis will determine whether the genes contained in a gene set are clustered towards the beginning or the end of the ranked list of genes, where genes are ranked by log fold change, indicating a correlation with change in expression.\n", + "2. For each gene set (pathway), aggregate statistics across all simulated experiments\n", + "3. Rank gene sets based on this aggregated statistic" + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/matplotlib/__init__.py:886: MatplotlibDeprecationWarning: \n", + "examples.directory is deprecated; in the future, examples will be found relative to the 'datapath' directory.\n", + " \"found relative to the 'datapath' directory.\".format(key))\n", + "Using TensorFlow backend.\n" + ] + } + ], + "source": [ + "%load_ext autoreload\n", + "%load_ext rpy2.ipython\n", + "%autoreload 2\n", + "\n", + "import os\n", + "import sys\n", + "import glob\n", + "import pandas as pd\n", + "import numpy as np\n", + "import seaborn as sns\n", + "import pickle\n", + "\n", + "from rpy2.robjects import pandas2ri\n", + "pandas2ri.activate()\n", + "\n", + "from ponyo import utils, simulate_expression_data\n", + "from generic_expression_patterns_modules import process, stats, ranking\n", + "\n", + "np.random.seed(123)" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "metadata": {}, + "outputs": [], + "source": [ + "# Read in config variables\n", + "base_dir = os.path.abspath(os.path.join(os.getcwd(),\"../\"))\n", + "\n", + "config_filename = os.path.abspath(os.path.join(base_dir,\n", + " \"configs\",\n", + " \"config_pseudomonas_pao1.tsv\"))\n", + "params = utils.read_config(config_filename)" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "metadata": {}, + "outputs": [], + "source": [ + "# Load params\n", + "local_dir = params[\"local_dir\"]\n", + "dataset_name = params['dataset_name']\n", + "NN_architecture = params['NN_architecture']\n", + "num_runs = params['num_simulated']\n", + "project_id = params['project_id']\n", + "metadata_col_id = params['metadata_colname']\n", + "raw_template_filename = params['raw_template_filename']\n", + "processed_template_filename = params['processed_template_filename']\n", + "normalized_compendium_filename = params['normalized_compendium_filename']\n", + "scaler_filename = params['scaler_filename']\n", + "col_to_rank_genes = params['rank_genes_by']\n", + "col_to_rank_pathways = params['rank_pathways_by']\n", + "statistic = params['gsea_statistic']\n", + "\n", + "# Load metadata file with grouping assignments for samples\n", + "sample_id_metadata_filename = os.path.join(\n", + " base_dir,\n", + " dataset_name,\n", + " \"data\",\n", + " \"metadata\",\n", + " f\"{project_id}_process_samples.tsv\")\n", + "\n", + "# Load metadata file with grouping assignments for samples\n", + "metadata_filename = os.path.join(\n", + " base_dir,\n", + " dataset_name,\n", + " \"data\",\n", + " \"metadata\",\n", + " f\"{project_id}_groups.tsv\"\n", + ")\n", + "\n", + "# Load pickled file\n", + "scaler = pickle.load(open(scaler_filename, \"rb\"))" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "metadata": {}, + "outputs": [], + "source": [ + "# Output files\n", + "gene_summary_filename = os.path.join(\n", + " base_dir, \n", + " dataset_name, \n", + " f\"generic_gene_summary_{project_id}_pao1.tsv\"\n", + ")\n", + "pathway_summary_filename = os.path.join(\n", + " base_dir, \n", + " dataset_name, \n", + " f\"generic_pathway_summary_{project_id}_pao1.tsv\"\n", + ")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Simulate experiments using selected template experiment\n", + "Workflow:\n", + "\n", + "1. Get the gene expression data for the selected template experiment\n", + "2. Encode this experiment into a latent space using the trained VAE model\n", + "3. Linearly shift the encoded template experiment in the latent space\n", + "4. Decode the samples. This results in a new experiment\n", + "5. Repeat steps 1-4 to get multiple simulated experiments" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "metadata": {}, + "outputs": [], + "source": [ + "# Note: We are manually changing the function to suit our nex experiment where we \n", + "# subset our training compendium. Ponyo will be updated to address this change to\n", + "# be more robust to user inputs\n", + "import glob\n", + "import warnings\n", + "from keras.models import load_model\n", + "from sklearn import preprocessing\n", + "\n", + "def get_sample_ids(experiment_id, dataset_name, sample_id_colname):\n", + " \"\"\"\n", + " Returns sample ids (found in gene expression df) associated with\n", + " a given list of experiment ids (found in the metadata)\n", + "\n", + " Arguments\n", + " ----------\n", + " experiment_ids_file: str\n", + " File containing all cleaned experiment ids\n", + "\n", + " dataset_name: str\n", + " Name for analysis directory. Either \"Human\" or \"Pseudomonas\"\n", + "\n", + " sample_id_colname: str\n", + " Column header that contains sample id that maps expression data\n", + " and metadata\n", + "\n", + " \"\"\"\n", + " base_dir = os.path.abspath(os.path.join(os.getcwd(), \"../\"))\n", + "\n", + " if \"pseudomonas\" in dataset_name.lower():\n", + " # metadata file\n", + " mapping_file = os.path.join(\n", + " base_dir, dataset_name, \"data\", \"metadata\", \"sample_annotations.tsv\"\n", + " )\n", + "\n", + " # Read in metadata\n", + " metadata = pd.read_csv(mapping_file, header=0, sep=\"\\t\", index_col=0)\n", + "\n", + " selected_metadata = metadata.loc[experiment_id]\n", + " sample_ids = list(selected_metadata[sample_id_colname])\n", + "\n", + " else:\n", + " # metadata file\n", + " mapping_file = os.path.join(\n", + " base_dir, dataset_name, \"data\", \"metadata\", \"recount2_metadata.tsv\"\n", + " )\n", + "\n", + " # Read in metadata\n", + " metadata = pd.read_csv(mapping_file, header=0, sep=\"\\t\", index_col=0)\n", + "\n", + " selected_metadata = metadata.loc[experiment_id]\n", + " sample_ids = list(selected_metadata[sample_id_colname])\n", + "\n", + " return sample_ids\n", + "\n", + "def shift_template_experiment_tmp(\n", + " normalized_data_file,\n", + " selected_experiment_id,\n", + " sample_id_colname,\n", + " NN_architecture,\n", + " dataset_name,\n", + " scaler,\n", + " local_dir,\n", + " base_dir,\n", + " run,\n", + "):\n", + " \"\"\"\n", + " Generate new simulated experiment using the selected_experiment_id as a template\n", + " experiment and shifting this template experiment in the latent space to a new\n", + " location. This shifted experiment will be the new simulated experiment.\n", + "\n", + " This will return a file with a single simulated experiment following the workflow mentioned.\n", + " This function can be run multiple times to generate multiple simulated experiments from a\n", + " single selected_experiment_id.\n", + "\n", + " Arguments\n", + " ----------\n", + " normalized_data_file: str\n", + " File containing normalized gene expression data\n", + "\n", + " ------------------------------| PA0001 | PA0002 |...\n", + " 05_PA14000-4-2_5-10-07_S2.CEL | 0.8533 | 0.7252 |...\n", + " 54375-4-05.CEL | 0.7789 | 0.7678 |...\n", + " ... | ... | ... |...\n", + "\n", + " selected_experiment_id: str\n", + " Experiment id selected as template\n", + "\n", + " sample_id_colname: str\n", + " Column header that contains sample id that maps expression data and metadata\n", + "\n", + " NN_architecture: str\n", + " Name of neural network architecture to use.\n", + " Format 'NN__'\n", + "\n", + " dataset_name: str\n", + " Name for analysis directory. Either \"Human\" or \"Pseudomonas\"\n", + "\n", + " scaler: minmax model\n", + " Model used to transform data into a different range\n", + "\n", + " local_dir: str\n", + " Parent directory on local machine to store intermediate results\n", + "\n", + " base_dir: str\n", + " Root directory containing analysis subdirectories\n", + "\n", + " run: int\n", + " Simulation run\n", + "\n", + " Returns\n", + " --------\n", + " simulated_data_file: str\n", + " File containing simulated gene expression data\n", + "\n", + " \"\"\"\n", + "\n", + " # Files\n", + " NN_dir = os.path.join(base_dir, dataset_name, \"models\", NN_architecture)\n", + " latent_dim = NN_architecture.split(\"_\")[-2] # Here we manually changed the index to work\n", + "\n", + " model_encoder_file = glob.glob(os.path.join(NN_dir, \"*_encoder_model.h5\"))[0]\n", + "\n", + " weights_encoder_file = glob.glob(os.path.join(NN_dir, \"*_encoder_weights.h5\"))[0]\n", + "\n", + " model_decoder_file = glob.glob(os.path.join(NN_dir, \"*_decoder_model.h5\"))[0]\n", + "\n", + " weights_decoder_file = glob.glob(os.path.join(NN_dir, \"*_decoder_weights.h5\"))[0]\n", + "\n", + " # Load saved models\n", + " loaded_model = load_model(model_encoder_file, compile=False)\n", + " loaded_decode_model = load_model(model_decoder_file, compile=False)\n", + "\n", + " loaded_model.load_weights(weights_encoder_file)\n", + " loaded_decode_model.load_weights(weights_decoder_file)\n", + "\n", + " # Read data\n", + " normalized_data = pd.read_csv(normalized_data_file, header=0, sep=\"\\t\", index_col=0)\n", + "\n", + " # Get corresponding sample ids\n", + " sample_ids = get_sample_ids(selected_experiment_id, dataset_name, sample_id_colname)\n", + "\n", + " # Gene expression data for selected samples\n", + " selected_data_df = normalized_data.loc[sample_ids]\n", + "\n", + " # Encode selected experiment into latent space\n", + " data_encoded = loaded_model.predict_on_batch(selected_data_df)\n", + " data_encoded_df = pd.DataFrame(data_encoded, index=selected_data_df.index)\n", + "\n", + " # Get centroid of original data\n", + " centroid = data_encoded_df.mean(axis=0)\n", + "\n", + " # Add individual vectors(centroid, sample point) to new_centroid\n", + "\n", + " # Encode original gene expression data into latent space\n", + " data_encoded_all = loaded_model.predict_on_batch(normalized_data)\n", + " data_encoded_all_df = pd.DataFrame(data_encoded_all, index=normalized_data.index)\n", + "\n", + " data_encoded_all_df.head()\n", + "\n", + " # Find a new location in the latent space by sampling from the latent space\n", + " encoded_means = data_encoded_all_df.mean(axis=0)\n", + " encoded_stds = data_encoded_all_df.std(axis=0)\n", + "\n", + " latent_dim = int(latent_dim)\n", + " new_centroid = np.zeros(latent_dim)\n", + "\n", + " for j in range(latent_dim):\n", + " new_centroid[j] = np.random.normal(encoded_means[j], encoded_stds[j])\n", + "\n", + " shift_vec_df = new_centroid - centroid\n", + "\n", + " simulated_data_encoded_df = data_encoded_df.apply(\n", + " lambda x: x + shift_vec_df, axis=1\n", + " )\n", + "\n", + " # Decode simulated data into raw gene space\n", + " simulated_data_decoded = loaded_decode_model.predict_on_batch(\n", + " simulated_data_encoded_df\n", + " )\n", + "\n", + " simulated_data_decoded_df = pd.DataFrame(\n", + " simulated_data_decoded,\n", + " index=simulated_data_encoded_df.index,\n", + " columns=selected_data_df.columns,\n", + " )\n", + "\n", + " # Un-normalize the data in order to run DE analysis downstream\n", + " simulated_data_scaled = scaler.inverse_transform(simulated_data_decoded_df)\n", + "\n", + " simulated_data_scaled_df = pd.DataFrame(\n", + " simulated_data_scaled,\n", + " columns=simulated_data_decoded_df.columns,\n", + " index=simulated_data_decoded_df.index,\n", + " )\n", + "\n", + " # Save template data for visualization validation\n", + " test_file = os.path.join(\n", + " local_dir,\n", + " \"pseudo_experiment\",\n", + " \"template_normalized_data_\" + selected_experiment_id + \"_test.txt\",\n", + " )\n", + "\n", + " selected_data_df.to_csv(test_file, float_format=\"%.3f\", sep=\"\\t\")\n", + "\n", + " # Save\n", + " out_file = os.path.join(\n", + " local_dir,\n", + " \"pseudo_experiment\",\n", + " \"selected_simulated_data_\" + selected_experiment_id + \"_\" + str(run) + \".txt\",\n", + " )\n", + "\n", + " simulated_data_scaled_df.to_csv(out_file, float_format=\"%.3f\", sep=\"\\t\")\n", + "\n", + " out_encoded_file = os.path.join(\n", + " local_dir,\n", + " \"pseudo_experiment\",\n", + " f\"selected_simulated_encoded_data_{selected_experiment_id}_{run}.txt\",\n", + " )\n", + "\n", + " simulated_data_encoded_df.to_csv(out_encoded_file, float_format=\"%.3f\", sep=\"\\t\")" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "'# Simulate multiple experiments\\n# This step creates the following files in \"/pseudo_experiment/\" directory: \\n# - selected_simulated_data_SRP012656_.txt\\n# - selected_simulated_encoded_data_SRP012656_.txt\\n# - template_normalized_data_SRP012656_test.txt\\n# in which \"\" is an integer in the range of [0, num_runs-1] \\nos.makedirs(os.path.join(local_dir, \"pseudo_experiment\"), exist_ok=True)\\nfor run_id in range(num_runs):\\n shift_template_experiment_tmp(\\n normalized_compendium_filename,\\n project_id,\\n metadata_col_id,\\n NN_architecture,\\n dataset_name,\\n scaler,\\n local_dir,\\n base_dir,\\n run_id)'" + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Simulate multiple experiments\n", + "# This step creates the following files in \"/pseudo_experiment/\" directory: \n", + "# - selected_simulated_data_SRP012656_.txt\n", + "# - selected_simulated_encoded_data_SRP012656_.txt\n", + "# - template_normalized_data_SRP012656_test.txt\n", + "# in which \"\" is an integer in the range of [0, num_runs-1] \n", + "os.makedirs(os.path.join(local_dir, \"pseudo_experiment\"), exist_ok=True)\n", + "for run_id in range(num_runs):\n", + " shift_template_experiment_tmp(\n", + " normalized_compendium_filename,\n", + " project_id,\n", + " metadata_col_id,\n", + " NN_architecture,\n", + " dataset_name,\n", + " scaler,\n", + " local_dir,\n", + " base_dir,\n", + " run_id)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Process template and simulated data\n", + "\n", + "* Remove samples not required for comparison. \n", + "* Make sure ordering of samples matches metadata for proper comparison" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "'if not os.path.exists(sample_id_metadata_filename):\\n sample_id_metadata_filename = None\\n\\nstats.process_samples_for_limma(\\n raw_template_filename,\\n metadata_filename,\\n processed_template_filename,\\n sample_id_metadata_filename,\\n)\\n\\nfor i in range(num_runs):\\n simulated_filename = os.path.join(\\n local_dir,\\n \"pseudo_experiment\",\\n f\"selected_simulated_data_{project_id}_{i}.txt\"\\n )\\n stats.process_samples_for_limma(\\n simulated_filename,\\n metadata_filename,\\n None,\\n sample_id_metadata_filename,\\n)'" + ] + }, + "execution_count": 7, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "if not os.path.exists(sample_id_metadata_filename):\n", + " sample_id_metadata_filename = None\n", + "\n", + "stats.process_samples_for_limma(\n", + " raw_template_filename,\n", + " metadata_filename,\n", + " processed_template_filename,\n", + " sample_id_metadata_filename,\n", + ")\n", + "\n", + "for i in range(num_runs):\n", + " simulated_filename = os.path.join(\n", + " local_dir,\n", + " \"pseudo_experiment\",\n", + " f\"selected_simulated_data_{project_id}_{i}.txt\"\n", + " )\n", + " stats.process_samples_for_limma(\n", + " simulated_filename,\n", + " metadata_filename,\n", + " None,\n", + " sample_id_metadata_filename,\n", + ")" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "metadata": {}, + "outputs": [], + "source": [ + "# Quick check\n", + "template_data = pd.read_csv(\n", + " processed_template_filename, \n", + " header=0,\n", + " index_col=0,\n", + " sep=\"\\t\"\n", + ")\n", + "\n", + "assert(template_data.shape[0] == 4)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Differential expression analysis" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "metadata": {}, + "outputs": [], + "source": [ + "# Create subdirectory: \"/DE_stats/\"\n", + "os.makedirs(os.path.join(local_dir, \"DE_stats\"), exist_ok=True)" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: Loading required 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To cite Bioconductor, see\n", + " 'citation(\"Biobase\")', and for packages 'citation(\"pkgname\")'.\n", + "\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: Loading required package: DelayedArray\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: Loading required package: matrixStats\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: \n", + "Attaching package: ‘matrixStats’\n", + "\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: The following objects are masked from ‘package:Biobase’:\n", + "\n", + " anyMissing, rowMedians\n", + "\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: Loading required package: BiocParallel\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: \n", + "Attaching package: ‘DelayedArray’\n", + "\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: The following objects are masked from ‘package:matrixStats’:\n", + "\n", + " colMaxs, colMins, colRanges, rowMaxs, rowMins, rowRanges\n", + "\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: The following objects are masked from ‘package:base’:\n", + "\n", + " aperm, apply, rowsum\n", + "\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n" + ] + }, + { + "data": { + "text/plain": [ + "[1] 15\n" + ] + }, + "metadata": {}, + "output_type": "display_data" + } + ], + "source": [ + "%%R -i metadata_filename -i project_id -i processed_template_filename -i local_dir -i base_dir\n", + "\n", + "source(paste0(base_dir, '/generic_expression_patterns_modules/DE_analysis.R'))\n", + "\n", + "get_DE_stats_limma(metadata_filename,\n", + " project_id, \n", + " processed_template_filename,\n", + " \"template\",\n", + " local_dir,\n", + " \"real\")" + ] + }, + { + "cell_type": "code", + "execution_count": 11, + "metadata": {}, + "outputs": [], + "source": [ + "%%R -i metadata_filename -i project_id -i base_dir -i local_dir -i num_runs -o num_sign_DEGs_simulated\n", + "\n", + "source(paste0(base_dir,'/generic_expression_patterns_modules/DE_analysis.R'))\n", + "\n", + "num_sign_DEGs_simulated <- c()\n", + "\n", + "for (i in 0:(num_runs-1)){\n", + " simulated_data_filename <- paste(\n", + " local_dir, \n", + " \"pseudo_experiment/selected_simulated_data_\",\n", + " project_id,\n", + " \"_\", \n", + " i,\n", + " \".txt\",\n", + " sep=\"\"\n", + " )\n", + " \n", + " run_output <- get_DE_stats_limma(\n", + " metadata_filename,\n", + " project_id, \n", + " simulated_data_filename,\n", + " \"simulated\",\n", + " local_dir,\n", + " i\n", + " )\n", + " num_sign_DEGs_simulated <- c(num_sign_DEGs_simulated, run_output)\n", + "}" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Rank genes" + ] + }, + { + "cell_type": "code", + "execution_count": 12, + "metadata": {}, + "outputs": [], + "source": [ + "analysis_type = \"DE\"\n", + "template_DE_stats_filename = os.path.join(\n", + " local_dir,\n", + " \"DE_stats\",\n", + " f\"DE_stats_template_data_{project_id}_real.txt\"\n", + ")\n", + "template_DE_stats, simulated_DE_summary_stats = ranking.process_and_rank_genes_pathways(\n", + " template_DE_stats_filename,\n", + " local_dir,\n", + " num_runs,\n", + " project_id,\n", + " analysis_type,\n", + " col_to_rank_genes,\n", + ")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Gene summary table" + ] + }, + { + "cell_type": "code", + "execution_count": 13, + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/pandas/core/reshape/merge.py:544: UserWarning: merging between different levels can give an unintended result (1 levels on the left, 2 on the right)\n", + " warnings.warn(msg, UserWarning)\n" + ] + }, + { + "data": { + "text/html": [ + "
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Gene IDAdj P-value (Real)Rank (Real)abs(logFC) (Real)logFC (Real)Median adj p-value (simulated)Rank (simulated)Mean abs(logFC) (simulated)Std deviation (simulated)Number of experiments (simulated)Z score
PA2195PA21950.0134045504.01.549834-1.5498340.7333403092.00.127540.0770982518.447771
PA4726PA47260.0000105549.04.530917-4.5309170.5547274636.50.248040.2429612517.627806
PA2260PA22600.0347415387.00.9536350.9536350.7417301713.00.089600.0507182517.036139
PA3915PA39150.0009205535.02.065593-2.0655930.3914125308.00.288700.1092852516.259220
PA5168PA51680.0051375475.01.292737-1.2927370.7072603344.50.138700.0751712515.352146
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" + ], + "text/plain": [ + " Gene ID Adj P-value (Real) Rank (Real) abs(logFC) (Real) \\\n", + "PA2195 PA2195 0.013404 5504.0 1.549834 \n", + "PA4726 PA4726 0.000010 5549.0 4.530917 \n", + "PA2260 PA2260 0.034741 5387.0 0.953635 \n", + "PA3915 PA3915 0.000920 5535.0 2.065593 \n", + "PA5168 PA5168 0.005137 5475.0 1.292737 \n", + "\n", + " logFC (Real) Median adj p-value (simulated) Rank (simulated) \\\n", + "PA2195 -1.549834 0.733340 3092.0 \n", + "PA4726 -4.530917 0.554727 4636.5 \n", + "PA2260 0.953635 0.741730 1713.0 \n", + "PA3915 -2.065593 0.391412 5308.0 \n", + "PA5168 -1.292737 0.707260 3344.5 \n", + "\n", + " Mean abs(logFC) (simulated) Std deviation (simulated) \\\n", + "PA2195 0.12754 0.077098 \n", + "PA4726 0.24804 0.242961 \n", + "PA2260 0.08960 0.050718 \n", + "PA3915 0.28870 0.109285 \n", + "PA5168 0.13870 0.075171 \n", + "\n", + " Number of experiments (simulated) Z score \n", + "PA2195 25 18.447771 \n", + "PA4726 25 17.627806 \n", + "PA2260 25 17.036139 \n", + "PA3915 25 16.259220 \n", + "PA5168 25 15.352146 " + ] + }, + "execution_count": 13, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "summary_gene_ranks = ranking.generate_summary_table(\n", + " template_DE_stats_filename,\n", + " template_DE_stats,\n", + " simulated_DE_summary_stats,\n", + " col_to_rank_genes,\n", + " local_dir,\n", + " 'gene',\n", + " params\n", + ")\n", + "\n", + "summary_gene_ranks.sort_values(by=\"Z score\", ascending=False).head()" + ] + }, + { + "cell_type": "code", + "execution_count": 14, + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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Gene IDAdj P-value (Real)Rank (Real)abs(logFC) (Real)logFC (Real)Median adj p-value (simulated)Rank (simulated)Mean abs(logFC) (simulated)Std deviation (simulated)Number of experiments (simulated)Z scoreGene Name
PA2195PA21950.0134045504.01.549834-1.5498340.7333403092.00.127540.0770982518.447771hcnC
PA4726PA47260.0000105549.04.530917-4.5309170.5547274636.50.248040.2429612517.627806cbrB
PA2260PA22600.0347415387.00.9536350.9536350.7417301713.00.089600.0507182517.036139NaN
PA3915PA39150.0009205535.02.065593-2.0655930.3914125308.00.288700.1092852516.259220moaB1
PA5168PA51680.0051375475.01.292737-1.2927370.7072603344.50.138700.0751712515.352146dctQ
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" + ], + "text/plain": [ + " Gene ID Adj P-value (Real) Rank (Real) abs(logFC) (Real) \\\n", + "PA2195 PA2195 0.013404 5504.0 1.549834 \n", + "PA4726 PA4726 0.000010 5549.0 4.530917 \n", + "PA2260 PA2260 0.034741 5387.0 0.953635 \n", + "PA3915 PA3915 0.000920 5535.0 2.065593 \n", + "PA5168 PA5168 0.005137 5475.0 1.292737 \n", + "\n", + " logFC (Real) Median adj p-value (simulated) Rank (simulated) \\\n", + "PA2195 -1.549834 0.733340 3092.0 \n", + "PA4726 -4.530917 0.554727 4636.5 \n", + "PA2260 0.953635 0.741730 1713.0 \n", + "PA3915 -2.065593 0.391412 5308.0 \n", + "PA5168 -1.292737 0.707260 3344.5 \n", + "\n", + " Mean abs(logFC) (simulated) Std deviation (simulated) \\\n", + "PA2195 0.12754 0.077098 \n", + "PA4726 0.24804 0.242961 \n", + "PA2260 0.08960 0.050718 \n", + "PA3915 0.28870 0.109285 \n", + "PA5168 0.13870 0.075171 \n", + "\n", + " Number of experiments (simulated) Z score Gene Name \n", + "PA2195 25 18.447771 hcnC \n", + "PA4726 25 17.627806 cbrB \n", + "PA2260 25 17.036139 NaN \n", + "PA3915 25 16.259220 moaB1 \n", + "PA5168 25 15.352146 dctQ " + ] + }, + "execution_count": 14, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Add gene name as column to summary dataframe\n", + "summary_gene_ranks = ranking.add_pseudomonas_gene_name_col(summary_gene_ranks, base_dir)\n", + "summary_gene_ranks.sort_values(by=\"Z score\", ascending=False).head()" + ] + }, + { + "cell_type": "code", + "execution_count": 15, + "metadata": {}, + "outputs": [ + { + "data": { + "text/plain": [ + "Gene ID False\n", + "Adj P-value (Real) False\n", + "Rank (Real) False\n", + "abs(logFC) (Real) False\n", + "logFC (Real) False\n", + "Median adj p-value (simulated) False\n", + "Rank (simulated) False\n", + "Mean abs(logFC) (simulated) False\n", + "Std deviation (simulated) False\n", + "Number of experiments (simulated) False\n", + "Z score False\n", + "Gene Name True\n", + "dtype: bool" + ] + }, + "execution_count": 15, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Check if there is an NaN values, there should not be\n", + "summary_gene_ranks.isna().any()" + ] + }, + { + "cell_type": "code", + "execution_count": 16, + "metadata": {}, + "outputs": [], + "source": [ + "# Create `gene_summary_filename`\n", + "summary_gene_ranks.to_csv(gene_summary_filename, sep='\\t')" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "## Compare gene ranking" + ] + }, + { + "cell_type": "code", + "execution_count": 17, + "metadata": { + "scrolled": false + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "r = 0.3743837960745028\n", + "p = 3.621704632637787e-184\n", + "ci_low = 0.3509873530823741\n", + "ci_high = 0.3988725360726553\n" + ] + }, + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/scipy/stats/stats.py:1713: FutureWarning: Using a non-tuple sequence for multidimensional indexing is deprecated; use `arr[tuple(seq)]` instead of `arr[seq]`. In the future this will be interpreted as an array index, `arr[np.array(seq)]`, which will result either in an error or a different result.\n", + " return np.add.reduce(sorted[indexer] * weights, axis=axis) / sumval\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/matplotlib/font_manager.py:1238: UserWarning: findfont: Font family ['Verdana'] not found. Falling back to DejaVu Sans.\n", + " (prop.get_family(), self.defaultFamily[fontext]))\n" + ] + }, + { + "data": { + "image/png": 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+ "text/plain": [ + "
" + ] + }, + "metadata": { + "needs_background": "light" + }, + "output_type": "display_data" + } + ], + "source": [ + "# Get generic genes identified by Crow et. al.\n", + "GAPE_filename = params['reference_gene_filename']\n", + "ref_gene_col = params['reference_gene_name_col']\n", + "ref_rank_col = params['reference_rank_col']\n", + "\n", + "figure_filename = f\"gene_ranking_{col_to_rank_genes}_pao1.svg\"\n", + "\n", + "corr, shared_ranking = ranking.compare_gene_ranking(\n", + " summary_gene_ranks,\n", + " GAPE_filename,\n", + " ref_gene_col,\n", + " ref_rank_col,\n", + " figure_filename\n", + ")" + ] + }, + { + "cell_type": "code", + "execution_count": 18, + "metadata": {}, + "outputs": [], + "source": [ + "# Get genes that are highly generic in both\n", + "generic_both = shared_ranking[(shared_ranking[\"Rank (simulated)\"]>4500) & (shared_ranking[\"prop DEGs\"]>3500)]\n", + "generic_both.to_csv(os.path.join(local_dir, \"SOPHIE_GAPE_generic.tsv\"), sep=\"\\t\")" + ] + }, + { + "cell_type": "code", + "execution_count": 19, + "metadata": {}, + "outputs": [], + "source": [ + "# Get genes that are highly generic by SOPHIE but not by GAPE\n", + "generic_SOPHIE_only = shared_ranking[(shared_ranking[\"Rank (simulated)\"]>4500) & (shared_ranking[\"prop DEGs\"]<2000)]\n", + "generic_SOPHIE_only.to_csv(os.path.join(local_dir, \"SOPHIE_generic_only.tsv\"), sep=\"\\t\")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "**Takeaway:**\n", + "\n", + "* X-axis: gene ranking using SOPHIE (trained on Pseudomonas compendium containing ~1K experiments)\n", + "* Y-axis: gene ranking using GAPE (curated set of 73 experiments)\n", + "\n", + "* Compared to the correlation plot comparing SOPHIE trained on the full pseudomonas compendium vs GAPE experiments [here](2_identify_generic_genes_pathways.ipynb), it looks like there is more noise in the above correlation plot. Looking up the experiment ids associated with GAPE [here](https://github.com/DartmouthStantonLab/GAPE/blob/main/Pa_GSEnum_unzip.rds) it looks like GAPE does contain a mix of PAO1, PA14 and clinical strains. So by subsetting out training compendium to only represent PAO1 patterns, which is adding more noise to the bottom left of the plot as expected (genes that GAPE finds generic are not found by SOPHIE due to our limited representation in our training compendium)" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### GSEA \n", + "**Goal:** To detect modest but coordinated changes in prespecified sets of related genes (i.e. those genes in the same pathway or share the same GO term).\n", + "\n", + "1. Ranks all genes based using DE association statistics. \n", + "2. An enrichment score (ES) is defined as the maximum distance from the middle of the ranked list. Thus, the enrichment score indicates whether the genes contained in a gene set are clustered towards the beginning or the end of the ranked list (indicating a correlation with change in expression). \n", + "3. Estimate the statistical significance of the ES by a phenotypic-based permutation test in order to produce a null distribution for the ES( i.e. scores based on permuted phenotype)" + ] + }, + { + "cell_type": "code", + "execution_count": 20, + "metadata": {}, + "outputs": [], + "source": [ + "# Create \"/GSEA_stats/\" subdirectory\n", + "os.makedirs(os.path.join(local_dir, \"GSA_stats\"), exist_ok=True)" + ] + }, + { + "cell_type": "code", + "execution_count": 21, + "metadata": {}, + "outputs": [], + "source": [ + "# Load pathway data\n", + "adage_kegg_DB_filename = params['pathway_DB_filename']" + ] + }, + { + "cell_type": "code", + "execution_count": 22, + "metadata": {}, + "outputs": [], + "source": [ + "# Need to format data into tab-delimited matrix\n", + "# with columns= KEGG pathway name, description, gene ids\n", + "# Each gene ids is tab separated\n", + "adage_kegg_DB_processed_filename = os.path.join(\n", + " base_dir,\n", + " dataset_name,\n", + " \"data\",\n", + " \"metadata\",\n", + " \"adage_kegg_DB_process_filename.gmt\"\n", + ")\n", + "stats.format_pseudomonas_pathway_DB(adage_kegg_DB_filename, local_dir, adage_kegg_DB_processed_filename)" + ] + }, + { + "cell_type": "code", + "execution_count": 23, + "metadata": { + "scrolled": false + }, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/rinterface/__init__.py:146: RRuntimeWarning: Loading required package: Rcpp\n", + "\n", + " warnings.warn(x, RRuntimeWarning)\n", + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/rpy2/robjects/pandas2ri.py:191: FutureWarning: from_items is deprecated. Please use DataFrame.from_dict(dict(items), ...) instead. DataFrame.from_dict(OrderedDict(items)) may be used to preserve the key order.\n", + " res = PandasDataFrame.from_items(items)\n" + ] + } + ], + "source": [ + "%%R -i base_dir -i template_DE_stats_filename -i adage_kegg_DB_processed_filename -i statistic -o template_enriched_pathways\n", + "\n", + "source(paste0(base_dir, '/generic_expression_patterns_modules/GSEA_analysis.R'))\n", + "\n", + "out_filename <- paste(local_dir, \n", + " \"GSA_stats/GSEA_stats_template_data_\",\n", + " project_id,\n", + " \"_real.txt\", \n", + " sep = \"\")\n", + "\n", + "template_enriched_pathways <- find_enriched_pathways(template_DE_stats_filename, adage_kegg_DB_processed_filename, statistic)\n", + "write.table(as.data.frame(template_enriched_pathways[1:7]), file = out_filename, row.names = F, sep = \"\\t\")" + ] + }, + { + "cell_type": "code", + "execution_count": 24, + "metadata": { + "scrolled": true + }, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "(169, 8)\n" + ] + }, + { + "data": { + "text/html": [ + "
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162KEGG-Module-M00360: Aminoacyl-tRNA biosynthesi...0.0001290.0009730.7143983.3764810.021None
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" + ], + "text/plain": [ + " pathway pval padj \\\n", + "168 KEGG-Module-M00178: Ribosome, bacteria 0.000113 0.000973 \n", + "91 KEGG-Pathway-pae00010: Glycolysis / Gluconeoge... 0.000121 0.000973 \n", + "90 KEGG-Pathway-pae00540: Lipopolysaccharide bios... 0.000132 0.000973 \n", + "145 KEGG-Module-M00009: Citrate cycle (TCA cycle, ... 0.000128 0.000973 \n", + "162 KEGG-Module-M00360: Aminoacyl-tRNA biosynthesi... 0.000129 0.000973 \n", + "\n", + " ES NES nMoreExtreme size leadingEdge \n", + "168 0.914364 6.154521 0.0 55 None \n", + "91 0.451513 2.576971 0.0 35 None \n", + "90 0.523175 2.373764 0.0 19 None \n", + "145 0.682962 3.288370 0.0 22 None \n", + "162 0.714398 3.376481 0.0 21 None " + ] + }, + "execution_count": 24, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "print(template_enriched_pathways.shape)\n", + "template_enriched_pathways[template_enriched_pathways['padj'] < 0.05].sort_values(by='padj').head()" + ] + }, + { + "cell_type": "code", + "execution_count": 25, + "metadata": {}, + "outputs": [], + "source": [ + "%%R -i project_id -i local_dir -i adage_kegg_DB_processed_filename -i num_runs -i statistic\n", + "\n", + "source(paste0(base_dir, '/generic_expression_patterns_modules/GSEA_analysis.R'))\n", + "\n", + "# New files created: \"/GSEA_stats/GSEA_stats_simulated_data__.txt\"\n", + "for (i in 0:(num_runs-1)) {\n", + " simulated_DE_stats_filename <- paste(local_dir, \n", + " \"DE_stats/DE_stats_simulated_data_\", \n", + " project_id,\n", + " \"_\", \n", + " i,\n", + " \".txt\",\n", + " sep = \"\")\n", + " \n", + " out_filename <- paste(local_dir, \n", + " \"GSA_stats/GSEA_stats_simulated_data_\",\n", + " project_id,\n", + " \"_\",\n", + " i,\n", + " \".txt\", \n", + " sep = \"\")\n", + " \n", + " enriched_pathways <- find_enriched_pathways(simulated_DE_stats_filename, adage_kegg_DB_processed_filename, statistic) \n", + " \n", + " # Remove column with leading edge since its causing parsing issues\n", + " write.table(as.data.frame(enriched_pathways[1:7]), file = out_filename, row.names = F, sep = \"\\t\")\n", + "}" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Rank pathways " + ] + }, + { + "cell_type": "code", + "execution_count": 26, + "metadata": {}, + "outputs": [], + "source": [ + "analysis_type = \"GSA\"\n", + "template_GSEA_stats_filename = os.path.join(\n", + " local_dir,\n", + " \"GSA_stats\",\n", + " f\"GSEA_stats_template_data_{project_id}_real.txt\" \n", + ")\n", + "template_GSEA_stats, simulated_GSEA_summary_stats = ranking.process_and_rank_genes_pathways(\n", + " template_GSEA_stats_filename,\n", + " local_dir,\n", + " num_runs,\n", + " project_id,\n", + " analysis_type,\n", + " col_to_rank_pathways,\n", + " \"GSEA\"\n", + ")" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "### Pathway summary table" + ] + }, + { + "cell_type": "code", + "execution_count": 27, + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "/home/alexandra/anaconda3/envs/generic_expression/lib/python3.7/site-packages/pandas/core/reshape/merge.py:544: UserWarning: merging between different levels can give an unintended result (1 levels on the left, 2 on the right)\n", + " warnings.warn(msg, UserWarning)\n" + ] + }, + { + "data": { + "text/html": [ + "
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Pathway IDAdj P-value (Real)Rank (Real)padj (Real)Median adj p-value (simulated)Rank (simulated)Mean padj (simulated)Std deviation (simulated)Number of experiments (simulated)Z score
pathway
KEGG-Module-M00178: Ribosome, bacteriaKEGG-Module-M00178: Ribosome, bacteria0.000973157.00.0009730.00129162.50.0012830.00016725-1.861053
KEGG-Pathway-pae00190: Oxidative phosphorylation - Pseudomonas aeruginosa PAO1KEGG-Pathway-pae00190: Oxidative phosphorylati...0.000973157.00.0009730.00129162.50.0012830.00016725-1.861053
KEGG-Pathway-pae00020: Citrate cycle (TCA cycle) - Pseudomonas aeruginosa PAO1KEGG-Pathway-pae00020: Citrate cycle (TCA cycl...0.000973157.00.0009730.00129162.50.0012830.00016725-1.861053
KEGG-Module-M00011: Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetateKEGG-Module-M00011: Citrate cycle, second carb...0.000973157.00.0009730.00129162.50.0013140.00023325-1.467433
KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth...0.000973157.00.0009730.00129162.50.0012830.00016725-1.861053
\n", + "
" + ], + "text/plain": [ + " Pathway ID \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria KEGG-Module-M00178: Ribosome, bacteria \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... KEGG-Pathway-pae00190: Oxidative phosphorylati... \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... KEGG-Pathway-pae00020: Citrate cycle (TCA cycl... \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... KEGG-Module-M00011: Citrate cycle, second carb... \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynth... \n", + "\n", + " Adj P-value (Real) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.000973 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.000973 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 0.000973 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 0.000973 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.000973 \n", + "\n", + " Rank (Real) padj (Real) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 157.0 0.000973 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 157.0 0.000973 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 157.0 0.000973 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 157.0 0.000973 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 157.0 0.000973 \n", + "\n", + " Median adj p-value (simulated) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.00129 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.00129 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 0.00129 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 0.00129 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.00129 \n", + "\n", + " Rank (simulated) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 162.5 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 162.5 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 162.5 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 162.5 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 162.5 \n", + "\n", + " Mean padj (simulated) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.001283 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.001283 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 0.001283 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 0.001314 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.001283 \n", + "\n", + " Std deviation (simulated) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 0.000167 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 0.000167 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 0.000167 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 0.000233 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 0.000167 \n", + "\n", + " Number of experiments (simulated) \\\n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria 25 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... 25 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... 25 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... 25 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... 25 \n", + "\n", + " Z score \n", + "pathway \n", + "KEGG-Module-M00178: Ribosome, bacteria -1.861053 \n", + "KEGG-Pathway-pae00190: Oxidative phosphorylatio... -1.861053 \n", + "KEGG-Pathway-pae00020: Citrate cycle (TCA cycle... -1.861053 \n", + "KEGG-Module-M00011: Citrate cycle, second carbo... -1.467433 \n", + "KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthe... -1.861053 " + ] + }, + "execution_count": 27, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Create intermediate file: \"/gene_summary_table_.tsv\"\n", + "summary_pathway_ranks = ranking.generate_summary_table(\n", + " template_GSEA_stats_filename,\n", + " template_GSEA_stats,\n", + " simulated_GSEA_summary_stats,\n", + " col_to_rank_pathways,\n", + " local_dir,\n", + " 'pathway',\n", + " params\n", + ")\n", + "\n", + "summary_pathway_ranks.sort_values(by='Rank (simulated)', ascending=False).head()" + ] + }, + { + "cell_type": "code", + "execution_count": 29, + "metadata": {}, + "outputs": [], + "source": [ + "# Create `pathway_summary_filename`\n", + "summary_pathway_ranks.to_csv(pathway_summary_filename, sep='\\t')" + ] + }, + { + "cell_type": "markdown", + "metadata": {}, + "source": [ + "**Quick check:**\n", + "\n", + "Looks like Ribosomes are found to be significantly differentiated in the template and across 25 simulated experiments. So this pathway looks to be generic, which is consistent with findings from [Crow. et. al.](https://www.pnas.org/content/116/13/6491.abstract), using Human data. This is also consistent with [paper](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679180/) which observed that Ribosome proteins have many different functions in *S. cerevisiae*, which might explain their variability across a wide range of contexts.\n", + "\n", + "* Need to think about why it might make sense that Ribosomes being generic in Humans would also imply that they are generic in P. aeruginosa." + ] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python [conda env:generic_expression] *", + "language": "python", + "name": "conda-env-generic_expression-py" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.7.9" + } + }, + "nbformat": 4, + "nbformat_minor": 4 +} diff --git a/pseudomonas_analysis/GAPE_proportions.txt b/pseudomonas_analysis/GAPE_proportions.txt new file mode 100644 index 00000000..fc3c63c5 --- /dev/null +++ b/pseudomonas_analysis/GAPE_proportions.txt @@ -0,0 +1,5901 @@ +ProbeID experiment_0 experiment_1 experiment_2 experiment_3 experiment_4 experiment_5 experiment_6 experiment_7 experiment_8 experiment_9 experiment_10 experiment_11 experiment_12 experiment_13 experiment_14 experiment_15 experiment_16 experiment_17 experiment_18 experiment_19 experiment_20 experiment_21 experiment_22 experiment_23 experiment_24 experiment_25 experiment_26 experiment_27 experiment_28 experiment_29 experiment_30 experiment_31 experiment_32 experiment_33 experiment_34 experiment_35 experiment_36 experiment_37 experiment_38 experiment_39 experiment_40 experiment_41 experiment_42 experiment_43 experiment_44 experiment_45 experiment_46 experiment_47 experiment_48 experiment_49 experiment_50 experiment_51 experiment_52 experiment_53 experiment_54 experiment_55 experiment_56 experiment_57 experiment_58 experiment_59 experiment_60 experiment_61 experiment_62 experiment_63 experiment_64 experiment_65 experiment_66 experiment_67 experiment_68 experiment_69 experiment_70 experiment_71 experiment_72 prop DEGs gene id +AFFX-Athal_GAPDH_at 0 0 0 0 0 0 0.0 0 0.0 1 1 0 0 0 1 1 0 0 0.0 0 0.0 1 0 0 0 0 1 0 0.0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0 0 0 0 0 0 0 0.0821917808219178 AFFX-Athal +AFFX-Athal_actin_at 0 0 0 0 0 0 0.0 0 0.0 0 0 0 0 0 1 1 0 0 0.0 0 1 0 0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0.0821917808219178 AFFX-Athal +AFFX-Athal_ubq_at 0 0 0 0 0 0.0 0 0.0 1 0.0 0 0 0 0 1 1 1 0 0 0.0 0 0.0 1 0 0 0 0 1 0 0.0 0 0 0 0 0 0 0 0 0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 1 0 0 0 0 0 0 0 0.0958904109589041 AFFX-Athal +AFFX-Bsubtilis_dapB_at 1 0 1 0 0 0.0 0 0.0 0 0.0 1 1 0 0 0 0 1 1 0 0.0 0 0.0 1 1 0 1 0 0 0 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 1 0.0 0 0.0 0 0 0 0 0 0 0 0 0 0.1506849315068493 AFFX-Bsubtilis +AFFX-Bsubtilis_lys_at 0 0 1 0 0 0.0 0 0.0 1 0.0 1 1 0 0 0 1 1 1 0 0.0 0 1 1 0 0.0 0 0 1 0 1.0 0 0 0 1 0 0 0 0 0 0 0.0 0 0 0 0 0 0.0 0 0 0 0 0 0 0 0 0 0 0.1643835616438356 AFFX-Bsubtilis +AFFX-Bsubtilis_pheB_at 1 0 1 0 0 0.0 0 0.0 0 0.0 1 1 0 0 0 0 1 1 0 0.0 0 1.0 1 1 0 0.0 1 1 0 0 1.0 0 0 0 0 0 0 0 0 0 0.0 0 0.0 0 0 0 0 1 0.0 0 0.0 0 0 0 0 0 0 0 0 0 0.1780821917808219 AFFX-Bsubtilis +AFFX-Bsubtilis_thrC_at 1 0 1 0 0 0.0 0 0.0 0 0.0 0 1 0 0 0 0 1 1 0 0.0 0 1.0 1 1 0 1 1 0 0 1.0 0 0 0 0 0 0 0 0 0 0.0 1.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 0 0 0 0 0 0 0 0.1780821917808219 AFFX-Bsubtilis +AFFX-Bsubtilis_trpD_at 0 0 1 0 0 0 0 0.0 1 1 0 0 0 1 1 0 0 0.0 0 1.0 1 0 0 0 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 1 0 0 0 0 0 0 0 0.136986301369863 AFFX-Bsubtilis +AFFX-YEL002C_WPB1_at 0 0 0 0 0 0 0 0 1 0 0 0 1 1 1 0 0.0 0 1 0 0 0 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 1 0 0 0 0 0 0 0 0.1095890410958904 AFFX-YEL002C +AFFX-YEL018W_at 0 0 0 0 0 0 0 1 1 0 0 0 1 1 0 0 0.0 0 1.0 1 0 0 0 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0 0 0 1 0 0 0 0.1232876712328767 AFFX-YEL018W +AFFX-YEL024W_RIP1_at 0 0 0 0 0 0 0.0 1 0.0 1 1 0 0 0 1 1 0 0 0.0 0 1 0 0 0.0 0 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 0 0 0 0.0 0 0 0 0 0 0 1 0 0 0 0.1232876712328767 AFFX-YEL024W +AFFX-YER022W_SRB4_at 0 0 0 0 0 0 0 0 1 0 0 0 1 1 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 1 0 0 0 1 0 0 0 0.0958904109589041 AFFX-YER022W +AFFX-YER148W_SPT15_at 0 0 0 0 0 0.0 0 0 0.0 1 1 0 0 0 1 1 1 0 0.0 0 0.0 1 0 0 0.0 0 0 1 1 1.0 0 0 0 0 0 0 0 0 0 0 1.0 0 0 0 0 0 0.0 0 0.0 0 0 0 0 0 1 0 0 0 0.1506849315068493 AFFX-YER148W +AFFX-YFL039C_ACT1_at 0 0 0 0 0 0.0 0 0.0 0 0.0 1 0 0 0 0 1 1 0 0 0.0 0 1.0 1 0 0 0 0 1 0 0.0 0 0 0 0 0 0 0 0 0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 1 0 0 0 0 0 0 0 0.0958904109589041 AFFX-YFL039C +PA0001_dnaA_at 1 0 1 0 0 1.0 0 0.0 1 1.0 1 1 0 0 0 1 1 1 1 0.0 1.0 1 0.0 1 0 0 0.0 0 1 1 0 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 1 1.0 0 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3150684931506849 PA0001 +PA0002_dnaN_at 1 0 1 0 0 0.0 0 0.0 1 1.0 0 1 0 0 1 0 1 1 1 0.0 1.0 1 0.0 1 0 0 0.0 0 0 1 0 0.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2191780821917808 PA0002 +PA0003_recF_at 1 0 1 0 0 1.0 0 0.0 1 1.0 0 1 1 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 1 0.0 0 0 0 1 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3013698630136986 PA0003 +PA0004_gyrB_at 0 0 1 0 0 0.0 0 0.0 0 0.0 0 1 0 0 0 0 1 1 1 0.0 1.0 1 0.0 1 0 0 0.0 0 1 1 0 0.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 1 1 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.2328767123287671 PA0004 +PA0005_at 0 0 1 0 0 0.0 0 0.0 0 1.0 0 1 0 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 1 0 1 0 0.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.2191780821917808 PA0005 +PA0006_at 1 0 0 0 0 0.0 0 0.0 1 1.0 0 0 0 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 1 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 0 0 0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1780821917808219 PA0006 +PA0007_at 0 0 1 0 0 0.0 0 0.0 1 0.0 0 1 0 0 1 1 1 1 1 1.0 1.0 0 1.0 1 0 0 0 0 1 0 1.0 1 0 0 0 1 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3013698630136986 PA0007 +PA0008_glyS_at 1 0 1 0 0 0.0 0 0.0 0 0.0 0 1 1 0 1 0 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 1 1 0 0.0 0 0 0 1 1 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 1 0 0 1.0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3013698630136986 PA0008 +PA0009_glyQ_at 1 0 0 1 0 1.0 1 0.0 1 1.0 0 1 1 0 0 1 0 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 1 0 0 0.0 0 0 0 1 1 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 1 0 0 1.0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3287671232876712 PA0009 +PA0010_tag_at 0 0 0 0 0 0.0 0 0.0 0 0.0 0 1 0 0 0 1 0 1 0 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 0 0 0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0958904109589041 PA0010 +PA0011_at 0 0 0 0 0 0.0 0 0.0 0 1.0 0 1 0 0 0 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 1 0 0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1506849315068493 PA0011 +PA0012_at 1 0 0 0 0 0.0 0 0.0 0 1.0 0 0 0 0 0 1 1 1 1 0.0 1.0 0 0.0 0 0 0 0.0 0 0 1 1 0.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 1 0 0 0.0 0 1 0 0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1643835616438356 PA0012 +PA0013_at 0 0 0 0 0 0.0 0 0.0 0 1.0 0 0 1 0 0 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 1 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.1643835616438356 PA0013 +PA0014_at 0 0 0 0 0 0.0 0 0.0 0 0.0 1 0 0 0 0 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 0 0 0 0.0 0.0 0.0 0.0 0.0 0.1232876712328767 PA0014 +PA0015_at 0 0 0 0 0 0.0 0 0.0 0 1.0 1 1 1 0 0 1 1 1 0 0.0 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0.0 1 0 0 0.0 0 1 1 0 0.0 0 1 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 0.0 1 0 0 1.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3150684931506849 PA1985 +PA1986_pqqB_at 0 0 1 1 0 1.0 0 0.0 1 1.0 0 1 1 0 1 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 1 1.0 1 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3561643835616438 PA1986 +PA1987_pqqC_at 0 0 1 1 0 1.0 0 0.0 1 0.0 1 1 1 0 1 1 0 1 0 0.0 1.0 0 0.0 1 0 0 0.0 0 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 0 0 0 0.0 1.0 1.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3287671232876712 PA1987 +PA1988_pqqD_at 0 0 1 1 0 1.0 0 0.0 1 0.0 0 1 1 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 1 0 0 1.0 0 0 0 0 0.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3150684931506849 PA1988 +PA1989_pqqE_at 1 0 1 1 0 1.0 0 0.0 1 0.0 0 1 1 0 1 1 0 1 1 0.0 0.0 0 0.0 1 0 0 0.0 0 0 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 0 0 0 0.0 1.0 1.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3013698630136986 PA1989 +PA1990_at 0 0 1 0 0 1.0 0 0.0 0 0.0 1 0 0 0 0 1 1 1 0 0.0 0.0 0 0.0 1 0 0 0.0 0 0 1 1 0.0 0 0 0 1 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 1 0 0 1.0 0 0 0 0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.2465753424657534 PA1990 +PA1991_at 0 0 0 0 0 1.0 0 0.0 0 0.0 0 0 0 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 1 1 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 0.1917808219178082 PA1991 +PA1992_at 0 0 1 0 0 0.0 0 0.0 0 0.0 0 0 0 0 0 1 0 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 0 0.0 0 1 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.1780821917808219 PA1992 +PA1993_at 0 0 0 0 0 0.0 0 0.0 1 0.0 0 1 0 0 0 1 0 1 0 0.0 1.0 0 0.0 1 0 0 0 0 1 1 0.0 0 1 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 1 0 0 0.0 0 0 0 0 0.0 0.0 0.0 1.0 0.0 0.0 0.1643835616438356 PA1993 +PA1994_at 0 0 0 1 0 0.0 0 0.0 1 0.0 0 0 0 0 0 1 0 1 0 0.0 0.0 0 0.0 0 0 0 1.0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 0 0 0 0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.1232876712328767 PA1994 +PA1995_i_at 1 0 0 0 0 0.0 0 0.0 0 0.0 0 1 0 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.1780821917808219 PA1995 +PA1996_ppiC1_at 0 0 0 0 0 0.0 0 0.0 0 1.0 0 0 1 0 0 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 0 0.0 0 0 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 0 0 0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.1506849315068493 PA1996 +PA1997_at 0 0 0 0 0 0.0 0 0.0 1 0.0 0 1 0 0 0 1 0 1 1 0.0 1.0 0 0.0 1 0 0 0.0 1 0 1 1 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.2191780821917808 PA1997 +PA1998_at 1 0 0 0 0 0.0 0 0.0 1 0.0 0 1 0 0 1 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0.0 0 0 1 1 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 1 0 0 0.0 0 0 0 0 0.0 0.0 0.0 1.0 0.0 1.0 0.2328767123287671 PA1998 +PA1999_at 1 0 1 0 0 1.0 1 0.0 1 1.0 1 1 1 0 0 1 1 1 1 1.0 1.0 0 0.0 1 0 0 0.0 1 1 1 1 1.0 1 1 0 1 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 0 0 0.0 1 0.0 0 0 1.0 1 0 0 1.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.4383561643835616 PA1999 +PA2000_at 0 0 1 0 0 1.0 1 0.0 1 1.0 1 1 1 0 0 0 1 1 1 1.0 1.0 0 0.0 1 0 0 0.0 1 0 1 1 1.0 0 1 0 1 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 1 0.0 0 0 1.0 1 0 0 0.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3835616438356164 PA2000 +PA2001_atoB_at 0 0 1 0 0 1.0 0 0.0 1 1.0 1 1 0 0 0 0 1 1 1 1.0 1.0 0 0.0 1 0 0 0.0 1 0 1 1 1.0 1 1 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 1 1.0 1 0 0 1.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3561643835616438 PA2001 +PA2002_at 0 0 1 0 0 0.0 0 0.0 1 0.0 0 1 0 0 0 1 0 1 1 1.0 1.0 0 0.0 1 0 0 0.0 0 1 1 1 1.0 0 1 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 1.0 1 0 0 0.0 0 0 0 0 1.0 1.0 1.0 0.0 0.0 1.0 0.0 0.0 1.0 0.2876712328767123 PA2002 +PA2003_bdhA_at 1 0 1 0 0 0.0 0 0.0 1 1.0 0 1 0 0 0 0 0 1 1 0.0 1.0 0 0.0 1 0 0 0.0 1 1 1 1 1.0 0 1 0 1 1 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 0 0 0 0 1.0 0.0 1.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3287671232876712 PA2003 +PA2004_at 0 0 1 0 0 0.0 0 0.0 0 1.0 0 1 0 0 1 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0.0 1 1 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 1.0 0 0 0 0 1.0 0.0 1.0 0.0 0.0 1.0 0.0 1.0 0.2465753424657534 PA2004 +PA2005_at 0 0 0 0 0 0.0 0 0.0 0 0.0 0 0 0 0 0 1 0 1 0 0.0 1.0 0 0.0 1 0 0 0 0 1 1 0.0 0 0 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 0.0 0 0 0 0.0 0 0 0 0 0.0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.1232876712328767 PA2005 +PA2006_at 0 0 1 0 0 0.0 0 0.0 1 0.0 1 1 0 0 0 1 1 1 1 0.0 1.0 0 1.0 1 0 0 1 0 1 0 0.0 0 1 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 1 1.0 1 0 0 0.0 0 0 0 0 1.0 1.0 1.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3150684931506849 PA2006 +PA2007_maiA_i_at 1 0 1 0 0 0.0 1 0.0 1 1.0 1 1 1 0 0 1 1 1 1 0.0 1.0 0 1.0 1 0 0 0.0 1 1 1 1 1.0 0 1 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 1.0 1 0 0 1.0 0 1 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3972602739726027 PA2007 +PA2008_fahA_at 1 0 1 0 0 1.0 1 0.0 1 1.0 0 1 0 0 0 1 1 1 1 0.0 1.0 0 1.0 1 0 0 0.0 1 0 1 1 1.0 0 1 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 1 0 0 1.0 1 1 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3972602739726027 PA2008 +PA2009_hmgA_at 1 0 1 1 0 1.0 1 0.0 1 1.0 1 1 1 0 0 1 1 1 1 0.0 1.0 0 1.0 1 0 0 0.0 1 1 1 1 1.0 0 1 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 1 0 0 1.0 1 1 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.4520547945205479 PA2009 +PA2010_at 0 0 0 0 0 0.0 0 0.0 0 0.0 0 0 0 0 0 1 0 1 1 0.0 1.0 0 0.0 1 0 0 1 0 1 1 0.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 1 1.0 1 0 0 0.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.1780821917808219 PA2010 +PA2011_at 0 0 1 0 0 0.0 0 0.0 1 1.0 0 1 1 0 0 1 1 1 0 0.0 1.0 0 0.0 1 0 0 0.0 1 1 1 1 1.0 1 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 1 0.0 0 0 1.0 1 0 0 0.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3013698630136986 PA2011 +PA2012_at 1 0 1 0 0 1.0 0 0.0 1 1.0 1 1 1 0 0 0 1 1 0 0.0 1.0 0 1.0 1 0 0 1.0 1 0 1 1 1.0 1 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 1.0 1 0 0 0.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3424657534246575 PA2012 +PA2013_at 1 0 1 0 0 1.0 0 0.0 1 1.0 0 1 1 0 0 1 1 1 0 1.0 1.0 0 0.0 1 0 0 1.0 1 0 1 1 1.0 1 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 1 0.0 0 0 1.0 1 0 0 1.0 0 0 0 0 0.0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3561643835616438 PA2013 +PA2014_at 1 0 1 0 0 1.0 0 0.0 1 1.0 0 1 1 0 0 1 1 1 0 1.0 1.0 0 0.0 1 0 0 1.0 1 0 1 1 1.0 1 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 1 0.0 0 0 1.0 1 0 0 0.0 0 0 0 0 0.0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3561643835616438 PA2014 +PA2015_at 1 0 1 1 0 0.0 1 0.0 1 1.0 0 1 1 0 0 1 1 0 1 1.0 1.0 0 0.0 1 0 0 1.0 1 0 1 1 1.0 1 1 0 0 0 0 0 0 0 1.0 0.0 0 0.0 0 0 0 1 0 0.0 1 0.0 0 1 0.0 0 0 0 1.0 1 0 0 0 1.0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 1.0 0.4246575342465753 PA2015 +PA2016_at 1 0 1 1 0 0.0 1 0.0 1 1.0 0 1 1 0 0 1 1 1 1 1.0 1.0 0 0.0 1 0 0 0.0 1 0 1 0 1.0 0 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 1 0.0 0 1 1.0 0 0 0 0.0 0 0 0 0 1.0 1.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0 0.3424657534246575 PA2016 +PA2017_at 0 0 0 0 0 0.0 0 0.0 1 0.0 0 1 0 0 1 0 0 1 0 0.0 1.0 0 0.0 1 0 0 0.0 1 0 1 1 1.0 1 0 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 1 1.0 0 0 0 0.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 0.0 0.2328767123287671 PA2017 +PA2018_at 0 0 1 0 0 0.0 0 0.0 1 1.0 1 0 1 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0 1 1 1 0.0 0 1 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 1 0 1 0 0.0 0 0.0 0 0 1.0 1 0 0 1.0 0 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3150684931506849 PA2018 +PA2019_at 0 0 1 0 0 0.0 0 0.0 1 1.0 1 1 1 0 0 1 1 1 1 0.0 1.0 0 0.0 1 0 0 0 1 1 1 0.0 0 1 0 0 0 0 0 0 0 0.0 0.0 0 0.0 0 1 0 1 0 0.0 0 0.0 0 1 1.0 1 0 0 1.0 0 1 0 0 0.0 0.0 0.0 1.0 0.0 1.0 0.3424657534246575 PA2019 +PA2020_at 0 0 1 0 0 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1.0 1 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3561643835616438 PA4237 +PA4238_rpoA_at 1 0 1 1 0 0.0 1 0.0 0 1.0 0 1 0 0 1 1 1 0 1 0.0 1.0 0 0.0 1 0 0 1.0 0 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3561643835616438 PA4238 +PA4239_rpsD_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 1 1 0 1 0.0 1.0 1 0.0 1 0 0 1.0 0 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3972602739726027 PA4239 +PA4240_rpsK_at 1 0 1 1 0 1.0 1 0.0 0 1.0 0 1 0 0 1 1 1 0 1 0.0 1.0 1 0.0 1 0 0 0.0 0 1 1 1 1.0 1 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3835616438356164 PA4240 +PA4241_rpsM_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 0 1 0 1 0.0 1.0 0 0.0 1 0 0 1.0 0 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 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0.0 1.0 0.0 0.0 1.0 0.3698630136986301 PA4245 +PA4246_rpsE_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 1 1 0 1 0.0 1.0 0 0.0 1 0 0 1.0 0 1 1 1 1.0 1 1 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.410958904109589 PA4246 +PA4247_rplR_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 1 1 0 1 0.0 0.0 0 0.0 1 0 0 1.0 0 1 1 1 1.0 0 1 0 1 1 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 1 1.0 0 0 0 1.0 1 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.410958904109589 PA4247 +PA4248_rplF_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 0 1 0 1 0.0 1.0 0 0.0 0 0 0 1.0 0 1 1 1 1.0 1 0 0 1 1 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 1 1.0 0 0 0 1.0 1 0 0 0 1.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3972602739726027 PA4248 +PA4249_rpsH_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 0 1 0 1 0.0 1.0 0 0.0 0 0 0 1.0 0 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 0 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3287671232876712 PA4249 +PA4250_rpsN_at 1 0 1 1 0 0.0 1 0.0 1 1.0 1 1 0 0 1 0 1 0 0 0.0 1.0 1 0.0 0 0 0 1.0 1 0 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3424657534246575 PA4250 +PA4251_rplE_at 1 0 1 1 0 0.0 1 0.0 0 1.0 0 1 0 0 1 1 1 1 0 0.0 1.0 0 0.0 0 0 0 1.0 1 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3424657534246575 PA4251 +PA4252_rplX_at 1 0 1 1 0 1.0 1 0.0 0 1.0 0 1 0 0 1 1 1 0 1 0.0 1.0 1 0.0 1 0 0 1.0 1 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3835616438356164 PA4252 +PA4253_rplN_at 1 0 1 1 0 1.0 1 0.0 1 1.0 0 1 0 0 1 1 1 0 0 0.0 1.0 1 0.0 1 0 0 1.0 1 1 1 1 1.0 0 0 0 1 0 0 0 0 0 0.0 0.0 0 0.0 0 0 0 1 0 0.0 0 0.0 0 0 1.0 0 0 0 1.0 1 0 0 0 0.0 1.0 0.0 0.0 0.0 1.0 0.0 0.0 1.0 0.3835616438356164 PA4253 +PA4254_rpsQ_at 1 0 1 1 0 0.0 1 0.0 1 1.0 0 1 0 0 1 0 1 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b/pseudomonas_analysis/generic_gene_summary_E-GEOD-33245_pao1.tsv @@ -0,0 +1,5550 @@ + Gene ID Adj P-value (Real) Rank (Real) abs(logFC) (Real) logFC (Real) Median adj p-value (simulated) Rank (simulated) Mean abs(logFC) (simulated) Std deviation (simulated) Number of experiments (simulated) Z score Gene Name +PA4726 PA4726 1.03210514995367e-05 5549.0 4.5309172961 -4.5309172961 0.554726815753945 4636.5 0.24803999999999973 0.24296145613382134 25 17.627805513896096 cbrB +PA1985 PA1985 0.0009256950258211481 5548.0 2.9733086354 2.9733086354 0.266349700958082 5549.0 0.7948599999999999 0.32328539764940406 25 6.738469016044084 pqqA +PA4131 PA4131 0.000347854211164523 5547.0 2.8816898638499997 -2.8816898638499997 0.535184211406048 5037.0 0.2657599999999998 0.1869797292934893 25 13.990446310594201 +PA4739 PA4739 0.000222976451073916 5546.0 2.7845411844 2.7845411844 0.509999366996707 5343.0 0.3412199999999999 0.2907412968029597 25 8.40376379711851 +PA1216 PA1216 0.000222976451073916 5545.0 2.60059401205 2.60059401205 0.407491151386434 5540.0 0.59586 0.24885213648537033 25 8.05592445523511 +PA1041 PA1041 0.000432338722001073 5544.0 2.5964791294 2.5964791294 0.359765789899418 5522.0 0.4454800000000001 0.16537378621373647 25 13.006892922073831 +PA4133 PA4133 0.00183726115211415 5543.0 2.59111779985 -2.59111779985 0.7600640125596569 5089.5 0.2237000000000001 0.19126367053538076 25 12.377770400532311 +PA3874 PA3874 0.000347854211164523 5542.0 2.5417589228999997 -2.5417589228999997 0.513789619753908 5383.0 0.30570000000000025 0.20973564710527037 25 10.661320351412073 narH +PA1988 PA1988 0.000347854211164523 5541.0 2.4499896907 2.4499896907 0.421716289475775 5510.0 0.4785400000000001 0.21260786086125727 25 9.272703665395138 pqqD +PA4738 PA4738 0.000478625409052826 5540.0 2.4246339388 2.4246339388 0.6458401134788722 5213.0 0.32360000000000044 0.26280014586500255 25 7.994797460574001 +PA1249 PA1249 0.000432338722001073 5539.0 2.40386664145 2.40386664145 0.34893666975285903 5545.0 0.6077799999999999 0.2448554879924076 25 7.335292568593327 aprA +PA2321 PA2321 0.000347854211164523 5538.0 2.24754751555 2.24754751555 0.42979859537313697 5261.0 0.29646000000000006 0.18539624906309893 25 10.52387804720879 +PA1123 PA1123 0.00257764216558392 5537.0 2.175899953 -2.175899953 0.587283813750561 5258.5 0.2849999999999997 0.20897682287756195 25 9.048371618262497 +PA4132 PA4132 0.0025177546952995303 5536.0 2.0867552607 -2.0867552607 0.7193513756077421 2510.5 0.1656599999999994 0.15867181276668768 25 12.107350557120025 +PA3915 PA3915 0.0009202912093884741 5535.0 2.0655932795500003 -2.0655932795500003 0.39141171163835703 5308.0 0.2887000000000002 0.10928527271930655 25 16.259219886963695 moaB1 +PA3875 PA3875 0.0023526329946137 5534.0 2.04260576145 -2.04260576145 0.477380260563382 5189.0 0.2665199999999998 0.17397374562463877 25 10.208929830608099 narG +PA4587 PA4587 0.000646342619969043 5533.0 1.9887072274000002 -1.9887072274000002 0.615305163023579 5302.0 0.24080000000000026 0.1701613817331462 25 10.272055913022244 ccpR +PA3873 PA3873 0.0011988028400653 5532.0 1.9539064102500001 -1.9539064102500001 0.42576323041245095 5419.0 0.3428999999999999 0.18190067115507527 25 8.85651713113567 narJ +PA1217 PA1217 0.00103855725901672 5531.0 1.9417529511000002 1.9417529511000002 0.46774737879232897 5340.0 0.2853600000000001 0.10901992554880348 25 15.193488188161577 +PA5167 PA5167 0.000599674990047699 5530.0 1.9254638203499999 -1.9254638203499999 0.691146664095048 4288.0 0.16601999999999997 0.11571061965092079 25 15.20555179514155 dctP +PA3872 PA3872 0.00110680793975753 5529.0 1.8917367071000002 -1.8917367071000002 0.38849616917415003 5436.0 0.35498000000000013 0.16058665106415276 25 9.569641666455086 narI +PA3334 PA3334 0.00513690711208909 5528.0 1.8607900447499999 1.8607900447499999 0.477380260563382 5467.0 0.37583999999999973 0.2279230370834269 25 6.515138020938456 +PA0572 PA0572 0.00110680793975753 5527.0 1.82033437375 1.82033437375 0.7284984532058941 2227.5 0.13934 0.11633551693270644 25 14.449537149711217 +PA0997 PA0997 0.00159323424379569 5526.0 1.81312710055 -1.81312710055 0.7265017683019341 4644.0 0.1832400000000003 0.13320380062145362 25 12.236040510449913 pqsB +PA2747 PA2747 0.00159323424379569 5525.0 1.77665758435 1.77665758435 0.5343832051175779 5294.0 0.30594000000000027 0.16461092511333095 25 8.934507739006044 +PA1555 PA1555 0.00110680793975753 5524.0 1.7666526274 -1.7666526274 0.7397104386978329 4552.5 0.19239999999999988 0.14403580284082113 25 10.929592478751692 ccoP2 +PA1173 PA1173 0.00110680793975753 5523.0 1.7650700153499999 1.7650700153499999 0.358906079379377 5532.0 0.49567999999999995 0.1693583405091106 25 7.495290822607661 napB +PA3452 PA3452 0.0009256950258211481 5522.0 1.7637430311000002 1.7637430311000002 0.5192911820230529 4893.0 0.25648000000000004 0.19587551744241397 25 7.695004719224928 mqoA +PA3038 PA3038 0.00110680793975753 5521.0 1.7496694505000001 -1.7496694505000001 0.579580812510079 5272.0 0.3183800000000001 0.1932697963124776 25 7.405655088423122 opdQ +PA1987 PA1987 0.00103855725901672 5520.0 1.7395245877 1.7395245877 0.35829084915265397 5426.0 0.37311999999999984 0.18397289655453802 25 7.427205927015097 pqqC +PA1556 PA1556 0.00110680793975753 5519.0 1.7122684732 -1.7122684732 0.7764733088851591 4507.5 0.19960000000000014 0.14133419319707016 25 10.702777855679988 ccoO2 +PA0996 PA0996 0.0025177546952995303 5518.0 1.7019719281 -1.7019719281 0.6089447456891479 4581.0 0.21489999999999998 0.16907413314874645 25 8.79538401531663 pqsA +PA3479 PA3479 0.00159323424379569 5517.0 1.7001970125 1.7001970125 0.4809390501325779 5535.0 0.50192 0.27400272504727635 25 4.3732302746012826 rhlA +PA4619 PA4619 0.00110680793975753 5516.0 1.69085341375 1.69085341375 0.599929239006224 4568.5 0.20313999999999965 0.17755976223983463 25 8.378663020175184 +PA0587 PA0587 0.0011264860443986802 5515.0 1.6908131322 1.6908131322 0.35829084915265397 5533.0 0.4716600000000002 0.16811217237309123 25 7.252021760175308 +PA2381 PA2381 0.0166232978960079 5514.0 1.638117522 -1.638117522 0.6072384262084699 5250.0 0.29499999999999965 0.24023850995763907 25 5.590766951713238 +PA0999 PA0999 0.00162717545183142 5513.0 1.63031330815 -1.63031330815 0.715840840567284 3783.0 0.1644600000000002 0.12174913757394754 25 12.03994818657073 pqsD +PA4620 PA4620 0.00110680793975753 5512.0 1.6113105062 1.6113105062 0.660042837237559 2760.0 0.1782600000000002 0.17419063551178662 25 8.226908995363488 +PA0588 PA0588 0.0040237724851552 5511.0 1.6024164221500001 1.6024164221500001 0.38037624022384703 5528.0 0.4909400000000004 0.2298106702628639 25 4.836487448031294 +PA2367 PA2367 0.00183726115211415 5510.0 1.59829511165 1.59829511165 0.40811283124466097 5491.0 0.38187999999999994 0.11709373737879132 25 10.388387448211418 hcp3 +PA2322 PA2322 0.0054583913758837 5509.0 1.59561384425 1.59561384425 0.611986408496905 4458.5 0.17921999999999982 0.12565520615292225 25 11.272066535199908 +PA0998 PA0998 0.00941463958485225 5508.0 1.5658060066 -1.5658060066 0.719841161592098 4749.0 0.1885599999999998 0.1294591570084299 25 10.638459560727087 pqsC +PA2664 PA2664 0.0054583913758837 5507.0 1.56129481595 1.56129481595 0.47424139336848403 5027.0 0.33270000000000016 0.2760720392095749 25 4.450268920632469 fhp +PA1001 PA1001 0.0038052738747829796 5506.0 1.55902684695 -1.55902684695 0.7352092655988149 4081.5 0.1812399999999997 0.13666139115834178 25 10.081756341508605 phnA +PA4134 PA4134 0.00181669615134485 5505.0 1.5582299888 -1.5582299888 0.7293373462351189 3612.0 0.18727999999999984 0.15493177799706995 25 8.848733336203805 +PA2195 PA2195 0.0134039813203279 5504.0 1.54983384255 -1.54983384255 0.7333402437632801 3092.0 0.12754000000000015 0.07709841113797329 25 18.447771122088366 hcnC +PA4607 PA4607 0.00257764216558392 5503.0 1.5118091336000001 1.5118091336000001 0.372184977296017 5516.0 0.4464800000000008 0.24468634173842477 25 4.353856149187355 +PA3790 PA3790 0.0448081734502191 5502.0 1.5112542463499998 -1.5112542463499998 0.748589611629593 4382.0 0.1606999999999999 0.11117394403965963 25 12.148118500394391 oprC +PA2679 PA2679 0.00584898285503005 5501.0 1.50944844685 1.50944844685 0.3647405707759929 5214.0 0.3227000000000001 0.16576200308474412 25 7.159351508579966 +PA2939 PA2939 0.00521323934476602 5500.0 1.50204274655 1.50204274655 0.505715022183909 5413.0 0.2807800000000001 0.13210626089124844 25 9.244548580141549 +PA0511 PA0511 0.001667126905862 5499.0 1.500236451 -1.500236451 0.505838694726331 4970.0 0.26497999999999977 0.25731010311813757 25 4.800652737808988 nirJ +PA0887 PA0887 0.00159323424379569 5498.0 1.4893087050999998 -1.4893087050999998 0.37648968428940105 5466.0 0.39249999999999957 0.24420683685488132 25 4.491310395833731 acsA +PA4130 PA4130 0.00348247781646228 5497.0 1.4754304308500001 -1.4754304308500001 0.736289580878041 4007.5 0.17279999999999962 0.18482598798148875 25 7.047874842040425 +PA2366 PA2366 0.00296260619229317 5496.0 1.4690349958500002 1.4690349958500002 0.5379053073236201 5385.0 0.32456 0.1698512412867999 25 6.738102042583917 hsiC3 +PA5446 PA5446 0.0023526329946137 5495.0 1.4641881136500001 1.4641881136500001 0.684029425087861 2603.5 0.1824600000000004 0.24179713087627794 25 5.300840870216242 +PA4500 PA4500 0.00272677635962165 5494.0 1.45460147885 -1.45460147885 0.6583052775960649 5134.0 0.2659600000000002 0.19009465405423667 25 6.25289272212181 dppA3 +PA3329 PA3329 0.0023526329946137 5493.0 1.4462760433500002 1.4462760433500002 0.5256667381808731 5406.0 0.3409200000000003 0.19481576125491806 25 5.67385326643891 +PA3183 PA3183 0.0050413143540997 5492.0 1.43574913815 1.43574913815 0.5967888975468281 5208.0 0.28073999999999977 0.21892174781566726 25 5.275899492281239 zwf +PA3877 PA3877 0.0128471265842686 5491.0 1.4137201751 -1.4137201751 0.444964871778219 5358.0 0.28486000000000056 0.11915890301050323 25 9.473569717241324 narK1 +PA0447 PA0447 0.00183726115211415 5490.0 1.41193193985 1.41193193985 0.5887436813479461 5052.0 0.2256799999999997 0.12973923205157833 25 9.143355645718648 gcdH +PA4496 PA4496 0.0025177546952995303 5489.0 1.40617431325 -1.40617431325 0.6699720951485749 4519.0 0.17246000000000022 0.09911766156106293 25 12.44696751133451 dppA1 +PA4129 PA4129 0.00265510264515629 5488.0 1.3825594637 -1.3825594637 0.712729120023638 3176.0 0.1782800000000006 0.16140361416853896 25 7.461291805042736 +PA1073 PA1073 0.00244145864111298 5487.0 1.3810457602000001 -1.3810457602000001 0.7441802488204721 3182.0 0.14831999999999973 0.14633607723319605 25 8.423936075828871 braD +PA0514 PA0514 0.00244145864111298 5486.0 1.3805947069 -1.3805947069 0.508707142513939 4871.5 0.2554400000000001 0.21575344338696692 25 5.215002315777489 nirL +PA3330 PA3330 0.0188055788585082 5485.0 1.36482541675 1.36482541675 0.457310670704513 5412.0 0.34735999999999995 0.17149590131156708 25 5.932884745166641 +PA3331 PA3331 0.00506779587980939 5484.0 1.3582294863 1.3582294863 0.477380260563382 5457.0 0.34643999999999997 0.1831369774240036 25 5.52476894907727 +PA3392 PA3392 0.00253404313782304 5483.0 1.3460936044999998 -1.3460936044999998 0.561874835386938 4573.0 0.2673000000000001 0.29046069728392965 25 3.714077720626908 nosZ +PA1989 PA1989 0.00505007269415247 5482.0 1.33178103515 1.33178103515 0.375745295937564 5120.5 0.2718200000000002 0.11520252818406364 25 9.200848730129065 pqqE +PA4501 PA4501 0.00475163735251706 5481.0 1.3125462299 -1.3125462299 0.679565144148437 4694.0 0.1951200000000001 0.13765213401905577 25 8.117754496601627 opdD +PA1984 PA1984 0.00252000788635419 5480.0 1.31177458959999 -1.31177458959999 0.622453801844744 4657.5 0.20733999999999975 0.14457918245722634 25 7.638959986004461 exaC +PA3333 PA3333 0.00896476053848933 5479.0 1.31119730115 1.31119730115 0.477380260563382 5359.0 0.2978200000000003 0.15400966419892825 25 6.579959163089012 fabH2 +PA4770 PA4770 0.0620731349193617 5478.0 1.30854169135 1.30854169135 0.704720956713728 3464.0 0.19520000000000018 0.19719380272547407 25 5.645926372746881 lldP 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PA0266 0.613224364091475 2765.0 0.19000705455000103 -0.19000705455000103 0.7928683394638559 2160.5 0.08116000000000004 0.0681700875262258 25 1.5966981780407177 davT +PA3706 PA3706 0.657539779668318 2764.0 0.18995892469999898 0.18995892469999898 0.655573611366329 2580.5 0.10002000000000041 0.045588850976235044 25 1.9728271885352564 wspC +PA3696 PA3696 0.669588919364531 2763.0 0.18989521920000102 0.18989521920000102 0.8630458390673291 176.5 0.05465999999999973 0.049314830426555704 25 2.742282960932134 +PA4690 PA4690 0.603073555617845 2762.0 0.189877829300001 0.189877829300001 0.65507019696822 2394.0 0.09541999999999959 0.0491455491372307 25 1.9220017063242851 still frameshift hypothetical protein +PA0323 PA0323 0.8399516399869509 2761.0 0.1897848675 0.1897848675 0.876830281996167 1743.0 0.1075000000000003 0.09182932538138373 25 0.896063073078843 +PA4984 PA4984 0.627774789241947 2760.0 0.189741852000001 -0.189741852000001 0.532541456089778 4000.0 0.1599400000000005 0.07319314061668164 25 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0.04327999999999993 0.031451377818255744 25 -1.347513873474863 +PA3567 PA3567 0.998281687923093 14.0 0.0008987911500000221 0.0008987911500000221 0.78731724841804 618.0 0.08153999999999996 0.07271575941064441 25 -1.1089921841371206 +PA5458 PA5458 0.998281687923093 13.0 0.0008838328000022599 -0.0008838328000022599 0.740599215642366 2593.5 0.0894999999999999 0.05598083749522422 25 -1.5829732309302726 +PA5385 PA5385 0.999186063152634 12.0 0.00080490995000293 -0.00080490995000293 0.755335725510212 2715.5 0.11475999999999993 0.07490732051453076 25 -1.5212810879798007 cdhB +PA4617 PA4617 0.9984113703467611 11.0 0.000750397350000931 0.000750397350000931 0.7300046422619342 858.5 0.0670999999999994 0.04909599440551807 25 -1.3514259860381035 +PA3051 PA3051 0.9989074221776221 10.0 0.000648286900002404 -0.000648286900002404 0.6947202141247271 2651.5 0.09938000000000001 0.05613474859656891 25 -1.7588341547508475 +PA1278 PA1278 0.9988944863919109 9.0 0.0006285930499991821 -0.0006285930499991821 0.579044781902832 4450.0 0.1613599999999993 0.05718728734022447 25 -2.8106142890422547 cobP +PA0113 PA0113 0.9991991967375501 8.0 0.0005364054999992259 0.0005364054999992259 0.7292007378062869 3187.5 0.1192800000000006 0.08905313020888163 25 -1.333401692017768 +PA2769 PA2769 0.9991991967375501 7.0 0.00042900999999862004 0.00042900999999862004 0.601132162714155 3316.0 0.1507400000000002 0.10430415459926186 25 -1.4410834408034723 +PA2813 PA2813 0.9992556615832231 6.0 0.000362855100000559 -0.000362855100000559 0.822196814508769 1233.0 0.07074000000000011 0.04999814996577359 25 -1.4075949799777885 +PA1078 PA1078 0.9992556615832231 5.0 0.00034189965000130896 0.00034189965000130896 0.5689435835636121 5017.0 0.22775999999999974 0.11496531360951173 25 -1.9781453484521512 flgC +PA1182 PA1182 0.9992680321355699 4.0 0.000336375750001672 -0.000336375750001672 0.886601549465272 682.5 0.048660000000000106 0.033101397251475595 25 -1.45986659967486 +PA1520 PA1520 0.9994623983765291 3.0 0.000193089449998851 0.000193089449998851 0.594203990855089 4184.5 0.15665999999999994 0.0907483608667395 25 -1.7241844266450914 +PA3084 PA3084 0.9994623983765291 2.0 0.00019267329999905802 0.00019267329999905802 0.820757902372628 2224.0 0.10466000000000056 0.08985807327855048 25 -1.1625814229976186 +PA2420 PA2420 0.9996691272829309 1.0 0.00012529540000016899 0.00012529540000016899 0.8093389331274808 408.5 0.06671999999999975 0.047165727316912424 25 -1.4119299836625316 diff --git a/pseudomonas_analysis/generic_pathway_summary_E-GEOD-33245.tsv b/pseudomonas_analysis/generic_pathway_summary_E-GEOD-33245.tsv new file mode 100644 index 00000000..afcbc38b --- /dev/null +++ b/pseudomonas_analysis/generic_pathway_summary_E-GEOD-33245.tsv @@ -0,0 +1,170 @@ +pathway Pathway ID Adj P-value (Real) Rank (Real) padj (Real) Median adj p-value (simulated) Rank (simulated) Mean padj (simulated) Std deviation (simulated) Number of experiments (simulated) Z score +KEGG-Module-M00178: Ribosome, bacteria KEGG-Module-M00178: Ribosome, bacteria 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae03060: Protein export - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03060: Protein export - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00149084036332505 0.000718858726894175 25 -0.3062683436381803 +KEGG-Pathway-pae00230: Purine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00230: Purine metabolism - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.0015132917508524624 0.0009883549557142583 25 -0.24547361018472444 +KEGG-Pathway-pae00030: Pentose phosphate pathway - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00030: Pentose phosphate pathway - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.005694837579188571 138.0 0.010111200622122108 0.011455825273375788 25 -0.7717055488737978 +KEGG-Pathway-pae00330: Arginine and proline metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00330: Arginine and proline metabolism - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.00307307648596431 145.0 0.007953537887471284 0.014680067848283972 25 -0.4552336722696522 +KEGG-Pathway-pae03018: RNA degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03018: RNA degradation - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae03010: Ribosome - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03010: Ribosome - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae00620: Pyruvate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00620: Pyruvate metabolism - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.00167075292628915 151.0 0.004236762974577575 0.0065179984532746146 25 -0.4550609062139476 +KEGG-Pathway-pae00020: Citrate cycle (TCA cycle) - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00020: Citrate cycle (TCA cycle) - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae00240: Pyrimidine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00240: Pyrimidine metabolism - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Module-M00360: Aminoacyl-tRNA biosynthesis, prokaryotes KEGG-Module-M00360: Aminoacyl-tRNA biosynthesis, prokaryotes 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae00680: Methane metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00680: Methane metabolism - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.001474301859479602 0.00046223111314822014 25 -0.44052674508084677 +KEGG-Module-M00335: Sec (secretion) system KEGG-Module-M00335: Sec (secretion) system 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.001770094856225919 0.001924199619527974 25 -0.25954592206972343 +KEGG-Module-M00144: NADH:quinone oxidoreductase, prokaryotes KEGG-Module-M00144: NADH:quinone oxidoreductase, prokaryotes 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.002967625777595606 0.005814433925110114 25 -0.2918511256165232 +KEGG-Module-M00157: F-type ATPase, prokaryotes and chloroplasts KEGG-Module-M00157: F-type ATPase, prokaryotes and chloroplasts 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.0013375514174993322 0.0002359146845138336 25 -0.2834699582513304 +KEGG-Module-M00002: Glycolysis, core module involving three-carbon compounds KEGG-Module-M00002: Glycolysis, core module involving three-carbon compounds 0.00127067669172932 159.5 0.00127067669172932 0.00228228795991816 147.0 0.006355303221978068 0.00937754223721834 25 -0.5422131302238743 +KEGG-Module-M00009: Citrate cycle (TCA cycle, Krebs cycle) KEGG-Module-M00009: Citrate cycle (TCA cycle, Krebs cycle) 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Pathway-pae00190: Oxidative phosphorylation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00190: Oxidative phosphorylation - Pseudomonas aeruginosa PAO1 0.00127067669172932 159.5 0.00127067669172932 0.0013554917467396 162.0 0.00133468580730894 0.0002329850088596308 25 -0.2747349105975495 +KEGG-Module-M00011: Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate KEGG-Module-M00011: Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate 0.00127067669172932 159.5 0.00127067669172932 0.0013733138306517099 154.0 0.001390398216396974 0.0003238391526388588 25 -0.36969441061120234 +KEGG-Pathway-pae00010: Glycolysis / Gluconeogenesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00010: Glycolysis / Gluconeogenesis - Pseudomonas aeruginosa PAO1 0.00172463058208833 147.5 0.00172463058208833 0.0014728824047202 153.0 0.0015729031188546538 0.0005446288974599456 25 0.2785887123164171 +KEGG-Pathway-pae00250: Alanine, aspartate and glutamate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00250: Alanine, aspartate and glutamate metabolism - Pseudomonas aeruginosa PAO1 0.00172463058208833 147.5 0.00172463058208833 0.0016497784025459301 152.0 0.002413623303611034 0.0022001811503228968 25 -0.3131527244570694 +KEGG-Pathway-pae00270: Cysteine and methionine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00270: Cysteine and methionine metabolism - Pseudomonas aeruginosa PAO1 0.00172463058208833 147.5 0.00172463058208833 0.00354970426132545 142.0 0.01251338468099733 0.01813659424231015 25 -0.5948610833306475 +KEGG-Pathway-pae01210: 2-Oxocarboxylic acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01210: 2-Oxocarboxylic acid metabolism - Pseudomonas aeruginosa PAO1 0.00172463058208833 147.5 0.00172463058208833 0.00182507370489962 150.0 0.003537172550072197 0.005668647930995594 25 -0.31974855204414276 +KEGG-Pathway-pae02040: Flagellar assembly - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae02040: Flagellar assembly - Pseudomonas aeruginosa PAO1 0.0022490551306847397 143.5 0.0022490551306847397 0.0018754022682380101 149.0 0.01276374179903695 0.028887011819740797 25 -0.36399357378898867 +KEGG-Pathway-pae00400: Phenylalanine, tyrosine and tryptophan biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00400: Phenylalanine, tyrosine and tryptophan biosynthesis - Pseudomonas aeruginosa PAO1 0.0022490551306847397 143.5 0.0022490551306847397 0.00192608689045238 148.0 0.004718449494685213 0.006381286456676947 25 -0.3869743790324075 +KEGG-Pathway-pae00630: Glyoxylate and dicarboxylate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00630: Glyoxylate and dicarboxylate metabolism - Pseudomonas aeruginosa PAO1 0.0022490551306847397 143.5 0.0022490551306847397 0.0213954566527585 118.0 0.035008347253929914 0.029424035042803207 25 -1.1133514514780234 +KEGG-Pathway-pae02030: Bacterial chemotaxis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae02030: Bacterial chemotaxis - Pseudomonas aeruginosa PAO1 0.0022490551306847397 143.5 0.0022490551306847397 0.00809290075422004 133.0 0.035181200587299725 0.0856965454577838 25 -0.38428789959611803 +KEGG-Module-M00156: Cytochrome c oxidase, cbb3-type KEGG-Module-M00156: Cytochrome c oxidase, cbb3-type 0.00262898625875032 141.0 0.00262898625875032 0.00317519962423673 143.0 0.04720625833180748 0.1357907180278766 25 -0.32827922792120334 +KEGG-Module-M00331: Type II general secretion pathway KEGG-Module-M00331: Type II general secretion pathway 0.00314535641168807 140.0 0.00314535641168807 0.0249262536873156 114.0 0.0524967723791304 0.0684735369422478 25 -0.7207370638538284 +KEGG-Pathway-pae00540: Lipopolysaccharide biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00540: Lipopolysaccharide biosynthesis - Pseudomonas aeruginosa PAO1 0.0035598882742757 139.0 0.0035598882742757 0.00312607902135846 144.0 0.007091287015878242 0.008691853384535729 25 -0.4062883467276951 +KEGG-Module-M00010: Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate KEGG-Module-M00010: Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate 0.0041650236593059895 138.0 0.0041650236593059895 0.00249977812620182 146.0 0.003093803968654161 0.0019375393392309594 25 0.5528763566044615 +KEGG-Module-M00048: Inosine monophosphate biosynthesis, PRPP + glutamine => IMP KEGG-Module-M00048: Inosine monophosphate biosynthesis, PRPP + glutamine => IMP 0.0043504562830628205 137.0 0.0043504562830628205 0.0123848840901874 126.0 0.041413898034825244 0.048373793568138215 25 -0.7661884466339344 +KEGG-Module-M00506: CheA-CheYBV (chemotaxis) two-component regulatory system KEGG-Module-M00506: CheA-CheYBV (chemotaxis) two-component regulatory system 0.006542273149581911 135.0 0.006542273149581911 0.0080316649919887 134.0 0.0471942220119478 0.12647743525167346 25 -0.3214166130225036 +KEGG-Module-M00436: Sulfonate transport system KEGG-Module-M00436: Sulfonate transport system 0.006542273149581911 135.0 0.006542273149581911 0.00651403021893309 135.0 0.008909831614110011 0.008389572037477401 25 -0.2822025311841752 +KEGG-Module-M00188: NitT/TauT family transport system KEGG-Module-M00188: NitT/TauT family transport system 0.006542273149581911 135.0 0.006542273149581911 0.0100235996303973 131.0 0.014655618056190638 0.013531045281139567 25 -0.5996096190674659 +KEGG-Pathway-pae03030: DNA replication - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03030: DNA replication - Pseudomonas aeruginosa PAO1 0.00756219795954895 133.0 0.00756219795954895 0.0055877928218353795 139.0 0.007843982236940777 0.007636999318323639 25 -0.03689725056223782 +KEGG-Module-M00034: Methionine salvage pathway KEGG-Module-M00034: Methionine salvage pathway 0.00887065933818733 132.0 0.00887065933818733 0.0656470927716058 97.0 0.08319319214443112 0.06702814925730734 25 -1.1088256744332117 +KEGG-Module-M00125: Riboflavin biosynthesis, GTP => riboflavin/FMN/FAD KEGG-Module-M00125: Riboflavin biosynthesis, GTP => riboflavin/FMN/FAD 0.00888538380651945 131.0 0.00888538380651945 0.0137989356273238 124.0 0.02196413844675591 0.026157135489003516 25 -0.500007145114754 +KEGG-Pathway-pae03440: Homologous recombination - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03440: Homologous recombination - Pseudomonas aeruginosa PAO1 0.009736269363717829 130.0 0.009736269363717829 0.0156986465379031 121.0 0.021186328829687486 0.016122575526249964 25 -0.710187987479249 +KEGG-Pathway-pae00550: Peptidoglycan biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00550: Peptidoglycan biosynthesis - Pseudomonas aeruginosa PAO1 0.0103974406299988 128.0 0.0103974406299988 0.00476660555633902 141.0 0.012258941957972325 0.016558899319783188 25 -0.11241697241009001 +KEGG-Pathway-pae00260: Glycine, serine and threonine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00260: Glycine, serine and threonine metabolism - Pseudomonas aeruginosa PAO1 0.0103974406299988 128.0 0.0103974406299988 0.0216723444826683 117.0 0.03563565049165807 0.04527069314533861 25 -0.5574955475197529 +KEGG-Pathway-pae00300: Lysine biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00300: Lysine biosynthesis - Pseudomonas aeruginosa PAO1 0.0103974406299988 128.0 0.0103974406299988 0.006355318724874871 137.0 0.023314383447898268 0.030569913512195755 25 -0.42253776127780995 +KEGG-Pathway-pae00523: Polyketide sugar unit biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00523: Polyketide sugar unit biosynthesis - Pseudomonas aeruginosa PAO1 0.0118354318402972 126.0 0.0118354318402972 0.00636280208014683 136.0 0.012682776120661914 0.018165085512262574 25 -0.04664686438127161 +KEGG-Module-M00119: Pantothenate biosynthesis, valine/L-aspartate => pantothenate KEGG-Module-M00119: Pantothenate biosynthesis, valine/L-aspartate => pantothenate 0.0122122432125529 125.0 0.0122122432125529 0.0332258571877949 107.0 0.04961672225689836 0.03823685019722511 25 -0.9782311788605419 +KEGG-Pathway-pae00520: Amino sugar and nucleotide sugar metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00520: Amino sugar and nucleotide sugar metabolism - Pseudomonas aeruginosa PAO1 0.013047205273190001 124.0 0.013047205273190001 0.23576043215409498 72.0 0.2806713814965722 0.19912632916459025 25 -1.343991913807512 +KEGG-Module-M00115: NAD biosynthesis, aspartate => NAD KEGG-Module-M00115: NAD biosynthesis, aspartate => NAD 0.0139957626241365 123.0 0.0139957626241365 0.0123747130298449 127.0 0.015528622884420912 0.0109603728904736 25 -0.1398547545418573 +KEGG-Pathway-pae00760: Nicotinate and nicotinamide metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00760: Nicotinate and nicotinamide metabolism - Pseudomonas aeruginosa PAO1 0.0154566316349608 122.0 0.0154566316349608 0.004922091160623271 140.0 0.007862871413071537 0.006533889103062222 25 1.1622113724474314 +KEGG-Module-M00018: Threonine biosynthesis, aspartate => homoserine => threonine KEGG-Module-M00018: Threonine biosynthesis, aspartate => homoserine => threonine 0.015776089615656998 121.0 0.015776089615656998 0.0171095925082258 120.0 0.05044202108988978 0.059452124032135074 25 -0.5830898733827432 +KEGG-Module-M00050: Guanine ribonucleotide biosynthesis IMP => GDP,GTP KEGG-Module-M00050: Guanine ribonucleotide biosynthesis IMP => GDP,GTP 0.0162027587060061 119.5 0.0162027587060061 0.0135254101640656 125.0 0.02952643611709124 0.040336870273154087 25 -0.33031014356987975 +KEGG-Pathway-pae00364: Fluorobenzoate degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00364: Fluorobenzoate degradation - Pseudomonas aeruginosa PAO1 0.0162027587060061 119.5 0.0162027587060061 0.0260651629072682 112.0 0.037575189597868916 0.032830143567333804 25 -0.6510002263020415 +KEGG-Pathway-pae00640: Propanoate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00640: Propanoate metabolism - Pseudomonas aeruginosa PAO1 0.0173714217840599 118.0 0.0173714217840599 0.0351273196684547 105.0 0.05438223240157684 0.057989295765483805 25 -0.638235214429805 +KEGG-Pathway-pae00770: Pantothenate and CoA biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00770: Pantothenate and CoA biosynthesis - Pseudomonas aeruginosa PAO1 0.0198465513191889 117.0 0.0198465513191889 0.0111040352579654 129.0 0.017826092697166757 0.016069039233880027 25 0.12573611854542005 +KEGG-Pathway-pae03430: Mismatch repair - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03430: Mismatch repair - Pseudomonas aeruginosa PAO1 0.0204006720569179 116.0 0.0204006720569179 0.0290032607216196 111.0 0.06127704401528583 0.0659762043225446 25 -0.6195623464261667 +KEGG-Module-M00332: Type III secretion system KEGG-Module-M00332: Type III secretion system 0.0210206694713737 115.0 0.0210206694713737 0.0120864749994892 128.0 0.03661074940159287 0.0588514719085115 25 -0.26490552274469836 +KEGG-Pathway-pae00521: Streptomycin biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00521: Streptomycin biosynthesis - Pseudomonas aeruginosa PAO1 0.0258673469387755 114.0 0.0258673469387755 0.0103654875426919 130.0 0.015989497181773196 0.014021669844917036 25 0.7044702853692638 +KEGG-Pathway-pae01220: Degradation of aromatic compounds - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01220: Degradation of aromatic compounds - Pseudomonas aeruginosa PAO1 0.0289118701189835 113.0 0.0289118701189835 0.0100165955429113 132.0 0.05029626832295344 0.09853383009672295 25 -0.21702595121876975 +KEGG-Module-M00008: Entner-Doudoroff pathway, glucose-6P => glyceraldehyde-3P + pyruvate KEGG-Module-M00008: Entner-Doudoroff pathway, glucose-6P => glyceraldehyde-3P + pyruvate 0.0326308060480801 112.0 0.0326308060480801 0.0501310316371706 103.0 0.06797922463148624 0.05325946603465897 25 -0.6637020836897409 +KEGG-Module-M00452: CusS-CusR (copper tolerance) two-component regulatory system KEGG-Module-M00452: CusS-CusR (copper tolerance) two-component regulatory system 0.033326928522309 111.0 0.033326928522309 0.130459014123511 87.0 0.16636767289301072 0.11436761720289441 25 -1.163272853142338 +KEGG-Pathway-pae00450: Selenocompound metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00450: Selenocompound metabolism - Pseudomonas aeruginosa PAO1 0.0339258936777439 110.0 0.0339258936777439 0.0227296347241327 116.0 0.046362933708505034 0.05754257211376189 25 -0.21613632435778254 +KEGG-Module-M00210: Putative ABC transport system KEGG-Module-M00210: Putative ABC transport system 0.0353395622021334 108.5 0.0353395622021334 0.0155704311523789 122.0 0.023531289911938206 0.023884680732037433 25 0.4943868592037032 +KEGG-Module-M00616: Sulfate-sulfur assimilation KEGG-Module-M00616: Sulfate-sulfur assimilation 0.0353395622021334 108.5 0.0353395622021334 0.0860553493681095 93.0 0.12290110699312279 0.09843827100210696 25 -0.8895071388354153 +KEGG-Pathway-pae00900: Terpenoid backbone biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00900: Terpenoid backbone biosynthesis - Pseudomonas aeruginosa PAO1 0.0371512624058449 107.0 0.0371512624058449 0.0194175996731818 119.0 0.03859306825903618 0.04736447759414015 25 -0.030440657776190982 +KEGG-Pathway-pae00440: Phosphonate and phosphinate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00440: Phosphonate and phosphinate metabolism - Pseudomonas aeruginosa PAO1 0.0372896141215107 106.0 0.0372896141215107 0.0346581354333292 106.0 0.055642822393000425 0.08777901149356815 25 -0.20908424416279195 +KEGG-Module-M00240: Iron complex transport system KEGG-Module-M00240: Iron complex transport system 0.0376084860173578 105.0 0.0376084860173578 0.0426912363972372 104.0 0.08079764583549337 0.12245209735423568 25 -0.35270249143381976 +KEGG-Module-M00258: Putative ABC transport system KEGG-Module-M00258: Putative ABC transport system 0.0397230057134592 104.0 0.0397230057134592 0.17696611652913197 81.0 0.19518613659643744 0.12695290400798218 25 -1.2245732549229713 +KEGG-Module-M00016: Lysine biosynthesis, succinyl-DAP pathway, aspartate => lysine KEGG-Module-M00016: Lysine biosynthesis, succinyl-DAP pathway, aspartate => lysine 0.0402308285859697 102.5 0.0402308285859697 0.0331857208634652 108.0 0.07751507358362901 0.08082080266097198 25 -0.46131990490195557 +KEGG-Pathway-pae00670: One carbon pool by folate - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00670: One carbon pool by folate - Pseudomonas aeruginosa PAO1 0.0402308285859697 102.5 0.0402308285859697 0.0256440517939034 113.0 0.05078446429287861 0.058928521125399466 25 -0.1790921527531779 +KEGG-Pathway-pae00480: Glutathione metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00480: Glutathione metabolism - Pseudomonas aeruginosa PAO1 0.0415862374434717 101.0 0.0415862374434717 0.031502964681619 109.0 0.06819961970262269 0.07948152062334864 25 -0.33483735653810565 +KEGG-Pathway-pae00650: Butanoate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00650: Butanoate metabolism - Pseudomonas aeruginosa PAO1 0.0417234893016694 100.0 0.0417234893016694 0.0869039470682181 92.0 0.1297191904728071 0.11736033500718553 25 -0.7497908144668305 +KEGG-Module-M00529: Denitrification, nitrate => nitrogen KEGG-Module-M00529: Denitrification, nitrate => nitrogen 0.0436741988259453 98.0 0.0436741988259453 0.474625267665953 40.0 0.4387428157232265 0.2688239106937652 25 -1.4696185911354052 +KEGG-Module-M00024: Phenylalanine biosynthesis, chorismate => phenylalanine KEGG-Module-M00024: Phenylalanine biosynthesis, chorismate => phenylalanine 0.0436741988259453 98.0 0.0436741988259453 0.0593417108145001 100.0 0.0597565147526286 0.017420912790646267 25 -0.923161496756835 +KEGG-Module-M00082: Fatty acid biosynthesis, initiation KEGG-Module-M00082: Fatty acid biosynthesis, initiation 0.0436741988259453 98.0 0.0436741988259453 0.19278284767515302 79.0 0.26046329618350134 0.21020829391480536 25 -1.031306107481267 +KEGG-Module-M00053: Pyrimidine deoxyribonuleotide biosynthesis, CDP/CTP => dCDP/dCTP,dTDP/dTTP KEGG-Module-M00053: Pyrimidine deoxyribonuleotide biosynthesis, CDP/CTP => dCDP/dCTP,dTDP/dTTP 0.0513285723991032 96.0 0.0513285723991032 0.062034700967822 98.0 0.08790266092635832 0.060626407532505255 25 -0.6032699283335513 +KEGG-Module-M00176: Assimilatory sulfate reduction, sulfate => H2S KEGG-Module-M00176: Assimilatory sulfate reduction, sulfate => H2S 0.0547806338391659 95.0 0.0547806338391659 0.0748197080377011 95.0 0.09852886297631493 0.08432332482383188 25 -0.5188152771317751 +KEGG-Pathway-pae00460: Cyanoamino acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00460: Cyanoamino acid metabolism - Pseudomonas aeruginosa PAO1 0.05881240401564499 94.0 0.05881240401564499 0.24503551310310998 70.0 0.2924517417246776 0.20940282211425795 25 -1.1157411125125634 +KEGG-Module-M00049: Adenine ribonucleotide biosynthesis, IMP => ADP,ATP KEGG-Module-M00049: Adenine ribonucleotide biosynthesis, IMP => ADP,ATP 0.0659465118492434 92.0 0.0659465118492434 0.059510090145462005 99.0 0.10614458682400191 0.09900084061092623 25 -0.4060377136870699 +KEGG-Module-M00083: Fatty acid biosynthesis, elongation KEGG-Module-M00083: Fatty acid biosynthesis, elongation 0.0659465118492434 92.0 0.0659465118492434 0.14062608996057 84.0 0.14446691876869283 0.06426313432869331 25 -1.2218577220001903 +KEGG-Module-M00019: Valine/isoleucine biosynthesis, pyruvate => valine / 2-oxobutanoate => isoleucine KEGG-Module-M00019: Valine/isoleucine biosynthesis, pyruvate => valine / 2-oxobutanoate => isoleucine 0.0659465118492434 92.0 0.0659465118492434 0.0296015413820365 110.0 0.04114605441341662 0.028040072202532556 25 0.884464820799813 +KEGG-Pathway-pae00401: Novobiocin biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00401: Novobiocin biosynthesis - Pseudomonas aeruginosa PAO1 0.0726321764515083 90.0 0.0726321764515083 0.161310484213387 82.0 0.1762459616176315 0.11163112016717523 25 -0.928180107939027 +KEGG-Pathway-pae00750: Vitamin B6 metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00750: Vitamin B6 metabolism - Pseudomonas aeruginosa PAO1 0.0814453371011112 89.0 0.0814453371011112 0.0762924213117637 94.0 0.08261648680029715 0.042413738560353215 25 -0.027612508091439565 +KEGG-Module-M00533: Homoprotocatechuate degradation, homoprotocatechuate => 2-oxohept-3-enedioate KEGG-Module-M00533: Homoprotocatechuate degradation, homoprotocatechuate => 2-oxohept-3-enedioate 0.0822909332578813 87.5 0.0822909332578813 0.0582029763091591 101.0 0.10112169820013676 0.11475765732486715 25 -0.1640915768169396 +KEGG-Pathway-pae00061: Fatty acid biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00061: Fatty acid biosynthesis - Pseudomonas aeruginosa PAO1 0.0822909332578813 87.5 0.0822909332578813 0.125693035835024 88.0 0.17466898896582642 0.1339021282237529 25 -0.6898923634251706 +KEGG-Pathway-pae00910: Nitrogen metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00910: Nitrogen metabolism - Pseudomonas aeruginosa PAO1 0.104295440074448 85.5 0.104295440074448 0.600279728723511 24.0 0.5810780805570769 0.24282514764668542 25 -1.9634813160964508 +KEGG-Pathway-pae00627: Aminobenzoate degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00627: Aminobenzoate degradation - Pseudomonas aeruginosa PAO1 0.104295440074448 85.5 0.104295440074448 0.0908013831677849 90.0 0.10833801504812024 0.07920102134924356 25 -0.051041955075884174 +KEGG-Module-M00023: Tryptophan biosynthesis, chorismate => tryptophan KEGG-Module-M00023: Tryptophan biosynthesis, chorismate => tryptophan 0.10518587801615499 84.0 0.10518587801615499 0.0141391357892482 123.0 0.03696791671895316 0.04715794866014678 25 1.4465845787489244 +KEGG-Module-M00087: beta-Oxidation KEGG-Module-M00087: beta-Oxidation 0.128373358709171 83.0 0.128373358709171 0.41948172012887003 46.0 0.476757498895167 0.25581629574939063 25 -1.361852805996726 +KEGG-Pathway-pae00362: Benzoate degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00362: Benzoate degradation - Pseudomonas aeruginosa PAO1 0.146057874452936 80.5 0.146057874452936 0.470540112841596 41.0 0.47832376216994754 0.23304159128320906 25 -1.4257793464567359 +KEGG-Pathway-pae00310: Lysine degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00310: Lysine degradation - Pseudomonas aeruginosa PAO1 0.146057874452936 80.5 0.146057874452936 0.123614065671496 89.0 0.15996121162924676 0.10613139621461185 25 -0.13100117092774655 +KEGG-Pathway-pae00281: Geraniol degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00281: Geraniol degradation - Pseudomonas aeruginosa PAO1 0.146057874452936 80.5 0.146057874452936 0.399103784384915 48.0 0.40708913321993867 0.21707581832783454 25 -1.2024888851174813 +KEGG-Module-M00324: Dipeptide transport system KEGG-Module-M00324: Dipeptide transport system 0.146057874452936 80.5 0.146057874452936 0.4139206269607729 47.0 0.38355282024891096 0.2342850652958274 25 -1.0137007474039992 +KEGG-Module-M00193: Putative spermidine/putrescine transport system KEGG-Module-M00193: Putative spermidine/putrescine transport system 0.164420848576717 78.0 0.164420848576717 0.259633849699142 67.5 0.2736303708461895 0.16358689126177284 25 -0.6675933592668787 +KEGG-Module-M00200: Putative sorbitol/mannitol transport system KEGG-Module-M00200: Putative sorbitol/mannitol transport system 0.166808067029317 76.5 0.166808067029317 0.18974281020652 80.0 0.2182779751807735 0.10122925589074912 25 -0.5084489429321203 +KEGG-Pathway-pae00740: Riboflavin metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00740: Riboflavin metabolism - Pseudomonas aeruginosa PAO1 0.166808067029317 76.5 0.166808067029317 0.13711307600280498 85.0 0.1655583741553912 0.10605566680395898 25 0.011783367278580342 +KEGG-Pathway-pae00500: Starch and sucrose metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00500: Starch and sucrose metabolism - Pseudomonas aeruginosa PAO1 0.16966218362808402 75.0 0.16966218362808402 0.21088155637168 76.0 0.21672330474325802 0.1344578280775693 25 -0.3500065543824211 +KEGG-Pathway-pae00290: Valine, leucine and isoleucine biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00290: Valine, leucine and isoleucine biosynthesis - Pseudomonas aeruginosa PAO1 0.172891907187323 74.0 0.172891907187323 0.14376691873887398 83.0 0.1656351502119545 0.0901828441510612 25 0.08046715585076299 +KEGG-Pathway-pae00340: Histidine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00340: Histidine metabolism - Pseudomonas aeruginosa PAO1 0.182809954422832 73.0 0.182809954422832 0.346395950780572 56.0 0.32126964193385055 0.126737381834542 25 -1.0924928817906325 +KEGG-Module-M00260: DNA polymerase III complex, bacteria KEGG-Module-M00260: DNA polymerase III complex, bacteria 0.186970998925886 72.0 0.186970998925886 0.1318907182361 86.0 0.14355315054876222 0.07589050391765759 25 0.5721117417303335 +KEGG-Pathway-pae01053: Biosynthesis of siderophore group nonribosomal peptides - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01053: Biosynthesis of siderophore group nonribosomal peptides - Pseudomonas aeruginosa PAO1 0.202778743193817 71.0 0.202778743193817 0.425464912280702 45.0 0.3960253790509374 0.2385377214888476 25 -0.8101302999414928 +KEGG-Pathway-pae00930: Caprolactam degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00930: Caprolactam degradation - Pseudomonas aeruginosa PAO1 0.22121217168730703 69.0 0.22121217168730703 0.552984997577693 28.0 0.5788999223558949 0.16999075253703544 25 -2.1041600518278747 +KEGG-Module-M00570: Isoleucine biosynthesis, threonine => 2-oxobutanoate => isoleucine KEGG-Module-M00570: Isoleucine biosynthesis, threonine => 2-oxobutanoate => isoleucine 0.22121217168730703 69.0 0.22121217168730703 0.20676048248133302 77.0 0.2113810827297884 0.09593268727392683 25 0.10247903229737408 +KEGG-Module-M00299: Spermidine/putrescine transport system KEGG-Module-M00299: Spermidine/putrescine transport system 0.22121217168730703 69.0 0.22121217168730703 0.0528230321996717 102.0 0.10297674317558268 0.14733948357279827 25 0.8024694104028535 +KEGG-Module-M00185: Sulfate transport system KEGG-Module-M00185: Sulfate transport system 0.22405675974416503 67.0 0.22405675974416503 0.47473577021665103 39.0 0.49652889656880583 0.13809097411999396 25 -1.9731350188599328 +KEGG-Module-M00124: Pyridoxal biosynthesis, erythrose-4P => pyridoxal-5P KEGG-Module-M00124: Pyridoxal biosynthesis, erythrose-4P => pyridoxal-5P 0.225960049550945 66.0 0.225960049550945 0.0697831864713724 96.0 0.09126942763653681 0.05916932979749445 25 2.27635875504055 +KEGG-Module-M00230: Glutamate/aspartate transport system KEGG-Module-M00230: Glutamate/aspartate transport system 0.22935115881982102 64.5 0.22935115881982102 0.47867926404773703 38.0 0.4522548517170604 0.19284602251879382 25 -1.1558635743991885 +KEGG-Pathway-pae04122: Sulfur relay system - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae04122: Sulfur relay system - Pseudomonas aeruginosa PAO1 0.22935115881982102 64.5 0.22935115881982102 0.0239944344270441 115.0 0.06066777719943805 0.07193846344474958 25 2.344828809833223 +KEGG-Pathway-pae00730: Thiamine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00730: Thiamine metabolism - Pseudomonas aeruginosa PAO1 0.242496985774483 63.0 0.242496985774483 0.0874793698424606 91.0 0.0825094156753855 0.04835479864689705 25 3.3086182669765702 +KEGG-Pathway-pae00350: Tyrosine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00350: Tyrosine metabolism - Pseudomonas aeruginosa PAO1 0.271397261933044 62.0 0.271397261933044 0.62690889807388 19.0 0.5793005724992474 0.2477305654088435 25 -1.2428959262982082 +KEGG-Pathway-pae03410: Base excision repair - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03410: Base excision repair - Pseudomonas aeruginosa PAO1 0.282353980442815 61.0 0.282353980442815 0.39185931260354495 50.0 0.48667087907828277 0.25503672743656647 25 -0.8011273540446683 +KEGG-Module-M00300: Putrescine transport system KEGG-Module-M00300: Putrescine transport system 0.283707450444293 60.0 0.283707450444293 0.366786689827352 54.0 0.4390081182000858 0.18964089696895495 25 -0.8189197068669011 +KEGG-Module-M00432: Leucine biosynthesis, 2-oxoisovalerate => 2-oxoisocaproate KEGG-Module-M00432: Leucine biosynthesis, 2-oxoisovalerate => 2-oxoisocaproate 0.291010462042518 58.5 0.291010462042518 0.3924079617477971 49.0 0.4096325811350548 0.1631669633687014 25 -0.7269983864594665 +KEGG-Pathway-pae00361: Chlorocyclohexane and chlorobenzene degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00361: Chlorocyclohexane and chlorobenzene degradation - Pseudomonas aeruginosa PAO1 0.291010462042518 58.5 0.291010462042518 0.618627118004453 21.0 0.6569104088289136 0.16850421432961 25 -2.1714587272616286 +KEGG-Pathway-pae03420: Nucleotide excision repair - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03420: Nucleotide excision repair - Pseudomonas aeruginosa PAO1 0.291468494244461 57.0 0.291468494244461 0.295204904624401 63.0 0.36620451549905153 0.21593831678581926 25 -0.3460989340243783 +KEGG-Pathway-pae00660: C5-Branched dibasic acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00660: C5-Branched dibasic acid metabolism - Pseudomonas aeruginosa PAO1 0.30120794590439304 56.0 0.30120794590439304 0.29937956730502696 62.0 0.33329514846925706 0.11492321506219143 25 -0.2792055769367384 +KEGG-Pathway-pae00590: Arachidonic acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00590: Arachidonic acid metabolism - Pseudomonas aeruginosa PAO1 0.302025785214648 55.0 0.302025785214648 0.563845637672778 27.0 0.5564796861560366 0.11451574823032305 25 -2.221999199879574 +KEGG-Pathway-pae00471: D-Glutamine and D-glutamate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00471: D-Glutamine and D-glutamate metabolism - Pseudomonas aeruginosa PAO1 0.304563680696142 54.0 0.304563680696142 0.238000092063547 71.0 0.25720168473900773 0.09227977664483973 25 0.5132435044724691 +KEGG-Module-M00647: Multidrug resistance, efflux pump MexAB-OprM/SmeDEF/AcrAB-TolC KEGG-Module-M00647: Multidrug resistance, efflux pump MexAB-OprM/SmeDEF/AcrAB-TolC 0.341236424394319 53.0 0.341236424394319 0.199274501936572 78.0 0.21070438961385426 0.07394605619948644 25 1.7652332185008577 +KEGG-Module-M00349: Microcin C transport system KEGG-Module-M00349: Microcin C transport system 0.34799137628793103 52.0 0.34799137628793103 0.276160555285737 65.0 0.32953379695832846 0.19181670001799078 25 0.09622509055713817 +KEGG-Pathway-pae00051: Fructose and mannose metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00051: Fructose and mannose metabolism - Pseudomonas aeruginosa PAO1 0.353861219890377 51.0 0.353861219890377 0.7004633324465729 12.0 0.6705735637567103 0.17355021260037395 25 -1.8249032318710674 +KEGG-Module-M00028: Ornithine biosynthesis, glutamate => ornithine KEGG-Module-M00028: Ornithine biosynthesis, glutamate => ornithine 0.360448621553885 50.0 0.360448621553885 0.502952574608942 35.0 0.5289984659674796 0.14247679967510513 25 -1.1829985288688734 +KEGG-Pathway-pae00052: Galactose metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00052: Galactose metabolism - Pseudomonas aeruginosa PAO1 0.371911666245925 47.5 0.371911666245925 0.21843156291192103 75.0 0.2528433466321065 0.13253806961979803 25 0.8983707093017183 +KEGG-Pathway-pae00561: Glycerolipid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00561: Glycerolipid metabolism - Pseudomonas aeruginosa PAO1 0.371911666245925 47.5 0.371911666245925 0.7633381173418149 7.0 0.7608195398814941 0.16419547840005053 25 -2.368566281027684 +KEGG-Module-M00307: Pyruvate oxidation, pyruvate => acetyl-CoA KEGG-Module-M00307: Pyruvate oxidation, pyruvate => acetyl-CoA 0.371911666245925 47.5 0.371911666245925 0.339937782989674 57.0 0.32341992696220134 0.15048344820626997 25 0.3222396872329458 +KEGG-Pathway-pae02060: Phosphotransferase system (PTS) - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae02060: Phosphotransferase system (PTS) - Pseudomonas aeruginosa PAO1 0.371911666245925 47.5 0.371911666245925 0.49158257825370705 36.0 0.4885596709505253 0.07637816424394162 25 -1.527242843020451 +KEGG-Pathway-pae00625: Chloroalkane and chloroalkene degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00625: Chloroalkane and chloroalkene degradation - Pseudomonas aeruginosa PAO1 0.4219839279974289 45.0 0.4219839279974289 0.33925524440429605 58.0 0.3544090661342983 0.11978835964554548 25 0.5641187679928589 +KEGG-Module-M00222: Phosphate transport system KEGG-Module-M00222: Phosphate transport system 0.43930177103256396 43.5 0.43930177103256396 0.532939934035499 30.0 0.5373441798634144 0.1460689760163469 25 -0.6712062445065564 +KEGG-Module-M00021: Cysteine biosynthesis, serine => cysteine KEGG-Module-M00021: Cysteine biosynthesis, serine => cysteine 0.43930177103256396 43.5 0.43930177103256396 0.269675925925926 66.0 0.3070221043660171 0.10039843393284784 25 1.3175471118904403 +KEGG-Pathway-pae00430: Taurine and hypotaurine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00430: Taurine and hypotaurine metabolism - Pseudomonas aeruginosa PAO1 0.456633289590418 42.0 0.456633289590418 0.82189405665085 4.0 0.7977907298912104 0.12177185366890521 25 -2.801611620599875 +KEGG-Pathway-pae00312: beta-Lactam resistance - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00312: beta-Lactam resistance - Pseudomonas aeruginosa PAO1 0.45805754041956603 41.0 0.45805754041956603 0.22820705176294098 73.0 0.22630089278060844 0.10530863240407838 25 2.2007374167550404 +KEGG-Module-M00254: ABC-2 type transport system KEGG-Module-M00254: ABC-2 type transport system 0.466808428301782 39.0 0.466808428301782 0.33862462223311307 59.0 0.38779739664056245 0.18624971919118866 25 0.4242209438185155 +KEGG-Pathway-pae00130: Ubiquinone and other terpenoid-quinone biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00130: Ubiquinone and other terpenoid-quinone biosynthesis - Pseudomonas aeruginosa PAO1 0.466808428301782 39.0 0.466808428301782 0.220088543081909 74.0 0.25357039442544127 0.19535781559528295 25 1.091525482236655 +KEGG-Module-M00323: Urea transport system KEGG-Module-M00323: Urea transport system 0.466808428301782 39.0 0.466808428301782 0.25639753517835395 69.0 0.33745931462058615 0.18668898242274198 25 0.6928588500648384 +KEGG-Pathway-pae00380: Tryptophan metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00380: Tryptophan metabolism - Pseudomonas aeruginosa PAO1 0.484234734742781 37.0 0.484234734742781 0.60924539386568 22.0 0.5730639728746797 0.19982421893042943 25 -0.44453689651515854 +KEGG-Pathway-pae01212: Fatty acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01212: Fatty acid metabolism - Pseudomonas aeruginosa PAO1 0.48918623702894604 35.5 0.48918623702894604 0.45387533999222895 42.0 0.4574143613781229 0.21733765709860522 25 0.14618670356057234 +KEGG-Module-M00328: Hemophore/metalloprotease transport system KEGG-Module-M00328: Hemophore/metalloprotease transport system 0.48918623702894604 35.5 0.48918623702894604 0.5276070611310889 31.0 0.4967201461352382 0.21283558604518857 25 -0.03539778871702673 +KEGG-Module-M00190: Iron(III) transport system KEGG-Module-M00190: Iron(III) transport system 0.500404256739997 34.0 0.500404256739997 0.35573365709920296 55.0 0.386110604837726 0.1869038709752329 25 0.6115103518504243 +KEGG-Pathway-pae00071: Fatty acid degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00071: Fatty acid degradation - Pseudomonas aeruginosa PAO1 0.519365329262281 33.0 0.519365329262281 0.689980590321933 13.0 0.6462191520897725 0.18123018474470165 25 -0.699959683902492 +KEGG-Module-M00572: Pimeloyl-ACP biosynthesis, BioC-BioH pathway, malonyl-ACP => pimeloyl-ACP KEGG-Module-M00572: Pimeloyl-ACP biosynthesis, BioC-BioH pathway, malonyl-ACP => pimeloyl-ACP 0.5826382124619971 32.0 0.5826382124619971 0.5652901699273511 26.0 0.5309173373273203 0.17025029412080903 25 0.30379316171974347 +KEGG-Module-M00235: Arginine/ornithine transport system KEGG-Module-M00235: Arginine/ornithine transport system 0.600223551291954 31.0 0.600223551291954 0.48315582865456996 37.0 0.4516249420272264 0.1432641934541455 25 1.0372348154969335 +KEGG-Module-M00334: Type VI secretion system KEGG-Module-M00334: Type VI secretion system 0.6115243697478989 30.0 0.6115243697478989 0.536739033057091 29.0 0.495742287955694 0.282876197363926 25 0.40930301973498634 +KEGG-Pathway-pae00920: Sulfur metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00920: Sulfur metabolism - Pseudomonas aeruginosa PAO1 0.619629772680202 29.0 0.619629772680202 0.259633849699142 67.5 0.28942791001422014 0.27121582185286236 25 1.2174874622363296 +KEGG-Pathway-pae00790: Folate biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00790: Folate biosynthesis - Pseudomonas aeruginosa PAO1 0.6198817276742271 26.0 0.6198817276742271 0.37371395740359703 52.0 0.4072827197004672 0.24022970906954233 25 0.884982164767207 +KEGG-Module-M00208: Glycine betaine/proline transport system KEGG-Module-M00208: Glycine betaine/proline transport system 0.6198817276742271 26.0 0.6198817276742271 0.427962148473944 44.0 0.4892675963999903 0.2201806768228129 25 0.5932134152687095 +KEGG-Module-M00238: D-Methionine transport system KEGG-Module-M00238: D-Methionine transport system 0.6198817276742271 26.0 0.6198817276742271 0.6608065848106679 16.0 0.6309343506777253 0.11614213406836867 25 -0.09516462817009981 +KEGG-Module-M00223: Phosphonate transport system KEGG-Module-M00223: Phosphonate transport system 0.6198817276742271 26.0 0.6198817276742271 0.770075297136683 6.0 0.7771644651845833 0.16178536203902083 25 -0.9721691476168364 +KEGG-Module-M00045: Histidine degradation, histidine => N-formiminoglutamate => glutamate KEGG-Module-M00045: Histidine degradation, histidine => N-formiminoglutamate => glutamate 0.6198817276742271 26.0 0.6198817276742271 0.7169621549614921 10.0 0.6618860225101635 0.17326829782715636 25 -0.24242342865189176 +KEGG-Pathway-pae00360: Phenylalanine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00360: Phenylalanine metabolism - Pseudomonas aeruginosa PAO1 0.636902821965288 23.0 0.636902821965288 0.713530411810919 11.0 0.6682545529974471 0.14983013263031691 25 -0.20924850350039187 +KEGG-Pathway-pae00780: Biotin metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00780: Biotin metabolism - Pseudomonas aeruginosa PAO1 0.637872182348323 22.0 0.637872182348323 0.5848830075797911 25.0 0.5584919883881578 0.1640105488008278 25 0.4839944414585393 +KEGG-Pathway-pae00564: Glycerophospholipid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00564: Glycerophospholipid metabolism - Pseudomonas aeruginosa PAO1 0.647498647335737 21.0 0.647498647335737 0.6650416846765429 15.0 0.6405852060429024 0.20871096102986503 25 0.03312447635103075 +KEGG-Pathway-pae00562: Inositol phosphate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00562: Inositol phosphate metabolism - Pseudomonas aeruginosa PAO1 0.6750239448376569 19.5 0.6750239448376569 0.627347247721197 18.0 0.5934937076054211 0.17463825487790596 25 0.4668521068836591 +KEGG-Pathway-pae00280: Valine, leucine and isoleucine degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00280: Valine, leucine and isoleucine degradation - Pseudomonas aeruginosa PAO1 0.6750239448376569 19.5 0.6750239448376569 0.302049559113731 61.0 0.3636005827182378 0.23521209971144402 25 1.3240108076985426 +KEGG-Module-M00644: Multidrug resistance, efflux pump MexHI-OprD KEGG-Module-M00644: Multidrug resistance, efflux pump MexHI-OprD 0.6777687475138199 18.0 0.6777687475138199 0.5074094079519029 33.0 0.49341284633629223 0.2163765867453376 25 0.852014092423519 +KEGG-Pathway-pae00072: Synthesis and degradation of ketone bodies - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00072: Synthesis and degradation of ketone bodies - Pseudomonas aeruginosa PAO1 0.6798002130276971 17.0 0.6798002130276971 0.450869605852316 43.0 0.4676761923871115 0.1889178617810603 25 1.1228372936298594 +KEGG-Module-M00236: Putative polar amino acid transport system KEGG-Module-M00236: Putative polar amino acid transport system 0.6884935911618512 15.5 0.6884935911618512 0.37543800158245705 51.0 0.4072927670447832 0.17829736109789868 25 1.5771451825507814 +KEGG-Module-M00530: Dissimilatory nitrate reduction, nitrate => ammonia KEGG-Module-M00530: Dissimilatory nitrate reduction, nitrate => ammonia 0.6884935911618512 15.5 0.6884935911618512 0.37155268664355895 53.0 0.49463902742082516 0.3115284585025195 25 0.6222691970835088 +KEGG-Pathway-pae01040: Biosynthesis of unsaturated fatty acids - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01040: Biosynthesis of unsaturated fatty acids - Pseudomonas aeruginosa PAO1 0.753869932512153 14.0 0.753869932512153 0.6477430555555551 17.0 0.6242187325597538 0.11377415768236156 25 1.1395487568834712 +KEGG-Pathway-pae03070: Bacterial secretion system - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03070: Bacterial secretion system - Pseudomonas aeruginosa PAO1 0.768420393062828 13.0 0.768420393062828 0.608553542740014 23.0 0.5782043374438753 0.1921498289851643 25 0.9899361171621918 +KEGG-Pathway-pae00643: Styrene degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00643: Styrene degradation - Pseudomonas aeruginosa PAO1 0.7893763942716059 12.0 0.7893763942716059 0.863414975181189 2.0 0.8179532400011721 0.1672709870360967 25 -0.17084161596654765 +KEGG-Module-M00237: Branched-chain amino acid transport system KEGG-Module-M00237: Branched-chain amino acid transport system 0.797971908299229 11.0 0.797971908299229 0.720654142414945 9.0 0.6085308014965165 0.23484580837961289 25 0.806661647954531 +KEGG-Pathway-pae00860: Porphyrin and chlorophyll metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00860: Porphyrin and chlorophyll metabolism - Pseudomonas aeruginosa PAO1 0.8086409593228309 10.0 0.8086409593228309 0.293909762686134 64.0 0.3410000283729729 0.24053750199604398 25 1.9441497773496836 +KEGG-Module-M00126: Tetrahydrofolate biosynthesis, GTP => THF KEGG-Module-M00126: Tetrahydrofolate biosynthesis, GTP => THF 0.82162710625529 7.5 0.82162710625529 0.676220277743169 14.0 0.6166089596674048 0.21389076133298104 25 0.9585180084927412 +KEGG-Module-M00036: Leucine degradation, leucine => acetoacetate + acetyl-CoA KEGG-Module-M00036: Leucine degradation, leucine => acetoacetate + acetyl-CoA 0.82162710625529 7.5 0.82162710625529 0.330845894691533 60.0 0.4102839356069697 0.27432057191698367 25 1.4994980791043377 +KEGG-Module-M00242: Zinc transport system KEGG-Module-M00242: Zinc transport system 0.82162710625529 7.5 0.82162710625529 0.5074094079519029 33.0 0.51530638465375 0.10667767460938943 25 2.8714604318397714 +KEGG-Module-M00568: Catechol ortho-cleavage, catechol => 3-oxoadipate KEGG-Module-M00568: Catechol ortho-cleavage, catechol => 3-oxoadipate 0.82162710625529 7.5 0.82162710625529 0.756018989487962 8.0 0.7702101668590144 0.15339285144334647 25 0.335197754735433 +KEGG-Module-M00122: Cobalamin biosynthesis, cobinamide => cobalamin KEGG-Module-M00122: Cobalamin biosynthesis, cobinamide => cobalamin 0.8278144449074509 5.0 0.8278144449074509 0.5074094079519029 33.0 0.5351606805944125 0.23498394803170367 25 1.2454202372732033 +KEGG-Pathway-pae00410: beta-Alanine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00410: beta-Alanine metabolism - Pseudomonas aeruginosa PAO1 0.869682302602062 3.5 0.869682302602062 0.790005165289256 5.0 0.7347742099530247 0.1294343404197795 25 1.0422897989166204 +KEGG-Pathway-pae00363: Bisphenol degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00363: Bisphenol degradation - Pseudomonas aeruginosa PAO1 0.869682302602062 3.5 0.869682302602062 0.925907076174786 1.0 0.8701861824926201 0.15493185058259332 25 -0.003252267940151509 +KEGG-Pathway-pae00903: Limonene and pinene degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00903: Limonene and pinene degradation - Pseudomonas aeruginosa PAO1 0.903765587264035 2.0 0.903765587264035 0.8250252159401421 3.0 0.8205113608684794 0.09764290124509128 25 0.8526398266944258 +KEGG-Pathway-pae00040: Pentose and glucuronate interconversions - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00040: Pentose and glucuronate interconversions - Pseudomonas aeruginosa PAO1 0.9235057293279649 1.0 0.9235057293279649 0.6248985923110439 20.0 0.6080508123167512 0.23067034624771687 25 1.367557304797413 diff --git a/pseudomonas_analysis/generic_pathway_summary_E-GEOD-33245_pao1.tsv b/pseudomonas_analysis/generic_pathway_summary_E-GEOD-33245_pao1.tsv new file mode 100644 index 00000000..87a99b09 --- /dev/null +++ b/pseudomonas_analysis/generic_pathway_summary_E-GEOD-33245_pao1.tsv @@ -0,0 +1,170 @@ +pathway Pathway ID Adj P-value (Real) Rank (Real) padj (Real) Median adj p-value (simulated) Rank (simulated) Mean padj (simulated) Std deviation (simulated) Number of experiments (simulated) Z score +KEGG-Module-M00178: Ribosome, bacteria KEGG-Module-M00178: Ribosome, bacteria 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae00020: Citrate cycle (TCA cycle) - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00020: Citrate cycle (TCA cycle) - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae03060: Protein export - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03060: Protein export - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae01210: 2-Oxocarboxylic acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01210: 2-Oxocarboxylic acid metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00193204682641302 149.0 0.002773075039741271 0.0021372293363591433 25 -0.8424707025214595 +KEGG-Pathway-pae00230: Purine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00230: Purine metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129880110667077 154.5 0.0013396583982133196 0.00026585310411691916 25 -1.3809748813861744 +KEGG-Pathway-pae00030: Pentose phosphate pathway - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00030: Pentose phosphate pathway - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00827167644203708 133.0 0.014966891867253586 0.018896824596805015 25 -0.7405672765957925 +KEGG-Pathway-pae00330: Arginine and proline metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00330: Arginine and proline metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.0048090090666894295 142.0 0.013131107777129288 0.01769717633000679 25 -0.687035355873369 +KEGG-Pathway-pae03018: RNA degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03018: RNA degradation - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae03010: Ribosome - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03010: Ribosome - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae00620: Pyruvate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00620: Pyruvate metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00147484902433065 151.0 0.002212294945887818 0.0015271853122728162 25 -0.8118025996160405 +KEGG-Pathway-pae00190: Oxidative phosphorylation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00190: Oxidative phosphorylation - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae00240: Pyrimidine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00240: Pyrimidine metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Module-M00360: Aminoacyl-tRNA biosynthesis, prokaryotes KEGG-Module-M00360: Aminoacyl-tRNA biosynthesis, prokaryotes 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae00400: Phenylalanine, tyrosine and tryptophan biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00400: Phenylalanine, tyrosine and tryptophan biosynthesis - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.0018957239646430698 150.0 0.003958847752667092 0.006460398157237295 25 -0.4622510471792415 +KEGG-Pathway-pae00250: Alanine, aspartate and glutamate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00250: Alanine, aspartate and glutamate metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00199546592358192 148.0 0.003091643737903332 0.0027247852722948516 25 -0.777720659371176 +KEGG-Pathway-pae00680: Methane metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00680: Methane metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.0015453494782659966 0.0007750179088834073 25 -0.7391152287073939 +KEGG-Pathway-pae00540: Lipopolysaccharide biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00540: Lipopolysaccharide biosynthesis - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00628798214064244 138.0 0.007581234598906049 0.007353606313936736 25 -0.8987036261503071 +KEGG-Pathway-pae00010: Glycolysis / Gluconeogenesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00010: Glycolysis / Gluconeogenesis - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00137519122481529 152.0 0.0015209771128703992 0.00045216330472069334 25 -1.212958167668815 +KEGG-Module-M00335: Sec (secretion) system KEGG-Module-M00335: Sec (secretion) system 0.0009725219392893109 157.0 0.0009725219392893109 0.00129880110667077 154.5 0.0015695348756376204 0.001226937853901353 25 -0.48658775540257304 +KEGG-Module-M00144: NADH:quinone oxidoreductase, prokaryotes KEGG-Module-M00144: NADH:quinone oxidoreductase, prokaryotes 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.0054394114698376565 0.017143694053417306 25 -0.2605558356693811 +KEGG-Module-M00009: Citrate cycle (TCA cycle, Krebs cycle) KEGG-Module-M00009: Citrate cycle (TCA cycle, Krebs cycle) 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00970: Aminoacyl-tRNA biosynthesis - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.001283494787822031 0.00016709507331584875 25 -1.861053365379054 +KEGG-Pathway-pae00270: Cysteine and methionine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00270: Cysteine and methionine metabolism - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.00514242462278109 139.0 0.012854477134522375 0.01896549973790223 25 -0.6265036703191733 +KEGG-Module-M00011: Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate KEGG-Module-M00011: Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate 0.0009725219392893109 157.0 0.0009725219392893109 0.00129007633587786 162.5 0.0013139330310959565 0.0002326587468478468 25 -1.467432866514665 +KEGG-Pathway-pae02040: Flagellar assembly - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae02040: Flagellar assembly - Pseudomonas aeruginosa PAO1 0.0009725219392893109 157.0 0.0009725219392893109 0.0013315474314528801 153.0 0.00163113598380972 0.000819166880606729 25 -0.8040047273793542 +KEGG-Module-M00157: F-type ATPase, prokaryotes and chloroplasts KEGG-Module-M00157: F-type ATPase, prokaryotes and chloroplasts 0.000983061101028433 144.0 0.000983061101028433 0.00129007633587786 162.5 0.0012874527214643964 0.000166323013658901 25 -1.8301232868484252 +KEGG-Module-M00002: Glycolysis, core module involving three-carbon compounds KEGG-Module-M00002: Glycolysis, core module involving three-carbon compounds 0.00189330286123995 143.0 0.00189330286123995 0.00309917355371901 144.0 0.004585314303241495 0.004248466379324902 25 -0.6336431082760073 +KEGG-Pathway-pae02030: Bacterial chemotaxis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae02030: Bacterial chemotaxis - Pseudomonas aeruginosa PAO1 0.0026192413499167 141.0 0.0026192413499167 0.0020670254403131103 147.0 0.0026078203904893655 0.0018457175058843116 25 0.006187815519397336 +KEGG-Module-M00156: Cytochrome c oxidase, cbb3-type KEGG-Module-M00156: Cytochrome c oxidase, cbb3-type 0.0026192413499167 141.0 0.0026192413499167 0.00308636338732947 145.0 0.007567277555178355 0.01142994362234345 25 -0.4329011908325733 +KEGG-Pathway-pae00630: Glyoxylate and dicarboxylate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00630: Glyoxylate and dicarboxylate metabolism - Pseudomonas aeruginosa PAO1 0.0026192413499167 141.0 0.0026192413499167 0.0259777581736039 121.0 0.03836597088374069 0.040254324138615086 25 -0.8880221019419113 +KEGG-Module-M00506: CheA-CheYBV (chemotaxis) two-component regulatory system KEGG-Module-M00506: CheA-CheYBV (chemotaxis) two-component regulatory system 0.00337195788045511 139.0 0.00337195788045511 0.00374947307700841 143.0 0.006007952156219429 0.006984145983576902 25 -0.3774254263818102 +KEGG-Module-M00010: Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate KEGG-Module-M00010: Citrate cycle, first carbon oxidation, oxaloacetate => 2-oxoglutarate 0.00414150721455458 138.0 0.00414150721455458 0.00247760625119116 146.0 0.0029674124957757347 0.0016468558994550137 25 0.7129310580041537 +KEGG-Module-M00048: Inosine monophosphate biosynthesis, PRPP + glutamine => IMP KEGG-Module-M00048: Inosine monophosphate biosynthesis, PRPP + glutamine => IMP 0.00502501890222664 137.0 0.00502501890222664 0.0429743659960683 112.0 0.09868949469453701 0.11597889868364489 25 -0.8075992862098005 +KEGG-Pathway-pae03030: DNA replication - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03030: DNA replication - Pseudomonas aeruginosa PAO1 0.0068108909773830105 136.0 0.0068108909773830105 0.00793799906059183 135.0 0.011001537073475008 0.009746289163259543 25 -0.429973503340063 +KEGG-Module-M00125: Riboflavin biosynthesis, GTP => riboflavin/FMN/FAD KEGG-Module-M00125: Riboflavin biosynthesis, GTP => riboflavin/FMN/FAD 0.00681573758738125 135.0 0.00681573758738125 0.0202198868229588 125.0 0.026836670901645703 0.018756309695265018 25 -1.0674239037180477 +KEGG-Module-M00436: Sulfonate transport system KEGG-Module-M00436: Sulfonate transport system 0.00793248469828396 134.0 0.00793248469828396 0.004891556035813521 141.0 0.010936922849084485 0.015072666125562439 25 -0.1993302396385705 +KEGG-Pathway-pae00260: Glycine, serine and threonine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00260: Glycine, serine and threonine metabolism - Pseudomonas aeruginosa PAO1 0.008400124262193229 133.0 0.008400124262193229 0.0336117740652347 119.0 0.04690629159254252 0.05031623807702084 25 -0.7652831134037991 +KEGG-Module-M00188: NitT/TauT family transport system KEGG-Module-M00188: NitT/TauT family transport system 0.00906555090655509 131.5 0.00906555090655509 0.00630185513191013 137.0 0.013929613353681649 0.01845689350312174 25 -0.2635363554708633 +KEGG-Pathway-pae03440: Homologous recombination - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03440: Homologous recombination - Pseudomonas aeruginosa PAO1 0.00906555090655509 131.5 0.00906555090655509 0.0191986717350461 126.0 0.02376574282584565 0.018493491820768905 25 -0.7948846038248807 +KEGG-Module-M00331: Type II general secretion pathway KEGG-Module-M00331: Type II general secretion pathway 0.00938367573570239 130.0 0.00938367573570239 0.0481430046647438 111.0 0.09362369604588232 0.18139590787171597 25 -0.46439868075609986 +KEGG-Module-M00034: Methionine salvage pathway KEGG-Module-M00034: Methionine salvage pathway 0.00994933561432732 129.0 0.00994933561432732 0.0761307282332499 100.0 0.13863650648976114 0.11530568940966236 25 -1.1160522220046682 +KEGG-Pathway-pae00550: Peptidoglycan biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00550: Peptidoglycan biosynthesis - Pseudomonas aeruginosa PAO1 0.0116247803548091 127.5 0.0116247803548091 0.0145844253806717 129.0 0.020471053408149368 0.01994803527521205 25 -0.4434658817920218 +KEGG-Pathway-pae00300: Lysine biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00300: Lysine biosynthesis - Pseudomonas aeruginosa PAO1 0.0116247803548091 127.5 0.0116247803548091 0.00923893388506211 131.0 0.015787248996230505 0.01684949757150071 25 -0.24703814601936955 +KEGG-Pathway-pae00520: Amino sugar and nucleotide sugar metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00520: Amino sugar and nucleotide sugar metabolism - Pseudomonas aeruginosa PAO1 0.0117877151083633 126.0 0.0117877151083633 0.0839392307957242 97.0 0.10790361272423384 0.10058177399464603 25 -0.9555995465041887 +KEGG-Pathway-pae00523: Polyketide sugar unit biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00523: Polyketide sugar unit biosynthesis - Pseudomonas aeruginosa PAO1 0.0132049590220864 124.5 0.0132049590220864 0.00496641060754777 140.0 0.006246897118008498 0.004375884644090909 25 1.5900926258359902 +KEGG-Pathway-pae00760: Nicotinate and nicotinamide metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00760: Nicotinate and nicotinamide metabolism - Pseudomonas aeruginosa PAO1 0.0132049590220864 124.5 0.0132049590220864 0.00805682684973303 134.0 0.00857102800587275 0.005092773158759346 25 0.9099032828987271 +KEGG-Module-M00115: NAD biosynthesis, aspartate => NAD KEGG-Module-M00115: NAD biosynthesis, aspartate => NAD 0.0140025754243754 123.0 0.0140025754243754 0.0120014202864244 130.0 0.015264020573739118 0.012855240491267966 25 -0.09812691954075592 +KEGG-Module-M00018: Threonine biosynthesis, aspartate => homoserine => threonine KEGG-Module-M00018: Threonine biosynthesis, aspartate => homoserine => threonine 0.0146051519729598 121.5 0.0146051519729598 0.0821462855097458 98.0 0.09542525015219988 0.06886044776298038 25 -1.1736795330960548 +KEGG-Module-M00050: Guanine ribonucleotide biosynthesis IMP => GDP,GTP KEGG-Module-M00050: Guanine ribonucleotide biosynthesis IMP => GDP,GTP 0.0146051519729598 121.5 0.0146051519729598 0.0148717110638993 128.0 0.022648941696211854 0.015427157669638352 25 -0.5214045189336954 +KEGG-Module-M00119: Pantothenate biosynthesis, valine/L-aspartate => pantothenate KEGG-Module-M00119: Pantothenate biosynthesis, valine/L-aspartate => pantothenate 0.0146342972011752 120.0 0.0146342972011752 0.0581160524978535 105.0 0.06334845813520475 0.029793206923242468 25 -1.6350761117973622 +KEGG-Pathway-pae00640: Propanoate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00640: Propanoate metabolism - Pseudomonas aeruginosa PAO1 0.0149995912599703 119.0 0.0149995912599703 0.0352750865352838 117.0 0.04788299874789683 0.04147368139691437 25 -0.7928740922037619 +KEGG-Pathway-pae00770: Pantothenate and CoA biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00770: Pantothenate and CoA biosynthesis - Pseudomonas aeruginosa PAO1 0.0170068027210884 118.0 0.0170068027210884 0.0232302405498282 123.0 0.03484630252840033 0.024881552257555915 25 -0.7169769644052058 +KEGG-Pathway-pae03430: Mismatch repair - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03430: Mismatch repair - Pseudomonas aeruginosa PAO1 0.0174036007796331 117.0 0.0174036007796331 0.0553266467877474 107.0 0.0680280457264055 0.04527370805285482 25 -1.1181864071675078 +KEGG-Pathway-pae00364: Fluorobenzoate degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00364: Fluorobenzoate degradation - Pseudomonas aeruginosa PAO1 0.0185918591859186 116.0 0.0185918591859186 0.0210351741213198 124.0 0.025487392101618243 0.022796007977564394 25 -0.3024886165369901 +KEGG-Module-M00332: Type III secretion system KEGG-Module-M00332: Type III secretion system 0.0234465133260314 115.0 0.0234465133260314 0.00837545842006145 132.0 0.019894952502856045 0.03459784778473139 25 0.10265265184335298 +KEGG-Pathway-pae01220: Degradation of aromatic compounds - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01220: Degradation of aromatic compounds - Pseudomonas aeruginosa PAO1 0.0291468993111939 113.5 0.0291468993111939 0.0064720374790967206 136.0 0.012940638762258634 0.016770955672949398 25 0.9663289835697941 +KEGG-Pathway-pae00521: Streptomycin biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00521: Streptomycin biosynthesis - Pseudomonas aeruginosa PAO1 0.0291468993111939 113.5 0.0291468993111939 0.0164312665238186 127.0 0.018811638611416888 0.013008947776507032 25 0.7944732254549862 +KEGG-Module-M00008: Entner-Doudoroff pathway, glucose-6P => glyceraldehyde-3P + pyruvate KEGG-Module-M00008: Entner-Doudoroff pathway, glucose-6P => glyceraldehyde-3P + pyruvate 0.0301615973694458 112.0 0.0301615973694458 0.0743328723331897 101.0 0.08378933351912457 0.04606771774863636 25 -1.1641066406261507 +KEGG-Pathway-pae00450: Selenocompound metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00450: Selenocompound metabolism - Pseudomonas aeruginosa PAO1 0.0337818731412413 110.5 0.0337818731412413 0.03890608875129 114.0 0.04964013482565779 0.034047221096433364 25 -0.465772570381015 +KEGG-Pathway-pae00900: Terpenoid backbone biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00900: Terpenoid backbone biosynthesis - Pseudomonas aeruginosa PAO1 0.0337818731412413 110.5 0.0337818731412413 0.0505585977139137 110.0 0.06391184175785028 0.04641852449267984 25 -0.649093631172194 +KEGG-Module-M00210: Putative ABC transport system KEGG-Module-M00210: Putative ABC transport system 0.0338983432835485 108.0 0.0338983432835485 0.0356190091234554 116.0 0.04959121469680122 0.04191671475560846 25 -0.374382188698436 +KEGG-Module-M00616: Sulfate-sulfur assimilation KEGG-Module-M00616: Sulfate-sulfur assimilation 0.0338983432835485 108.0 0.0338983432835485 0.131430626170725 88.0 0.17693987063742342 0.1606278885246481 25 -0.8905148954375095 +KEGG-Pathway-pae00440: Phosphonate and phosphinate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00440: Phosphonate and phosphinate metabolism - Pseudomonas aeruginosa PAO1 0.0338983432835485 108.0 0.0338983432835485 0.026850969176993998 120.0 0.029234072611113757 0.013296758368885777 25 0.3507825398518989 +KEGG-Module-M00240: Iron complex transport system KEGG-Module-M00240: Iron complex transport system 0.0358757898894155 106.0 0.0358757898894155 0.0559758104151976 106.0 0.1068608757332872 0.14931175479916303 25 -0.4754152540726124 +KEGG-Module-M00016: Lysine biosynthesis, succinyl-DAP pathway, aspartate => lysine KEGG-Module-M00016: Lysine biosynthesis, succinyl-DAP pathway, aspartate => lysine 0.0407884151246983 104.5 0.0407884151246983 0.06569464881377599 103.0 0.08408846774701167 0.07259743607401058 25 -0.5964405213728273 +KEGG-Module-M00452: CusS-CusR (copper tolerance) two-component regulatory system KEGG-Module-M00452: CusS-CusR (copper tolerance) two-component regulatory system 0.0407884151246983 104.5 0.0407884151246983 0.0911653329522721 94.0 0.09644648897802632 0.048773726465325545 25 -1.1411486857149766 +KEGG-Pathway-pae00670: One carbon pool by folate - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00670: One carbon pool by folate - Pseudomonas aeruginosa PAO1 0.0409653012890818 103.0 0.0409653012890818 0.0534465852271026 109.0 0.07375201742001337 0.05653991730452598 25 -0.5798861705853082 +KEGG-Pathway-pae00480: Glutathione metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00480: Glutathione metabolism - Pseudomonas aeruginosa PAO1 0.0412860336684384 102.0 0.0412860336684384 0.0386621982161851 115.0 0.06753344957502053 0.06255164585090286 25 -0.41961191507486567 +KEGG-Pathway-pae00650: Butanoate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00650: Butanoate metabolism - Pseudomonas aeruginosa PAO1 0.0415278055073488 101.0 0.0415278055073488 0.120671414418961 91.0 0.13665983015921904 0.09848073608950168 25 -0.9659962793678952 +KEGG-Module-M00529: Denitrification, nitrate => nitrogen KEGG-Module-M00529: Denitrification, nitrate => nitrogen 0.0416682337700328 100.0 0.0416682337700328 0.6194060128097011 28.5 0.5627927122280212 0.29267446509620854 25 -1.7805601123647166 +KEGG-Module-M00024: Phenylalanine biosynthesis, chorismate => phenylalanine KEGG-Module-M00024: Phenylalanine biosynthesis, chorismate => phenylalanine 0.0424843397558807 99.0 0.0424843397558807 0.0658825223721979 102.0 0.06550547231128057 0.027349888341789873 25 -0.841726747389466 +KEGG-Module-M00258: Putative ABC transport system KEGG-Module-M00258: Putative ABC transport system 0.0484677155031137 98.0 0.0484677155031137 0.0807890034795147 99.0 0.09857124641462094 0.05916145533194595 25 -0.8468948343204866 +KEGG-Module-M00053: Pyrimidine deoxyribonuleotide biosynthesis, CDP/CTP => dCDP/dCTP,dTDP/dTTP KEGG-Module-M00053: Pyrimidine deoxyribonuleotide biosynthesis, CDP/CTP => dCDP/dCTP,dTDP/dTTP 0.0493954456976883 97.0 0.0493954456976883 0.0548951936253362 108.0 0.07252050145408058 0.045745268037772 25 -0.5055179857575183 +KEGG-Module-M00082: Fatty acid biosynthesis, initiation KEGG-Module-M00082: Fatty acid biosynthesis, initiation 0.0549185755628587 96.0 0.0549185755628587 0.363277738023156 55.0 0.368499717722318 0.12533507931434582 25 -2.5019423442736586 +KEGG-Module-M00176: Assimilatory sulfate reduction, sulfate => H2S KEGG-Module-M00176: Assimilatory sulfate reduction, sulfate => H2S 0.0582233529442943 94.5 0.0582233529442943 0.0991206717115592 93.0 0.11602677940669695 0.08108768954130702 25 -0.7128508259315602 +KEGG-Pathway-pae00460: Cyanoamino acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00460: Cyanoamino acid metabolism - Pseudomonas aeruginosa PAO1 0.0582233529442943 94.5 0.0582233529442943 0.23429705315114102 73.0 0.26217136357614457 0.16601120404327668 25 -1.228519555696277 +KEGG-Module-M00083: Fatty acid biosynthesis, elongation KEGG-Module-M00083: Fatty acid biosynthesis, elongation 0.0607864842874254 93.0 0.0607864842874254 0.18064707531024 82.0 0.1938919034440162 0.08825826490786429 25 -1.5081354623903374 +KEGG-Module-M00019: Valine/isoleucine biosynthesis, pyruvate => valine / 2-oxobutanoate => isoleucine KEGG-Module-M00019: Valine/isoleucine biosynthesis, pyruvate => valine / 2-oxobutanoate => isoleucine 0.0629229021583445 92.0 0.0629229021583445 0.0352307062466878 118.0 0.04025305140903666 0.028972354800626026 25 0.7824649016385093 +KEGG-Pathway-pae00401: Novobiocin biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00401: Novobiocin biosynthesis - Pseudomonas aeruginosa PAO1 0.0683807203872847 91.0 0.0683807203872847 0.21659312841617004 75.0 0.1949079015507873 0.08406414373415068 25 -1.5051266276337683 +KEGG-Module-M00049: Adenine ribonucleotide biosynthesis, IMP => ADP,ATP KEGG-Module-M00049: Adenine ribonucleotide biosynthesis, IMP => ADP,ATP 0.0696498790078645 90.0 0.0696498790078645 0.12667070613277498 89.0 0.16726834029963547 0.11311649893122655 25 -0.862990476315235 +KEGG-Pathway-pae00061: Fatty acid biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00061: Fatty acid biosynthesis - Pseudomonas aeruginosa PAO1 0.0768680961663418 89.0 0.0768680961663418 0.20201650472514301 78.5 0.22922940717152548 0.11328383602364332 25 -1.3449519044657399 +KEGG-Pathway-pae00750: Vitamin B6 metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00750: Vitamin B6 metabolism - Pseudomonas aeruginosa PAO1 0.0809243645851779 88.0 0.0809243645851779 0.120191235351116 92.0 0.12588942582685614 0.07335045380300025 25 -0.6130168105359293 +KEGG-Module-M00533: Homoprotocatechuate degradation, homoprotocatechuate => 2-oxohept-3-enedioate KEGG-Module-M00533: Homoprotocatechuate degradation, homoprotocatechuate => 2-oxohept-3-enedioate 0.0853541025658065 87.0 0.0853541025658065 0.0651483962723156 104.0 0.09618262771134076 0.13253906841281313 25 -0.08170062816351753 +KEGG-Module-M00023: Tryptophan biosynthesis, chorismate => tryptophan KEGG-Module-M00023: Tryptophan biosynthesis, chorismate => tryptophan 0.10075919536580401 86.0 0.10075919536580401 0.0245592974031718 122.0 0.04858988708230525 0.05345132273647673 25 0.9760152904110811 +KEGG-Pathway-pae00627: Aminobenzoate degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00627: Aminobenzoate degradation - Pseudomonas aeruginosa PAO1 0.10442926452485 85.0 0.10442926452485 0.179366792588595 83.0 0.19353623167032308 0.14396461009626216 25 -0.6189504982223865 +KEGG-Pathway-pae00910: Nitrogen metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00910: Nitrogen metabolism - Pseudomonas aeruginosa PAO1 0.104572766114717 84.0 0.104572766114717 0.632787654356359 24.5 0.5383591192202831 0.2318139387583763 25 -1.8712694992759222 +KEGG-Pathway-pae00281: Geraniol degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00281: Geraniol degradation - Pseudomonas aeruginosa PAO1 0.13577290842929401 83.0 0.13577290842929401 0.372652465089769 53.0 0.40020049197913893 0.25730411720325175 25 -1.0276850072358779 +KEGG-Module-M00087: beta-Oxidation KEGG-Module-M00087: beta-Oxidation 0.139914772727273 82.0 0.139914772727273 0.542134210526316 39.0 0.5075860288549506 0.14645152050242713 25 -2.5105321874864672 +KEGG-Pathway-pae00362: Benzoate degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00362: Benzoate degradation - Pseudomonas aeruginosa PAO1 0.14179339276350303 80.5 0.14179339276350303 0.392159431928653 52.0 0.40880849616601034 0.16181703861853522 25 -1.6501049931581326 +KEGG-Module-M00324: Dipeptide transport system KEGG-Module-M00324: Dipeptide transport system 0.14179339276350303 80.5 0.14179339276350303 0.150632276753384 86.0 0.15681716427860168 0.11968513583210842 25 -0.12552746346190938 +KEGG-Pathway-pae00310: Lysine degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00310: Lysine degradation - Pseudomonas aeruginosa PAO1 0.14413129469039998 79.0 0.14413129469039998 0.15483253325830101 85.0 0.16932306447955867 0.10576810401246615 25 -0.2381792698693881 +KEGG-Pathway-pae00290: Valine, leucine and isoleucine biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00290: Valine, leucine and isoleucine biosynthesis - Pseudomonas aeruginosa PAO1 0.16324200913242 77.5 0.16324200913242 0.126557632398754 90.0 0.14240598479449976 0.08575610663920362 25 0.2429684037031016 +KEGG-Pathway-pae00740: Riboflavin metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00740: Riboflavin metabolism - Pseudomonas aeruginosa PAO1 0.16324200913242 77.5 0.16324200913242 0.20201650472514301 78.5 0.23013338225272634 0.1157221153785193 25 -0.5780344828774441 +KEGG-Module-M00193: Putative spermidine/putrescine transport system KEGG-Module-M00193: Putative spermidine/putrescine transport system 0.164966205563401 75.5 0.164966205563401 0.28867300096082 64.0 0.3250285336465613 0.1827871174789531 25 -0.8756761980317929 +KEGG-Module-M00200: Putative sorbitol/mannitol transport system KEGG-Module-M00200: Putative sorbitol/mannitol transport system 0.164966205563401 75.5 0.164966205563401 0.150050735667174 87.0 0.15264309046733301 0.046121659082265926 25 0.26718715981330127 +KEGG-Pathway-pae00500: Starch and sucrose metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00500: Starch and sucrose metabolism - Pseudomonas aeruginosa PAO1 0.16967871485943803 74.0 0.16967871485943803 0.20822722469958302 77.0 0.2509325535847064 0.208007167779536 25 -0.3906299941134154 +KEGG-Module-M00260: DNA polymerase III complex, bacteria KEGG-Module-M00260: DNA polymerase III complex, bacteria 0.172329597545232 73.0 0.172329597545232 0.18383195718412998 81.0 0.18093572834656058 0.046161804991834844 25 -0.18643401840224488 +KEGG-Pathway-pae00340: Histidine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00340: Histidine metabolism - Pseudomonas aeruginosa PAO1 0.179445821589867 72.0 0.179445821589867 0.21220902153965 76.0 0.2494287519401428 0.14887694667078902 25 -0.4700723108261266 +KEGG-Pathway-pae01053: Biosynthesis of siderophore group nonribosomal peptides - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01053: Biosynthesis of siderophore group nonribosomal peptides - Pseudomonas aeruginosa PAO1 0.188785260213832 71.0 0.188785260213832 0.42562962962963 51.0 0.3816812159948046 0.20863183857273312 25 -0.9245758322439617 +KEGG-Module-M00570: Isoleucine biosynthesis, threonine => 2-oxobutanoate => isoleucine KEGG-Module-M00570: Isoleucine biosynthesis, threonine => 2-oxobutanoate => isoleucine 0.211309223437062 70.0 0.211309223437062 0.25216332748466397 70.0 0.24935349013385733 0.0853701783230282 25 -0.4456388336550197 +KEGG-Pathway-pae00930: Caprolactam degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00930: Caprolactam degradation - Pseudomonas aeruginosa PAO1 0.221621542685242 69.0 0.221621542685242 0.6206304234083929 26.0 0.5970747325859435 0.22681819300332842 25 -1.6553045632243084 +KEGG-Module-M00299: Spermidine/putrescine transport system KEGG-Module-M00299: Spermidine/putrescine transport system 0.224492110126871 66.5 0.224492110126871 0.0887476459510358 96.0 0.1147728884872223 0.10860347385148453 25 1.0102735920739512 +KEGG-Module-M00185: Sulfate transport system KEGG-Module-M00185: Sulfate transport system 0.224492110126871 66.5 0.224492110126871 0.52499667891777 41.0 0.546212668849196 0.16600582661237318 25 -1.9380076307414722 +KEGG-Pathway-pae04122: Sulfur relay system - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae04122: Sulfur relay system - Pseudomonas aeruginosa PAO1 0.224492110126871 66.5 0.224492110126871 0.0389163695932888 113.0 0.06313014143364329 0.06567758052375769 25 2.456880527668919 +KEGG-Module-M00124: Pyridoxal biosynthesis, erythrose-4P => pyridoxal-5P KEGG-Module-M00124: Pyridoxal biosynthesis, erythrose-4P => pyridoxal-5P 0.224492110126871 66.5 0.224492110126871 0.16798932509305403 84.0 0.17166966942834677 0.06735307730748889 25 0.7842617265633234 +KEGG-Pathway-pae00730: Thiamine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00730: Thiamine metabolism - Pseudomonas aeruginosa PAO1 0.22596388684212698 64.0 0.22596388684212698 0.0902604200046999 95.0 0.11961889913510197 0.06198760106241677 25 1.715584824777196 +KEGG-Module-M00230: Glutamate/aspartate transport system KEGG-Module-M00230: Glutamate/aspartate transport system 0.22988106593311605 63.0 0.22988106593311605 0.5865524215057349 33.0 0.5460686342722285 0.18723038359625263 25 -1.6887620602270712 +KEGG-Pathway-pae03410: Base excision repair - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03410: Base excision repair - Pseudomonas aeruginosa PAO1 0.27133265732546696 62.0 0.27133265732546696 0.654063709437332 21.0 0.6320283048319076 0.22349808777315125 25 -1.6138645797835365 +KEGG-Module-M00300: Putrescine transport system KEGG-Module-M00300: Putrescine transport system 0.27646564211858304 61.0 0.27646564211858304 0.28548647402397803 65.0 0.3326343547160293 0.16034674737292057 25 -0.3502953038817429 +KEGG-Pathway-pae00350: Tyrosine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00350: Tyrosine metabolism - Pseudomonas aeruginosa PAO1 0.279391574949088 60.0 0.279391574949088 0.6782301804167821 18.0 0.6141276685053577 0.22466188764228534 25 -1.4899549588457497 +KEGG-Pathway-pae00361: Chlorocyclohexane and chlorobenzene degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00361: Chlorocyclohexane and chlorobenzene degradation - Pseudomonas aeruginosa PAO1 0.28197799257971196 59.0 0.28197799257971196 0.592972626507089 31.0 0.557161816020065 0.15478344449968623 25 -1.7778634163998777 +KEGG-Module-M00432: Leucine biosynthesis, 2-oxoisovalerate => 2-oxoisocaproate KEGG-Module-M00432: Leucine biosynthesis, 2-oxoisovalerate => 2-oxoisocaproate 0.282675196009936 57.0 0.282675196009936 0.242809741745669 72.0 0.27293238756419547 0.11763108834267147 25 0.08282511522259102 +KEGG-Pathway-pae03420: Nucleotide excision repair - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03420: Nucleotide excision repair - Pseudomonas aeruginosa PAO1 0.282675196009936 57.0 0.282675196009936 0.312740035022111 62.0 0.33493298861100507 0.1059088749459215 25 -0.4934222238481203 +KEGG-Pathway-pae00660: C5-Branched dibasic acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00660: C5-Branched dibasic acid metabolism - Pseudomonas aeruginosa PAO1 0.282675196009936 57.0 0.282675196009936 0.36111111111111105 56.0 0.36651197643603406 0.11304765505492156 25 -0.7416056563523401 +KEGG-Pathway-pae00590: Arachidonic acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00590: Arachidonic acid metabolism - Pseudomonas aeruginosa PAO1 0.30045684199925 54.5 0.30045684199925 0.43177149130419 50.0 0.44219504158506284 0.13116776920149398 25 -1.0805871019128264 +KEGG-Pathway-pae00471: D-Glutamine and D-glutamate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00471: D-Glutamine and D-glutamate metabolism - Pseudomonas aeruginosa PAO1 0.30045684199925 54.5 0.30045684199925 0.34167206273832695 57.0 0.3424389526066714 0.0785390565760186 25 -0.5345380048815149 +KEGG-Module-M00647: Multidrug resistance, efflux pump MexAB-OprM/SmeDEF/AcrAB-TolC KEGG-Module-M00647: Multidrug resistance, efflux pump MexAB-OprM/SmeDEF/AcrAB-TolC 0.334022316327217 53.0 0.334022316327217 0.28505265119746503 66.0 0.3005532831460217 0.10401753488193033 25 0.3217633759460442 +KEGG-Pathway-pae00051: Fructose and mannose metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00051: Fructose and mannose metabolism - Pseudomonas aeruginosa PAO1 0.34851807729102396 52.0 0.34851807729102396 0.653504054488471 22.0 0.6164247217881947 0.1475460106433502 25 -1.8157498351125032 +KEGG-Module-M00307: Pyruvate oxidation, pyruvate => acetyl-CoA KEGG-Module-M00307: Pyruvate oxidation, pyruvate => acetyl-CoA 0.35165734018955397 50.5 0.35165734018955397 0.326396279216428 60.0 0.30377079040951743 0.10218791473497665 25 0.4686126525257887 +KEGG-Module-M00028: Ornithine biosynthesis, glutamate => ornithine KEGG-Module-M00028: Ornithine biosynthesis, glutamate => ornithine 0.35165734018955397 50.5 0.35165734018955397 0.521604938271605 42.0 0.5240134785834062 0.1274847383914722 25 -1.3519746800169266 +KEGG-Module-M00349: Microcin C transport system KEGG-Module-M00349: Microcin C transport system 0.3571141938466071 49.0 0.3571141938466071 0.192097976206755 80.0 0.20245127230049548 0.09524792459455668 25 1.623793087402877 +KEGG-Pathway-pae02060: Phosphotransferase system (PTS) - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae02060: Phosphotransferase system (PTS) - Pseudomonas aeruginosa PAO1 0.371642202548912 47.5 0.371642202548912 0.47781337047353795 44.0 0.4637966948843559 0.05485388876918457 25 -1.679999256264467 +KEGG-Pathway-pae00052: Galactose metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00052: Galactose metabolism - Pseudomonas aeruginosa PAO1 0.371642202548912 47.5 0.371642202548912 0.328037197046297 59.0 0.32649421563207154 0.10599283240838288 25 0.42595320731583497 +KEGG-Pathway-pae00561: Glycerolipid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00561: Glycerolipid metabolism - Pseudomonas aeruginosa PAO1 0.38064347415305705 46.0 0.38064347415305705 0.513626603956853 43.0 0.5361096906220313 0.20901410088051772 25 -0.7438073116313144 +KEGG-Pathway-pae00625: Chloroalkane and chloroalkene degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00625: Chloroalkane and chloroalkene degradation - Pseudomonas aeruginosa PAO1 0.43743054526596503 43.5 0.43743054526596503 0.43766990675863704 49.0 0.46056111692007407 0.17496739736420758 25 -0.13219932400298004 +KEGG-Module-M00021: Cysteine biosynthesis, serine => cysteine KEGG-Module-M00021: Cysteine biosynthesis, serine => cysteine 0.43743054526596503 43.5 0.43743054526596503 0.257875546035452 68.0 0.2724998999299056 0.07671812592198102 25 2.1498263070683805 +KEGG-Pathway-pae00430: Taurine and hypotaurine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00430: Taurine and hypotaurine metabolism - Pseudomonas aeruginosa PAO1 0.43743054526596503 43.5 0.43743054526596503 0.8226559147207031 4.0 0.8210930906103924 0.09123087984282194 25 -4.205402227901609 +KEGG-Module-M00222: Phosphate transport system KEGG-Module-M00222: Phosphate transport system 0.43743054526596503 43.5 0.43743054526596503 0.6194060128097011 28.5 0.5776129739008526 0.226195117292153 25 -0.6197411788240698 +KEGG-Pathway-pae00312: beta-Lactam resistance - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00312: beta-Lactam resistance - Pseudomonas aeruginosa PAO1 0.45076163327265295 41.0 0.45076163327265295 0.564348348348348 34.0 0.5340663522020037 0.1003199558134824 25 -0.830390307230928 +KEGG-Pathway-pae00130: Ubiquinone and other terpenoid-quinone biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00130: Ubiquinone and other terpenoid-quinone biosynthesis - Pseudomonas aeruginosa PAO1 0.466902654867257 40.0 0.466902654867257 0.25725110863458 69.0 0.28239409363867546 0.16236436130770068 25 1.136385840725939 +KEGG-Module-M00323: Urea transport system KEGG-Module-M00323: Urea transport system 0.467052531211823 38.5 0.467052531211823 0.3006757944628449 63.0 0.3511268023416769 0.2154023810136812 25 0.538182207293164 +KEGG-Module-M00254: ABC-2 type transport system KEGG-Module-M00254: ABC-2 type transport system 0.467052531211823 38.5 0.467052531211823 0.28222111877612105 67.0 0.27786635796564474 0.10571880481619403 25 1.7895224371397611 +KEGG-Module-M00328: Hemophore/metalloprotease transport system KEGG-Module-M00328: Hemophore/metalloprotease transport system 0.470765352697875 36.5 0.470765352697875 0.6835637242747329 17.0 0.6279555325818563 0.22338762232739748 25 -0.70366557576589 +KEGG-Pathway-pae00380: Tryptophan metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00380: Tryptophan metabolism - Pseudomonas aeruginosa PAO1 0.470765352697875 36.5 0.470765352697875 0.632787654356359 24.5 0.5901814201552757 0.21161552582474136 25 -0.5643067397441357 +KEGG-Pathway-pae01212: Fatty acid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01212: Fatty acid metabolism - Pseudomonas aeruginosa PAO1 0.470836274648219 35.0 0.470836274648219 0.554914037026676 37.0 0.5737961727877442 0.14492176647248997 25 -0.710451581192048 +KEGG-Pathway-pae00071: Fatty acid degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00071: Fatty acid degradation - Pseudomonas aeruginosa PAO1 0.49344336333671396 34.0 0.49344336333671396 0.669756267733792 20.0 0.6627564187552352 0.11628049252858773 25 -1.4560744604422393 +KEGG-Module-M00190: Iron(III) transport system KEGG-Module-M00190: Iron(III) transport system 0.49639300227043703 33.0 0.49639300227043703 0.4761107434546071 46.0 0.46796629250535865 0.12142073447161063 25 0.2341174255680757 +KEGG-Module-M00572: Pimeloyl-ACP biosynthesis, BioC-BioH pathway, malonyl-ACP => pimeloyl-ACP KEGG-Module-M00572: Pimeloyl-ACP biosynthesis, BioC-BioH pathway, malonyl-ACP => pimeloyl-ACP 0.588059510067975 32.0 0.588059510067975 0.545344338884174 38.0 0.5317820140757471 0.09876302735161867 25 0.5698235210213562 +KEGG-Module-M00235: Arginine/ornithine transport system KEGG-Module-M00235: Arginine/ornithine transport system 0.5995825004631851 30.0 0.5995825004631851 0.619456547607133 27.0 0.6126137869255704 0.13214182392493035 25 -0.09861591186896622 +KEGG-Pathway-pae00920: Sulfur metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00920: Sulfur metabolism - Pseudomonas aeruginosa PAO1 0.5995825004631851 30.0 0.5995825004631851 0.230711293131855 74.0 0.4193184660258587 0.3553878214409409 25 0.5072318846111136 +KEGG-Module-M00334: Type VI secretion system KEGG-Module-M00334: Type VI secretion system 0.5995825004631851 30.0 0.5995825004631851 0.4493125 48.0 0.48174288688635913 0.2429340512945413 25 0.48506832594642435 +KEGG-Pathway-pae00790: Folate biosynthesis - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00790: Folate biosynthesis - Pseudomonas aeruginosa PAO1 0.611539368222537 27.0 0.611539368222537 0.6122582029444771 30.0 0.588596551086331 0.20708095094205667 25 0.1107915384386349 +KEGG-Module-M00223: Phosphonate transport system KEGG-Module-M00223: Phosphonate transport system 0.611539368222537 27.0 0.611539368222537 0.712107234708711 14.0 0.719784948116279 0.1266908628977136 25 -0.8544071562693222 +KEGG-Module-M00045: Histidine degradation, histidine => N-formiminoglutamate => glutamate KEGG-Module-M00045: Histidine degradation, histidine => N-formiminoglutamate => glutamate 0.611539368222537 27.0 0.611539368222537 0.754544284706888 10.0 0.739193607200058 0.16155794662639802 25 -0.7901452181285817 +KEGG-Module-M00238: D-Methionine transport system KEGG-Module-M00238: D-Methionine transport system 0.626463264424692 25.0 0.626463264424692 0.7633603361968531 8.0 0.7785885707967596 0.1477531142805556 25 -1.0295912009218973 +KEGG-Pathway-pae00360: Phenylalanine metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00360: Phenylalanine metabolism - Pseudomonas aeruginosa PAO1 0.628023899737686 24.0 0.628023899737686 0.7400468791412671 12.0 0.7107897727732283 0.13516901021991248 25 -0.6123139682748789 +KEGG-Pathway-pae00780: Biotin metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00780: Biotin metabolism - Pseudomonas aeruginosa PAO1 0.630550193050193 22.5 0.630550193050193 0.5913688588879251 32.0 0.5888235390455552 0.12456289532298864 25 0.334984618785888 +KEGG-Module-M00208: Glycine betaine/proline transport system KEGG-Module-M00208: Glycine betaine/proline transport system 0.630550193050193 22.5 0.630550193050193 0.639631172525909 23.0 0.6104312160510542 0.16157941022509797 25 0.1245144846803861 +KEGG-Pathway-pae00564: Glycerophospholipid metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00564: Glycerophospholipid metabolism - Pseudomonas aeruginosa PAO1 0.635630269419251 21.0 0.635630269419251 0.7923093572481609 5.0 0.7610349465321476 0.20124338374233935 25 -0.6231493169159671 +KEGG-Pathway-pae00562: Inositol phosphate metabolism - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00562: Inositol phosphate metabolism - Pseudomonas aeruginosa PAO1 0.670165536773742 19.0 0.670165536773742 0.5589734228971961 36.0 0.5545756471642044 0.17195582180314312 25 0.672206898245447 +KEGG-Pathway-pae00280: Valine, leucine and isoleucine degradation - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00280: Valine, leucine and isoleucine degradation - Pseudomonas aeruginosa PAO1 0.670165536773742 19.0 0.670165536773742 0.24624116230824203 71.0 0.349341130956075 0.27815904588778434 25 1.1533847651573226 +KEGG-Module-M00644: Multidrug resistance, efflux pump MexHI-OprD KEGG-Module-M00644: Multidrug resistance, efflux pump MexHI-OprD 0.670165536773742 19.0 0.670165536773742 0.454798207005001 47.0 0.5005277287988699 0.19123403689668786 25 0.8870691155597848 +KEGG-Pathway-pae00072: Synthesis and degradation of ketone bodies - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae00072: Synthesis and degradation of ketone bodies - Pseudomonas aeruginosa PAO1 0.6827460348870671 17.0 0.6827460348870671 0.366639126187358 54.0 0.46016050636761635 0.23473694482267912 25 0.9482338993872158 +KEGG-Module-M00530: Dissimilatory nitrate reduction, nitrate => ammonia KEGG-Module-M00530: Dissimilatory nitrate reduction, nitrate => ammonia 0.6842998955067919 16.0 0.6842998955067919 0.7494990265275692 11.0 0.690616107327317 0.23838236843047378 25 -0.026496136698831753 +KEGG-Module-M00236: Putative polar amino acid transport system KEGG-Module-M00236: Putative polar amino acid transport system 0.696332100384621 15.0 0.696332100384621 0.323832398338802 61.0 0.3532708375528111 0.2233156870384219 25 1.5362165881915208 +KEGG-Pathway-pae01040: Biosynthesis of unsaturated fatty acids - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae01040: Biosynthesis of unsaturated fatty acids - Pseudomonas aeruginosa PAO1 0.7535043453882809 14.0 0.7535043453882809 0.5607523869167299 35.0 0.5586831739373981 0.1444948284409708 25 1.348291655507044 +KEGG-Pathway-pae03070: Bacterial secretion system - Pseudomonas aeruginosa PAO1 KEGG-Pathway-pae03070: Bacterial secretion system - Pseudomonas aeruginosa PAO1 0.7663230567272191 13.0 0.7663230567272191 0.7612670366394431 9.0 0.7161641810929705 0.19695987898845893 25 0.254665447053751 +KEGG-Pathway-pae00643: Styrene degradation - Pseudomonas 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00000000..125c5dd7 --- /dev/null +++ b/pseudomonas_analysis/models/NN_2500_30_pao1/tybalt_2layer_30latent_encoder_weights.h5 @@ -0,0 +1,3 @@ +version https://git-lfs.github.com/spec/v1 +oid sha256:9aedf6257f44afaf2c7e304f5a8331d1225461a93b5371f1bd514a313cce0855 +size 55862776 diff --git a/pseudomonas_analysis/nbconverted/0_prepare_reference_gene_file.py b/pseudomonas_analysis/nbconverted/0_prepare_reference_gene_file.py new file mode 100644 index 00000000..31df733f --- /dev/null +++ b/pseudomonas_analysis/nbconverted/0_prepare_reference_gene_file.py @@ -0,0 +1,130 @@ +#!/usr/bin/env python +# coding: utf-8 + +# # Prepare reference gene file +# +# This notebook creates a reference gene ranking file to use to compare SOPHIE generated gene ranking. The reference ranking information is obtained from [this repository](https://github.com/DartmouthStantonLab/GAPE). This [RDS object](https://github.com/DartmouthStantonLab/GAPE/blob/main/Pa_GPL84_refine_ANOVA_List_unzip.rds) contains 73 experiments. For each experiment, we will identify DEGs using log2FC > 1 and FDR < 0.05. We will rank genes by the proportion that they appeared as DE. + +# In[1]: + + +get_ipython().run_line_magic('load_ext', 'autoreload') +get_ipython().run_line_magic('autoreload', '2') + +import os +import pandas as pd +import rpy2.robjects as ro +from rpy2.robjects import pandas2ri +from rpy2.robjects.conversion import localconverter + +from ponyo import utils + + +# In[2]: + + +# Read in config variables +base_dir = os.path.abspath(os.path.join(os.getcwd(),"../")) + +config_filename = os.path.abspath(os.path.join(base_dir, + "configs", + "config_pseudomonas_33245.tsv")) +params = utils.read_config(config_filename) + + +# In[3]: + + +# Load params +local_dir = params["local_dir"] +reference_gene_filename = os.path.join(local_dir,"Pa_GPL84_refine_ANOVA_List_unzip.rds") + + +# In[4]: + + +readRDS = ro.r['readRDS'] + + +# In[5]: + + +reference_Robject = readRDS(reference_gene_filename) + + +# In[6]: + + +# For each experiment get df +# For each df, if label gene as DEGs based on log2FC>1 and FDR<0.05 +# Concatenate series +num_experiments = len(reference_Robject) +reference_stats_df = pd.DataFrame() + +for i in range(num_experiments): + # Get df for experiment + reference_df = pandas2ri.ri2py(reference_Robject[i]) + + reference_df = reference_df.set_index("ProbeID") + + # Find DEGs + degs_ids = list(reference_df[(abs(reference_df["Log2FC"])>1) & (reference_df["FDR"]<0.05)].index) + reference_df["DEG"] = 0 + reference_df.loc[degs_ids, "DEG"] = 1 + + # Create df with labels for if gene is DE or not + if i == 0: + reference_stats_df = reference_df["DEG"].to_frame("experiment_0") + else: + reference_stats_df = pd.merge( + reference_stats_df, + reference_df["DEG"].to_frame(f"experiment_{i}"), + left_index=True, + right_index=True, + how='left' + ) +reference_stats_df + + +# In[7]: + + +# Map `ProbeID` to `IntergenicSpotID` that contains PA#### IDs +example_reference_df = pandas2ri.ri2py(reference_Robject[0]) +example_reference_df.set_index("ProbeID", inplace=True) + +merged_df = pd.merge(reference_stats_df, example_reference_df, left_index=True, right_index=True) + +# Get relevant columns (`IntergenicSpotID` and `experiment_*`) +experiment_cols = [col for col in merged_df.columns if 'experiment_' in col] +merged_df = merged_df[experiment_cols] + +# Aggregate to get ranking of genes +merged_df["prop DEGs"] = merged_df.sum(axis=1)/num_experiments + + +# In[8]: + + +# Extract PA#### ids from `ProbeID` +# This will be used to compare against SOPHIE ranked genes +pao1_ids = [str_ls[0] for str_ls in merged_df.index.str.split("_")] +merged_df["gene id"] = pao1_ids + + +# In[9]: + + +merged_df.head() + + +# In[10]: + + +# Save file +# Here are the names that we will use for the comparison in notebook 2_identify_generic_genes_pathways.ipynb +# DE_prior_filename = output_filename +# ref_gene_col = "gene id" +# ref_rank_col = "prop DEGs" +merged_df.to_csv('GAPE_proportions.txt', sep="\t") + diff --git a/pseudomonas_analysis/nbconverted/0_subset_training_compendium.py b/pseudomonas_analysis/nbconverted/0_subset_training_compendium.py new file mode 100644 index 00000000..2df6247a --- /dev/null +++ b/pseudomonas_analysis/nbconverted/0_subset_training_compendium.py @@ -0,0 +1,136 @@ +#!/usr/bin/env python +# coding: utf-8 + +# # Subset training compendium +# +# This notebook subsets the normalized compendium to only include those samples that use PAO1 strains. This filtered training compendium will be used to examine the hypothesis that the subset of genes that are found to be generic by SOPHIE are not generic using GAPE-curated experiments because SOPHIE is trained on a compendium containing multiple strains, whereas we suspect that the GAPE experiments are only from a single strain (PAO1). So genes that are generic in other strain contexts will not be detected by GAPE. + +# In[1]: + + +get_ipython().run_line_magic('load_ext', 'autoreload') +get_ipython().run_line_magic('autoreload', '2') + +import os +import sys +import pandas as pd + +from ponyo import utils + + +# ### Set parameters for data processing +# +# Most parameters are read from `config_filename`. + +# In[2]: + + +base_dir = os.path.abspath(os.path.join(os.getcwd(), "../")) + +# Read in config variables +config_filename = os.path.abspath( + os.path.join(base_dir, "configs", "config_pseudomonas_pao1.tsv") +) + +params = utils.read_config(config_filename) + +local_dir = params["local_dir"] +dataset_name = params["dataset_name"] +project_id = params['project_id'] +raw_compendium_filename = "https://raw.githubusercontent.com/greenelab/adage/master/Data_collection_processing/Pa_compendium_02.22.2014.pcl" + +# Load metadata file with annotations per sample +metadata_filename = os.path.join( + base_dir, + dataset_name, + "data", + "metadata", + "sample_annotations.tsv") + +# Load metadata file with annotations per sample +sample_id_filename = os.path.join( + base_dir, + dataset_name, + "data", + "metadata", + f"{project_id}_process_samples.tsv") + +# Output filename +out_compendium_filename = params["raw_compendium_filename"] + + +# ## Read data and metadata + +# In[3]: + + +# Read normalized compendium +raw_compendium = pd.read_csv(raw_compendium_filename, sep="\t", index_col=0, header=0).T + +# Read metadata file +metadata = pd.read_csv(metadata_filename, sep="\t", index_col=0, header=0) + +# Read sample id file +project_sample_ids = pd.read_csv(sample_id_filename, sep="\t", index_col=None, header=0) + + +# In[4]: + + +raw_compendium.head() + + +# In[5]: + + +metadata.head() + + +# In[6]: + + +# Get sample ids that have PAO1 strain +pao1_metadata = metadata.loc[metadata["strain"].str.contains("PAO1")] +experiment_ids = list(pao1_metadata.index) + +assert "E-GEOD-33245" in experiment_ids + + +# In[7]: + + +# Get normalized data associated with PAO1 sample ids +pao1_sample_ids = list(pao1_metadata["ml_data_source"]) +print(len(pao1_sample_ids)) + +pao1_raw_compendium = raw_compendium.loc[pao1_sample_ids] + +assert len(pao1_sample_ids) == pao1_raw_compendium.shape[0] + + +# In[8]: + + +# Drop samples with no expression activity associated +pao1_raw_compendium.dropna(inplace=True) + +print(pao1_raw_compendium.shape) +pao1_raw_compendium + + +# In[9]: + + +# Check samples associated with project_id are still in subset +project_sample_ids = list(project_sample_ids["Sample"]) + +for sample_id in project_sample_ids: + assert sample_id in list(pao1_raw_compendium.index) + + +# In[10]: + + +# Save filtered compendium +pao1_raw_compendium.T.to_csv(out_compendium_filename, sep="\t") + diff --git a/pseudomonas_analysis/nbconverted/1_process_pseudomonas_data.py b/pseudomonas_analysis/nbconverted/1_process_pseudomonas_data.py index f2466bce..9d0c3b6e 100644 --- a/pseudomonas_analysis/nbconverted/1_process_pseudomonas_data.py +++ b/pseudomonas_analysis/nbconverted/1_process_pseudomonas_data.py @@ -1,4 +1,4 @@ - +#!/usr/bin/env python # coding: utf-8 # # Process pseudomonas data @@ -25,7 +25,7 @@ from generic_expression_patterns_modules import process -# In[ ]: +# In[2]: # Set seeds to get reproducible VAE trained models @@ -36,14 +36,14 @@ # # Most parameters are read from `config_filename`. We manually selected bioproject [GEOD-33245](https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-33245/?s_sortby=col_8&s_sortorder=ascending), as the template experiment, which contains multiple different comparisons including WT vs *crc* mutants, WT vs *cbr* mutants in different conditions. -# In[2]: +# In[3]: base_dir = os.path.abspath(os.path.join(os.getcwd(), "../")) # Read in config variables config_filename = os.path.abspath( - os.path.join(base_dir, "configs", "config_pseudomonas_33245.tsv") + os.path.join(base_dir, "configs", "config_pseudomonas_pao1.tsv") ) params = utils.read_config(config_filename) @@ -85,7 +85,7 @@ # ### Transpose raw pseudomonas compendium and normalize it # The compendium is from https://raw.githubusercontent.com/greenelab/adage/master/Data_collection_processing/Pa_compendium_02.22.2014.pcl -# In[3]: +# In[4]: process.process_raw_compendium_pseudomonas( @@ -96,6 +96,20 @@ ) +# ## Get raw pseudomonas template experiment + +# In[7]: + + +process.process_raw_template_pseudomonas( + processed_compendium_filename, + project_id, + dataset_name, + metadata_colname, + raw_template_filename, +) + + # **Note:** # * We are training our VAE model using ALL the data in the compendium. # * The template experiment is using a subset of the samples in the real experiment and using those in the DE analysis in order to ensure the comparison of samples with consistent backgrounds (i.e. some experiments have samples with 3 different biological conditions and for now our statistical test is doing a binary comparison). @@ -106,7 +120,7 @@ # ### Train VAE -# In[6]: +# In[5]: # Create VAE directories if needed @@ -123,7 +137,7 @@ os.makedirs(sub_dir, exist_ok=True) -# In[7]: +# In[6]: # Train VAE on new compendium data diff --git a/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways.py b/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways.py index 148ae818..3f3dfed1 100644 --- a/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways.py +++ b/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways.py @@ -1,4 +1,4 @@ - +#!/usr/bin/env python # coding: utf-8 # # Identify generic genes and pathways @@ -106,12 +106,12 @@ gene_summary_filename = os.path.join( base_dir, dataset_name, - f"generic_gene_summary_{project_id}_test.tsv" + f"generic_gene_summary_{project_id}.tsv" ) pathway_summary_filename = os.path.join( base_dir, dataset_name, - f"generic_pathway_summary_{project_id}_test.tsv" + f"generic_pathway_summary_{project_id}.tsv" ) @@ -275,6 +275,54 @@ summary_gene_ranks.to_csv(gene_summary_filename, sep='\t') +# ## Compare gene ranking + +# In[16]: + + +# Get generic genes identified by Crow et. al. +GAPE_filename = params['reference_gene_filename'] +ref_gene_col = params['reference_gene_name_col'] +ref_rank_col = params['reference_rank_col'] + +figure_filename = f"gene_ranking_{col_to_rank_genes}.svg" + +corr, shared_ranking = ranking.compare_gene_ranking( + summary_gene_ranks, + GAPE_filename, + ref_gene_col, + ref_rank_col, + figure_filename +) + + +# In[17]: + + +# Get genes that are highly generic in both +generic_both = shared_ranking[(shared_ranking["Rank (simulated)"]>4500) & (shared_ranking["prop DEGs"]>3500)] +generic_both.to_csv(os.path.join(local_dir, "SOPHIE_GAPE_generic.tsv"), sep="\t") + + +# In[18]: + + +# Get genes that are highly generic by SOPHIE but not by GAPE +generic_SOPHIE_only = shared_ranking[(shared_ranking["Rank (simulated)"]>4500) & (shared_ranking["prop DEGs"]<2000)] +generic_SOPHIE_only.to_csv(os.path.join(local_dir, "SOPHIE_generic_only.tsv"), sep="\t") + + +# **Takeaway:** +# +# * X-axis: gene ranking using SOPHIE (trained on Pseudomonas compendium containing ~1K experiments) +# * Y-axis: gene ranking using GAPE (curated set of 73 experiments) +# +# * Overall there is good consistency between SOPHIE and the reference set of experiments. There is especially more consistency amongst lowly ranked genes (genes that consistently didn’t change or genes that changed in a subset of cases). Perhaps the signal from these low ranked genes are very robust in P. aeruginosa +# * Housekeeping genes make sense as contributing to a very strong consistent signal. +# * What about those inconsistently DE genes? Assuming the 73 contexts are represented in the compendium, then those genes that are in consisten +# * There is some noise in the bottom right corner (i.e. genes that the reference didn't think were as generic but SOPHIE did). These might be the result of the reference being limited to 73 experiments and differences in data processing (ANOVA vs RMA). +# * Assuming the 73 contexts are represented in the compendium, if a gene is generic in the compendium, then this gene was found to be DE across many contexts, including the subset of 73 contexts. We suspect the reason for generic genes being highly generic in the compendium but NOT in the 73 experiments is because the signal to noise ratio will be lower in the smaller subset that reduce the generic signal. + # ### GSEA # **Goal:** To detect modest but coordinated changes in prespecified sets of related genes (i.e. those genes in the same pathway or share the same GO term). # @@ -282,21 +330,21 @@ # 2. An enrichment score (ES) is defined as the maximum distance from the middle of the ranked list. Thus, the enrichment score indicates whether the genes contained in a gene set are clustered towards the beginning or the end of the ranked list (indicating a correlation with change in expression). # 3. Estimate the statistical significance of the ES by a phenotypic-based permutation test in order to produce a null distribution for the ES( i.e. scores based on permuted phenotype) -# In[16]: +# In[19]: # Create "/GSEA_stats/" subdirectory -os.makedirs(os.path.join(local_dir, "GSEA_stats"), exist_ok=True) +os.makedirs(os.path.join(local_dir, "GSA_stats"), exist_ok=True) -# In[17]: +# In[20]: # Load pathway data adage_kegg_DB_filename = params['pathway_DB_filename'] -# In[18]: +# In[21]: # Need to format data into tab-delimited matrix @@ -312,34 +360,34 @@ stats.format_pseudomonas_pathway_DB(adage_kegg_DB_filename, local_dir, adage_kegg_DB_processed_filename) -# In[19]: +# In[22]: -get_ipython().run_cell_magic('R', '-i base_dir -i template_DE_stats_filename -i adage_kegg_DB_processed_filename -i statistic -o template_enriched_pathways', "\nsource(paste0(base_dir, '/generic_expression_patterns_modules/GSEA_analysis.R'))\ntemplate_enriched_pathways <- find_enriched_pathways(template_DE_stats_filename, adage_kegg_DB_processed_filename, statistic)") +get_ipython().run_cell_magic('R', '-i base_dir -i template_DE_stats_filename -i adage_kegg_DB_processed_filename -i statistic -o template_enriched_pathways', '\nsource(paste0(base_dir, \'/generic_expression_patterns_modules/GSEA_analysis.R\'))\n\nout_filename <- paste(local_dir, \n "GSA_stats/GSEA_stats_template_data_",\n project_id,\n "_real.txt", \n sep = "")\n\ntemplate_enriched_pathways <- find_enriched_pathways(template_DE_stats_filename, adage_kegg_DB_processed_filename, statistic)\nwrite.table(as.data.frame(template_enriched_pathways[1:7]), file = out_filename, row.names = F, sep = "\\t")') -# In[20]: +# In[23]: print(template_enriched_pathways.shape) template_enriched_pathways[template_enriched_pathways['padj'] < 0.05].sort_values(by='padj').head() -# In[21]: +# In[24]: -get_ipython().run_cell_magic('R', '-i project_id -i local_dir -i adage_kegg_DB_processed_filename -i num_runs -i statistic', '\nsource(paste0(base_dir, \'/generic_expression_patterns_modules/GSEA_analysis.R\'))\n\n# New files created: "/GSEA_stats/GSEA_stats_simulated_data__.txt"\nfor (i in 0:(num_runs-1)) {\n simulated_DE_stats_filename <- paste(local_dir, \n "DE_stats/DE_stats_simulated_data_", \n project_id,\n "_", \n i,\n ".txt",\n sep = "")\n \n out_filename <- paste(local_dir, \n "GSEA_stats/GSEA_stats_simulated_data_",\n project_id,\n "_",\n i,\n ".txt", \n sep = "")\n \n enriched_pathways <- find_enriched_pathways(simulated_DE_stats_filename, adage_kegg_DB_processed_filename, statistic) \n \n # Remove column with leading edge since its causing parsing issues\n write.table(as.data.frame(enriched_pathways[1:7]), file = out_filename, row.names = F, sep = "\\t")\n}') +get_ipython().run_cell_magic('R', '-i project_id -i local_dir -i adage_kegg_DB_processed_filename -i num_runs -i statistic', '\nsource(paste0(base_dir, \'/generic_expression_patterns_modules/GSEA_analysis.R\'))\n\n# New files created: "/GSEA_stats/GSEA_stats_simulated_data__.txt"\nfor (i in 0:(num_runs-1)) {\n simulated_DE_stats_filename <- paste(local_dir, \n "DE_stats/DE_stats_simulated_data_", \n project_id,\n "_", \n i,\n ".txt",\n sep = "")\n \n out_filename <- paste(local_dir, \n "GSA_stats/GSEA_stats_simulated_data_",\n project_id,\n "_",\n i,\n ".txt", \n sep = "")\n \n enriched_pathways <- find_enriched_pathways(simulated_DE_stats_filename, adage_kegg_DB_processed_filename, statistic) \n \n # Remove column with leading edge since its causing parsing issues\n write.table(as.data.frame(enriched_pathways[1:7]), file = out_filename, row.names = F, sep = "\\t")\n}') # ### Rank pathways -# In[22]: +# In[25]: -analysis_type = "GSEA" +analysis_type = "GSA" template_GSEA_stats_filename = os.path.join( local_dir, - "GSEA_stats", + "GSA_stats", f"GSEA_stats_template_data_{project_id}_real.txt" ) template_GSEA_stats, simulated_GSEA_summary_stats = ranking.process_and_rank_genes_pathways( @@ -349,12 +397,13 @@ project_id, analysis_type, col_to_rank_pathways, + "GSEA" ) # ### Pathway summary table -# In[23]: +# In[26]: # Create intermediate file: "/gene_summary_table_.tsv" @@ -371,7 +420,7 @@ summary_pathway_ranks.sort_values(by='Rank (simulated)', ascending=False).head() -# In[24]: +# In[27]: # Create `pathway_summary_filename` diff --git a/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways_pao1.py b/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways_pao1.py new file mode 100644 index 00000000..a102c5c0 --- /dev/null +++ b/pseudomonas_analysis/nbconverted/2_identify_generic_genes_pathways_pao1.py @@ -0,0 +1,655 @@ +#!/usr/bin/env python +# coding: utf-8 + +# # Identify generic genes and pathways using subset of training compendium +# +# Studies have found that some genes are more likely to be differentially expressed even across a wide range of experimental designs. These generic genes and subsequent pathways are not necessarily specific to the biological process being studied but instead represent a more systematic change. +# +# We have developed an approach, outlined below, to automatically identify these generic genes and pathways. We have validated this simulation approach can identify generic genes and pathways in the analysis notebooks: [human_general_analysis](../human_general_analysis/) and [human_cancer_analysis](../human_cancer_analysis/). Here +# +# This notebook applies this approach to identify generic genes and pathways in the pseudomonas compendium. +# +# **Steps to identify generic genes:** +# 1. Simulates N gene expression experiments using [ponyo](https://github.com/ajlee21/ponyo) +# 2. Perform DE analysis to get association statistics for each gene +# +# In this case the DE analysis is based on the experimental design of the template experiment, described in the previous [notebook](1_process_pseudomonas_data.ipynb). +# The template experiment is [GEOD-33245](https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-33245/?s_sortby=col_8&s_sortorder=ascending), which contains multiple different comparisons including WT vs *crc* mutants, WT vs *cbr* mutants in different conditions. So the DE analysis is comparing WT vs mutant. +# +# 3. For each gene, aggregate statistics across all simulated experiments +# 4. Rank genes based on this aggregated statistic +# +# **Steps to identify generic gene sets (pathways):** +# 1. Using the same simulated experiments from above, perform GSEA analysis. This analysis will determine whether the genes contained in a gene set are clustered towards the beginning or the end of the ranked list of genes, where genes are ranked by log fold change, indicating a correlation with change in expression. +# 2. For each gene set (pathway), aggregate statistics across all simulated experiments +# 3. Rank gene sets based on this aggregated statistic + +# In[1]: + + +get_ipython().run_line_magic('load_ext', 'autoreload') +get_ipython().run_line_magic('load_ext', 'rpy2.ipython') +get_ipython().run_line_magic('autoreload', '2') + +import os +import sys +import glob +import pandas as pd +import numpy as np +import seaborn as sns +import pickle + +from rpy2.robjects import pandas2ri +pandas2ri.activate() + +from ponyo import utils, simulate_expression_data +from generic_expression_patterns_modules import process, stats, ranking + +np.random.seed(123) + + +# In[2]: + + +# Read in config variables +base_dir = os.path.abspath(os.path.join(os.getcwd(),"../")) + +config_filename = os.path.abspath(os.path.join(base_dir, + "configs", + "config_pseudomonas_pao1.tsv")) +params = utils.read_config(config_filename) + + +# In[3]: + + +# Load params +local_dir = params["local_dir"] +dataset_name = params['dataset_name'] +NN_architecture = params['NN_architecture'] +num_runs = params['num_simulated'] +project_id = params['project_id'] +metadata_col_id = params['metadata_colname'] +raw_template_filename = params['raw_template_filename'] +processed_template_filename = params['processed_template_filename'] +normalized_compendium_filename = params['normalized_compendium_filename'] +scaler_filename = params['scaler_filename'] +col_to_rank_genes = params['rank_genes_by'] +col_to_rank_pathways = params['rank_pathways_by'] +statistic = params['gsea_statistic'] + +# Load metadata file with grouping assignments for samples +sample_id_metadata_filename = os.path.join( + base_dir, + dataset_name, + "data", + "metadata", + f"{project_id}_process_samples.tsv") + +# Load metadata file with grouping assignments for samples +metadata_filename = os.path.join( + base_dir, + dataset_name, + "data", + "metadata", + f"{project_id}_groups.tsv" +) + +# Load pickled file +scaler = pickle.load(open(scaler_filename, "rb")) + + +# In[4]: + + +# Output files +gene_summary_filename = os.path.join( + base_dir, + dataset_name, + f"generic_gene_summary_{project_id}_pao1.tsv" +) +pathway_summary_filename = os.path.join( + base_dir, + dataset_name, + f"generic_pathway_summary_{project_id}_pao1.tsv" +) + + +# ### Simulate experiments using selected template experiment +# Workflow: +# +# 1. Get the gene expression data for the selected template experiment +# 2. Encode this experiment into a latent space using the trained VAE model +# 3. Linearly shift the encoded template experiment in the latent space +# 4. Decode the samples. This results in a new experiment +# 5. Repeat steps 1-4 to get multiple simulated experiments + +# In[5]: + + +# Note: We are manually changing the function to suit our nex experiment where we +# subset our training compendium. Ponyo will be updated to address this change to +# be more robust to user inputs +import glob +import warnings +from keras.models import load_model +from sklearn import preprocessing + +def get_sample_ids(experiment_id, dataset_name, sample_id_colname): + """ + Returns sample ids (found in gene expression df) associated with + a given list of experiment ids (found in the metadata) + + Arguments + ---------- + experiment_ids_file: str + File containing all cleaned experiment ids + + dataset_name: str + Name for analysis directory. Either "Human" or "Pseudomonas" + + sample_id_colname: str + Column header that contains sample id that maps expression data + and metadata + + """ + base_dir = os.path.abspath(os.path.join(os.getcwd(), "../")) + + if "pseudomonas" in dataset_name.lower(): + # metadata file + mapping_file = os.path.join( + base_dir, dataset_name, "data", "metadata", "sample_annotations.tsv" + ) + + # Read in metadata + metadata = pd.read_csv(mapping_file, header=0, sep="\t", index_col=0) + + selected_metadata = metadata.loc[experiment_id] + sample_ids = list(selected_metadata[sample_id_colname]) + + else: + # metadata file + mapping_file = os.path.join( + base_dir, dataset_name, "data", "metadata", "recount2_metadata.tsv" + ) + + # Read in metadata + metadata = pd.read_csv(mapping_file, header=0, sep="\t", index_col=0) + + selected_metadata = metadata.loc[experiment_id] + sample_ids = list(selected_metadata[sample_id_colname]) + + return sample_ids + +def shift_template_experiment_tmp( + normalized_data_file, + selected_experiment_id, + sample_id_colname, + NN_architecture, + dataset_name, + scaler, + local_dir, + base_dir, + run, +): + """ + Generate new simulated experiment using the selected_experiment_id as a template + experiment and shifting this template experiment in the latent space to a new + location. This shifted experiment will be the new simulated experiment. + + This will return a file with a single simulated experiment following the workflow mentioned. + This function can be run multiple times to generate multiple simulated experiments from a + single selected_experiment_id. + + Arguments + ---------- + normalized_data_file: str + File containing normalized gene expression data + + ------------------------------| PA0001 | PA0002 |... + 05_PA14000-4-2_5-10-07_S2.CEL | 0.8533 | 0.7252 |... + 54375-4-05.CEL | 0.7789 | 0.7678 |... + ... | ... | ... |... + + selected_experiment_id: str + Experiment id selected as template + + sample_id_colname: str + Column header that contains sample id that maps expression data and metadata + + NN_architecture: str + Name of neural network architecture to use. + Format 'NN__' + + dataset_name: str + Name for analysis directory. Either "Human" or "Pseudomonas" + + scaler: minmax model + Model used to transform data into a different range + + local_dir: str + Parent directory on local machine to store intermediate results + + base_dir: str + Root directory containing analysis subdirectories + + run: int + Simulation run + + Returns + -------- + simulated_data_file: str + File containing simulated gene expression data + + """ + + # Files + NN_dir = os.path.join(base_dir, dataset_name, "models", NN_architecture) + latent_dim = NN_architecture.split("_")[-2] # Here we manually changed the index to work + + model_encoder_file = glob.glob(os.path.join(NN_dir, "*_encoder_model.h5"))[0] + + weights_encoder_file = glob.glob(os.path.join(NN_dir, "*_encoder_weights.h5"))[0] + + model_decoder_file = glob.glob(os.path.join(NN_dir, "*_decoder_model.h5"))[0] + + weights_decoder_file = glob.glob(os.path.join(NN_dir, "*_decoder_weights.h5"))[0] + + # Load saved models + loaded_model = load_model(model_encoder_file, compile=False) + loaded_decode_model = load_model(model_decoder_file, compile=False) + + loaded_model.load_weights(weights_encoder_file) + loaded_decode_model.load_weights(weights_decoder_file) + + # Read data + normalized_data = pd.read_csv(normalized_data_file, header=0, sep="\t", index_col=0) + + # Get corresponding sample ids + sample_ids = get_sample_ids(selected_experiment_id, dataset_name, sample_id_colname) + + # Gene expression data for selected samples + selected_data_df = normalized_data.loc[sample_ids] + + # Encode selected experiment into latent space + data_encoded = loaded_model.predict_on_batch(selected_data_df) + data_encoded_df = pd.DataFrame(data_encoded, index=selected_data_df.index) + + # Get centroid of original data + centroid = data_encoded_df.mean(axis=0) + + # Add individual vectors(centroid, sample point) to new_centroid + + # Encode original gene expression data into latent space + data_encoded_all = loaded_model.predict_on_batch(normalized_data) + data_encoded_all_df = pd.DataFrame(data_encoded_all, index=normalized_data.index) + + data_encoded_all_df.head() + + # Find a new location in the latent space by sampling from the latent space + encoded_means = data_encoded_all_df.mean(axis=0) + encoded_stds = data_encoded_all_df.std(axis=0) + + latent_dim = int(latent_dim) + new_centroid = np.zeros(latent_dim) + + for j in range(latent_dim): + new_centroid[j] = np.random.normal(encoded_means[j], encoded_stds[j]) + + shift_vec_df = new_centroid - centroid + + simulated_data_encoded_df = data_encoded_df.apply( + lambda x: x + shift_vec_df, axis=1 + ) + + # Decode simulated data into raw gene space + simulated_data_decoded = loaded_decode_model.predict_on_batch( + simulated_data_encoded_df + ) + + simulated_data_decoded_df = pd.DataFrame( + simulated_data_decoded, + index=simulated_data_encoded_df.index, + columns=selected_data_df.columns, + ) + + # Un-normalize the data in order to run DE analysis downstream + simulated_data_scaled = scaler.inverse_transform(simulated_data_decoded_df) + + simulated_data_scaled_df = pd.DataFrame( + simulated_data_scaled, + columns=simulated_data_decoded_df.columns, + index=simulated_data_decoded_df.index, + ) + + # Save template data for visualization validation + test_file = os.path.join( + local_dir, + "pseudo_experiment", + "template_normalized_data_" + selected_experiment_id + "_test.txt", + ) + + selected_data_df.to_csv(test_file, float_format="%.3f", sep="\t") + + # Save + out_file = os.path.join( + local_dir, + "pseudo_experiment", + "selected_simulated_data_" + selected_experiment_id + "_" + str(run) + ".txt", + ) + + simulated_data_scaled_df.to_csv(out_file, float_format="%.3f", sep="\t") + + out_encoded_file = os.path.join( + local_dir, + "pseudo_experiment", + f"selected_simulated_encoded_data_{selected_experiment_id}_{run}.txt", + ) + + simulated_data_encoded_df.to_csv(out_encoded_file, float_format="%.3f", sep="\t") + + +# In[6]: + + +# Simulate multiple experiments +# This step creates the following files in "/pseudo_experiment/" directory: +# - selected_simulated_data_SRP012656_.txt +# - selected_simulated_encoded_data_SRP012656_.txt +# - template_normalized_data_SRP012656_test.txt +# in which "" is an integer in the range of [0, num_runs-1] +os.makedirs(os.path.join(local_dir, "pseudo_experiment"), exist_ok=True) +for run_id in range(num_runs): + shift_template_experiment_tmp( + normalized_compendium_filename, + project_id, + metadata_col_id, + NN_architecture, + dataset_name, + scaler, + local_dir, + base_dir, + run_id) + + +# ### Process template and simulated data +# +# * Remove samples not required for comparison. +# * Make sure ordering of samples matches metadata for proper comparison + +# In[7]: + + +if not os.path.exists(sample_id_metadata_filename): + sample_id_metadata_filename = None + +stats.process_samples_for_limma( + raw_template_filename, + metadata_filename, + processed_template_filename, + sample_id_metadata_filename, +) + +for i in range(num_runs): + simulated_filename = os.path.join( + local_dir, + "pseudo_experiment", + f"selected_simulated_data_{project_id}_{i}.txt" + ) + stats.process_samples_for_limma( + simulated_filename, + metadata_filename, + None, + sample_id_metadata_filename, +) + + +# In[8]: + + +# Quick check +template_data = pd.read_csv( + processed_template_filename, + header=0, + index_col=0, + sep="\t" +) + +assert(template_data.shape[0] == 4) + + +# ### Differential expression analysis + +# In[9]: + + +# Create subdirectory: "/DE_stats/" +os.makedirs(os.path.join(local_dir, "DE_stats"), exist_ok=True) + + +# In[10]: + + +get_ipython().run_cell_magic('R', '-i metadata_filename -i project_id -i processed_template_filename -i local_dir -i base_dir', '\nsource(paste0(base_dir, \'/generic_expression_patterns_modules/DE_analysis.R\'))\n\nget_DE_stats_limma(metadata_filename,\n project_id, \n processed_template_filename,\n "template",\n local_dir,\n "real")') + + +# In[11]: + + +get_ipython().run_cell_magic('R', '-i metadata_filename -i project_id -i base_dir -i local_dir -i num_runs -o num_sign_DEGs_simulated', '\nsource(paste0(base_dir,\'/generic_expression_patterns_modules/DE_analysis.R\'))\n\nnum_sign_DEGs_simulated <- c()\n\nfor (i in 0:(num_runs-1)){\n simulated_data_filename <- paste(\n local_dir, \n "pseudo_experiment/selected_simulated_data_",\n project_id,\n "_", \n i,\n ".txt",\n sep=""\n )\n \n run_output <- get_DE_stats_limma(\n metadata_filename,\n project_id, \n simulated_data_filename,\n "simulated",\n local_dir,\n i\n )\n num_sign_DEGs_simulated <- c(num_sign_DEGs_simulated, run_output)\n}') + + +# ### Rank genes + +# In[12]: + + +analysis_type = "DE" +template_DE_stats_filename = os.path.join( + local_dir, + "DE_stats", + f"DE_stats_template_data_{project_id}_real.txt" +) +template_DE_stats, simulated_DE_summary_stats = ranking.process_and_rank_genes_pathways( + template_DE_stats_filename, + local_dir, + num_runs, + project_id, + analysis_type, + col_to_rank_genes, +) + + +# ### Gene summary table + +# In[13]: + + +summary_gene_ranks = ranking.generate_summary_table( + template_DE_stats_filename, + template_DE_stats, + simulated_DE_summary_stats, + col_to_rank_genes, + local_dir, + 'gene', + params +) + +summary_gene_ranks.sort_values(by="Z score", ascending=False).head() + + +# In[14]: + + +# Add gene name as column to summary dataframe +summary_gene_ranks = ranking.add_pseudomonas_gene_name_col(summary_gene_ranks, base_dir) +summary_gene_ranks.sort_values(by="Z score", ascending=False).head() + + +# In[15]: + + +# Check if there is an NaN values, there should not be +summary_gene_ranks.isna().any() + + +# In[16]: + + +# Create `gene_summary_filename` +summary_gene_ranks.to_csv(gene_summary_filename, sep='\t') + + +# ## Compare gene ranking + +# In[17]: + + +# Get generic genes identified by Crow et. al. +GAPE_filename = params['reference_gene_filename'] +ref_gene_col = params['reference_gene_name_col'] +ref_rank_col = params['reference_rank_col'] + +figure_filename = f"gene_ranking_{col_to_rank_genes}_pao1.svg" + +corr, shared_ranking = ranking.compare_gene_ranking( + summary_gene_ranks, + GAPE_filename, + ref_gene_col, + ref_rank_col, + figure_filename +) + + +# In[18]: + + +# Get genes that are highly generic in both +generic_both = shared_ranking[(shared_ranking["Rank (simulated)"]>4500) & (shared_ranking["prop DEGs"]>3500)] +generic_both.to_csv(os.path.join(local_dir, "SOPHIE_GAPE_generic.tsv"), sep="\t") + + +# In[19]: + + +# Get genes that are highly generic by SOPHIE but not by GAPE +generic_SOPHIE_only = shared_ranking[(shared_ranking["Rank (simulated)"]>4500) & (shared_ranking["prop DEGs"]<2000)] +generic_SOPHIE_only.to_csv(os.path.join(local_dir, "SOPHIE_generic_only.tsv"), sep="\t") + + +# **Takeaway:** +# +# * X-axis: gene ranking using SOPHIE (trained on Pseudomonas compendium containing ~1K experiments) +# * Y-axis: gene ranking using GAPE (curated set of 73 experiments) +# +# * Compared to the correlation plot comparing SOPHIE trained on the full pseudomonas compendium vs GAPE experiments [here](2_identify_generic_genes_pathways.ipynb), it looks like there is more noise in the above correlation plot. Looking up the experiment ids associated with GAPE [here](https://github.com/DartmouthStantonLab/GAPE/blob/main/Pa_GSEnum_unzip.rds) it looks like GAPE does contain a mix of PAO1, PA14 and clinical strains. So by subsetting out training compendium to only represent PAO1 patterns, which is adding more noise to the bottom left of the plot as expected (genes that GAPE finds generic are not found by SOPHIE due to our limited representation in our training compendium) + +# ### GSEA +# **Goal:** To detect modest but coordinated changes in prespecified sets of related genes (i.e. those genes in the same pathway or share the same GO term). +# +# 1. Ranks all genes based using DE association statistics. +# 2. An enrichment score (ES) is defined as the maximum distance from the middle of the ranked list. Thus, the enrichment score indicates whether the genes contained in a gene set are clustered towards the beginning or the end of the ranked list (indicating a correlation with change in expression). +# 3. Estimate the statistical significance of the ES by a phenotypic-based permutation test in order to produce a null distribution for the ES( i.e. scores based on permuted phenotype) + +# In[20]: + + +# Create "/GSEA_stats/" subdirectory +os.makedirs(os.path.join(local_dir, "GSA_stats"), exist_ok=True) + + +# In[21]: + + +# Load pathway data +adage_kegg_DB_filename = params['pathway_DB_filename'] + + +# In[22]: + + +# Need to format data into tab-delimited matrix +# with columns= KEGG pathway name, description, gene ids +# Each gene ids is tab separated +adage_kegg_DB_processed_filename = os.path.join( + base_dir, + dataset_name, + "data", + "metadata", + "adage_kegg_DB_process_filename.gmt" +) +stats.format_pseudomonas_pathway_DB(adage_kegg_DB_filename, local_dir, adage_kegg_DB_processed_filename) + + +# In[23]: + + +get_ipython().run_cell_magic('R', '-i base_dir -i template_DE_stats_filename -i adage_kegg_DB_processed_filename -i statistic -o template_enriched_pathways', '\nsource(paste0(base_dir, \'/generic_expression_patterns_modules/GSEA_analysis.R\'))\n\nout_filename <- paste(local_dir, \n "GSA_stats/GSEA_stats_template_data_",\n project_id,\n "_real.txt", \n sep = "")\n\ntemplate_enriched_pathways <- find_enriched_pathways(template_DE_stats_filename, adage_kegg_DB_processed_filename, statistic)\nwrite.table(as.data.frame(template_enriched_pathways[1:7]), file = out_filename, row.names = F, sep = "\\t")') + + +# In[24]: + + +print(template_enriched_pathways.shape) +template_enriched_pathways[template_enriched_pathways['padj'] < 0.05].sort_values(by='padj').head() + + +# In[25]: + + +get_ipython().run_cell_magic('R', '-i project_id -i local_dir -i adage_kegg_DB_processed_filename -i num_runs -i statistic', '\nsource(paste0(base_dir, \'/generic_expression_patterns_modules/GSEA_analysis.R\'))\n\n# New files created: "/GSEA_stats/GSEA_stats_simulated_data__.txt"\nfor (i in 0:(num_runs-1)) {\n simulated_DE_stats_filename <- paste(local_dir, \n "DE_stats/DE_stats_simulated_data_", \n project_id,\n "_", \n i,\n ".txt",\n sep = "")\n \n out_filename <- paste(local_dir, \n "GSA_stats/GSEA_stats_simulated_data_",\n project_id,\n "_",\n i,\n ".txt", \n sep = "")\n \n enriched_pathways <- find_enriched_pathways(simulated_DE_stats_filename, adage_kegg_DB_processed_filename, statistic) \n \n # Remove column with leading edge since its causing parsing issues\n write.table(as.data.frame(enriched_pathways[1:7]), file = out_filename, row.names = F, sep = "\\t")\n}') + + +# ### Rank pathways + +# In[26]: + + +analysis_type = "GSA" +template_GSEA_stats_filename = os.path.join( + local_dir, + "GSA_stats", + f"GSEA_stats_template_data_{project_id}_real.txt" +) +template_GSEA_stats, simulated_GSEA_summary_stats = ranking.process_and_rank_genes_pathways( + template_GSEA_stats_filename, + local_dir, + num_runs, + project_id, + analysis_type, + col_to_rank_pathways, + "GSEA" +) + + +# ### Pathway summary table + +# In[27]: + + +# Create intermediate file: "/gene_summary_table_.tsv" +summary_pathway_ranks = ranking.generate_summary_table( + template_GSEA_stats_filename, + template_GSEA_stats, + simulated_GSEA_summary_stats, + col_to_rank_pathways, + local_dir, + 'pathway', + params +) + +summary_pathway_ranks.sort_values(by='Rank (simulated)', ascending=False).head() + + +# In[29]: + + +# Create `pathway_summary_filename` +summary_pathway_ranks.to_csv(pathway_summary_filename, sep='\t') + + +# **Quick check:** +# +# Looks like Ribosomes are found to be significantly differentiated in the template and across 25 simulated experiments. So this pathway looks to be generic, which is consistent with findings from [Crow. et. al.](https://www.pnas.org/content/116/13/6491.abstract), using Human data. This is also consistent with [paper](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679180/) which observed that Ribosome proteins have many different functions in *S. cerevisiae*, which might explain their variability across a wide range of contexts. +# +# * Need to think about why it might make sense that Ribosomes being generic in Humans would also imply that they are generic in P. aeruginosa. diff --git a/pseudomonas_analysis/nbconverted/viz_expression_data.py b/pseudomonas_analysis/nbconverted/viz_expression_data.py index ae474a20..e451d766 100644 --- a/pseudomonas_analysis/nbconverted/viz_expression_data.py +++ b/pseudomonas_analysis/nbconverted/viz_expression_data.py @@ -1,4 +1,4 @@ - +#!/usr/bin/env python # coding: utf-8 # # Visualize gene expression diff --git a/tests/2_identify_generic_genes_pathways.ipynb b/tests/2_identify_generic_genes_pathways.ipynb index 033bfdeb..6f6994b1 100644 --- a/tests/2_identify_generic_genes_pathways.ipynb +++ b/tests/2_identify_generic_genes_pathways.ipynb @@ -2416,7 +2416,7 @@ "\n", "figure_filename = f\"gene_ranking_{col_to_rank_genes}.svg\"\n", "\n", - "corr_stats = ranking.compare_gene_ranking(\n", + "corr_stats, shared_ranking = ranking.compare_gene_ranking(\n", " summary_gene_ranks,\n", " DE_prior_file,\n", " ref_gene_col,\n", diff --git a/tests/nbconverted/2_identify_generic_genes_pathways.py b/tests/nbconverted/2_identify_generic_genes_pathways.py index 383c107c..bdb9dba9 100644 --- a/tests/nbconverted/2_identify_generic_genes_pathways.py +++ b/tests/nbconverted/2_identify_generic_genes_pathways.py @@ -366,7 +366,7 @@ figure_filename = f"gene_ranking_{col_to_rank_genes}.svg" -corr_stats = ranking.compare_gene_ranking( +corr_stats, shared_ranking = ranking.compare_gene_ranking( summary_gene_ranks, DE_prior_file, ref_gene_col,