decima version=0.2.2, gene_expression prediction, sequence shifting and fine-tuning

src/decima/cli/__init__.py

@@ -6,8 +6,8 @@
 from decima.cli.attributions import cli_attributions
 from decima.cli.query_cell import cli_query_cell
 from decima.cli.vep import cli_predict_variant_effect
+from decima.cli.finetune import cli_finetune
 from decima.cli.vep import cli_vep_ensemble
-# from decima.cli.finetune import cli_finetune
 
 
 logger = logging.getLogger("decima")
@@ -33,6 +33,7 @@ def main():
 main.add_command(cli_attributions, name="attributions")
 main.add_command(cli_query_cell, name="query-cell")
 main.add_command(cli_predict_variant_effect, name="vep")
+main.add_command(cli_finetune, name="finetune")
 main.add_command(cli_vep_ensemble, name="vep-ensemble")
 
 

src/decima/cli/finetune.py

@@ -1,6 +1,5 @@
 """Finetune the Decima model."""
-
-import os
+import logging
 import click
 import anndata
 import wandb
@@ -9,62 +8,74 @@
 
 
 @click.command()
-@click.option("--name", required=True, help="Project name")
-@click.option("--dir", required=True, help="Data directory path")
-@click.option("--lr", default=0.001, type=float, help="Learning rate")
-@click.option("--weight", required=True, type=float, help="Weight parameter")
-@click.option("--grad", required=True, type=int, help="Gradient accumulation steps")
-@click.option("--replicate", default=0, type=int, help="Replication number")
-@click.option("--bs", default=4, type=int, help="Batch size")
-def cli_finetune(name, dir, lr, weight, grad, replicate, bs):
+@click.option("--name", required=True, help="Name of the run.")
+@click.option("--model", default="0", type=str, help="Model path or replication number. If a path is provided, the model will be loaded from the path. If a replication number is provided, the model will be loaded from the replication number.")
+@click.option("--matrix-file", required=True, help="Matrix file path.")
+@click.option("--h5-file", required=True, help="H5 file path.")
+@click.option("--outdir", required=True, help="Output directory path to save model checkpoints.")
+@click.option("--learning-rate", default=0.001, type=float, help="Learning rate.")
+@click.option("--loss-total-weight", required=True, type=float, help="Total weight parameter for the loss function.")
+@click.option("--gradient-accumulation", required=True, type=int, help="Gradient accumulation steps.")
+@click.option("--batch-size", default=4, type=int, help="Batch size.")
+@click.option("--max-seq-shift", default=5000, type=int, help="Shift augmentation.")
+@click.option("--gradient-clipping", default=0.0, type=float, help="Gradient clipping.")
+@click.option("--save-top-k", default=1, type=int, help="Number of checkpoints to save.")
+@click.option("--epochs", default=1, type=int, help="Number of epochs.")
+@click.option("--logger", default="wandb", type=str, help="Logger.")
+@click.option("--num-workers", default=16, type=int, help="Number of workers.")
+@click.option("--seed", default=0, type=int, help="Random seed.")
+def cli_finetune(name, model, matrix_file, h5_file , outdir, learning_rate, loss_total_weight, gradient_accumulation, batch_size, max_seq_shift, gradient_clipping, save_top_k, epochs, logger, num_workers, seed):
     """Finetune the Decima model."""
-    wandb.login(host="https://genentech.wandb.io")
-    run = wandb.init(project="decima", dir=name, name=name)
-
-    matrix_file = os.path.join(dir, "aggregated.h5ad")
-    h5_file = os.path.join(dir, "data.h5")
-    print(f"Data paths: {matrix_file}, {h5_file}")
-
-    print("Reading anndata")
+    train_logger = logger
+    logger = logging.getLogger("decima")
+    logger.info(f"Data paths: matrix_file={matrix_file}, h5_file={h5_file}")
+    logger.info("Reading anndata")
     ad = anndata.read_h5ad(matrix_file)
 
-    print("Making dataset objects")
+    logger.info("Making dataset objects")
     train_dataset = HDF5Dataset(
         h5_file=h5_file,
         ad=ad,
         key="train",
-        max_seq_shift=5000,
+        max_seq_shift=max_seq_shift,
         augment_mode="random",
-        seed=0,
+        seed=seed,
     )
     val_dataset = HDF5Dataset(h5_file=h5_file, ad=ad, key="val", max_seq_shift=0)
 
     train_params = {
-        "optimizer": "adam",
-        "batch_size": bs,
-        "num_workers": 16,
+        "name": name,
+        "batch_size": batch_size,
+        "num_workers": num_workers,
         "devices": 0,
-        "logger": "wandb",
-        "save_dir": dir,
-        "max_epochs": 15,
-        "lr": lr,
-        "total_weight": weight,
-        "accumulate_grad_batches": grad,
+        "logger": train_logger,
+        "save_dir": outdir,
+        "max_epochs": epochs,
+        "lr": learning_rate,
+        "total_weight": loss_total_weight,
+        "accumulate_grad_batches": gradient_accumulation,
         "loss": "poisson_multinomial",
-        "pairs": ad.uns["disease_pairs"].values,
+        # "pairs": ad.uns["disease_pairs"].values,
+        "clip": gradient_clipping,
+        "save_top_k": save_top_k,
+        "pin_memory": True,
     }
     model_params = {
         "n_tasks": ad.shape[0],
-        "replicate": replicate,
+        "replicate": model,
     }
-    print(f"train_params: {train_params}")
-    print(f"model_params: {model_params}")
+    logger.info(f"train_params: {train_params}")
+    logger.info(f"model_params: {model_params}")
 
-    print("Initializing model")
+    logger.info("Initializing model")
     model = LightningModel(model_params=model_params, train_params=train_params)
 
-    print("Training")
+    logger.info("Training")
+    if logger == "wandb":
+        wandb.login(host="https://genentech.wandb.io")
+        run = wandb.init(project="decima", dir=name, name=name)
     model.train_on_dataset(train_dataset, val_dataset)
     train_dataset.close()
     val_dataset.close()
-    run.finish()
+    if logger == "wandb":
+        run.finish()

src/decima/cli/predict_genes.py

@@ -1,73 +1,67 @@
-"""Make predictions for all genes using an HDF5 file created by Decima's ``write_hdf5.py``."""
-
-import os
 import click
-import anndata
-import numpy as np
-import torch
-from decima.constants import DECIMA_CONTEXT_SIZE
-from decima.model.lightning import LightningModel
-from decima.data.read_hdf5 import list_genes
-from decima.data.dataset import HDF5Dataset
-
-# TODO: input can be just a h5ad file rather than a combination of h5 and matrix file.
+from decima.tools.inference import predict_gene_expression
 
 
 @click.command()
-@click.option("--device", type=int, help="Which GPU to use.")
-@click.option("--ckpts", multiple=True, required=True, help="Path to the model checkpoint(s).")
-@click.option("--h5_file", required=True, help="Path to h5 file indexed by genes.")
-@click.option("--matrix_file", required=True, help="Path to h5ad file containing genes to predict.")
-@click.option("--out_file", required=True, help="Output file path.")
+@click.option("-o", "--output", type=click.Path(), help="Path to the output h5ad file.")
+@click.option(
+    "--genes",
+    type=str,
+    default=None,
+    help="List of genes to predict. Default: None (all genes). If provided, only these genes will be predicted.",
+)
+@click.option(
+    "-m",
+    "--model",
+    type=str,
+    default="ensemble",
+    help="Path to the model checkpoint: `0`, `1`, `2`, `3`, `ensemble` or `path/to/model.ckpt`.",
+)
+@click.option(
+    "--metadata",
+    type=click.Path(exists=True),
+    default=None,
+    help="Path to the metadata anndata file. Default: None.",
+)
+@click.option(
+    "--device",
+    type=str,
+    default=None,
+    help="Device to use. Default: None which automatically selects the best device.",
+)
+@click.option("--batch-size", type=int, default=8, help="Batch size for the model. Default: 8")
+@click.option("--num-workers", type=int, default=4, help="Number of workers for the loader. Default: 4")
 @click.option("--max_seq_shift", default=0, help="Maximum jitter for augmentation.")
-def cli_predict_genes(device, ckpts, h5_file, matrix_file, out_file, max_seq_shift):
-    """Make predictions for all genes."""
-    torch.set_float32_matmul_precision("medium")
-
-    # TODO: device is unused, set the device appropriately
-    os.environ["CUDA_VISIBLE_DEVICES"] = str(device)
-    device = torch.device(0)
+@click.option("--genome", type=str, default="hg38", help="Genome build. Default: hg38.")
+@click.option(
+    "--save-replicates",
+    is_flag=True,
+    help="Save the replicates in the output parquet file. Default: False.",
+)
+def cli_predict_genes(
+    output, genes, model, metadata, device, batch_size, num_workers, max_seq_shift, genome, save_replicates
+):
+    if model in ["0", "1", "2", "3"]:
+        model = int(model)
 
-    print("Loading anndata")
-    ad = anndata.read_h5ad(matrix_file)
-    assert np.all(list_genes(h5_file, key=None) == ad.var_names.tolist())
-
-    print("Making dataset")
-    ds = HDF5Dataset(
-        key=None,
-        h5_file=h5_file,
-        ad=ad,
-        seq_len=DECIMA_CONTEXT_SIZE,
-        max_seq_shift=max_seq_shift,
-    )
+    if isinstance(device, str) and device.isdigit():
+        device = int(device)
 
-    print("Loading models from checkpoint")
-    models = [LightningModel.load_from_checkpoint(f).eval() for f in ckpts]
+    if genes is not None:
+        genes = genes.split(",")
 
-    print("Computing predictions")
-    preds = (
-        np.stack([model.predict_on_dataset(ds, devices=0, batch_size=6, num_workers=16) for model in models]).mean(0).T
-    )
-    ad.layers["preds"] = preds
+    if save_replicates and (model != "ensemble"):
+        raise ValueError("`--save-replicates` is only supported for ensemble model (`--model ensemble`).")
 
-    print("Computing correlations per gene")
-    ad.var["pearson"] = [np.corrcoef(ad.X[:, i], ad.layers["preds"][:, i])[0, 1] for i in range(ad.shape[1])]
-    ad.var["size_factor_pearson"] = [np.corrcoef(ad.X[:, i], ad.obs["size_factor"])[0, 1] for i in range(ad.shape[1])]
-    print(
-        f"Mean Pearson Correlation per gene: True: {ad.var.pearson.mean().round(2)} Size Factor: {ad.var.size_factor_pearson.mean().round(2)}"
+    ad = predict_gene_expression(
+        genes=genes,
+        model=model,
+        metadata_anndata=metadata,
+        device=device,
+        batch_size=batch_size,
+        num_workers=num_workers,
+        max_seq_shift=max_seq_shift,
+        genome=genome,
+        save_replicates=save_replicates,
     )
-
-    print("Computing correlation per track")
-    for dataset in ad.var.dataset.unique():
-        key = f"{dataset}_pearson"
-        ad.obs[key] = [
-            np.corrcoef(
-                ad[i, ad.var.dataset == dataset].X,
-                ad[i, ad.var.dataset == dataset].layers["preds"],
-            )[0, 1]
-            for i in range(ad.shape[0])
-        ]
-        print(f"Mean Pearson Correlation per pseudobulk over {dataset} genes: {ad.obs[key].mean().round(2)}")
-
-    print("Saved")
-    ad.write_h5ad(out_file)
+    ad.write_h5ad(output)

src/decima/core/result.py

@@ -157,7 +157,27 @@ def predicted_expression_matrix(self, genes: Optional[List[str]] = None) -> pd.D
         else:
             return pd.DataFrame(self.anndata[:, genes].layers["preds"], index=self.cells, columns=genes)
 
-    def prepare_one_hot(self, gene: str, variants: Optional[List[Dict]] = None) -> torch.Tensor:
+    def _pad_gene_metadata(self, gene_meta: pd.Series, padding: int = 0) -> pd.Series:
+        """
+        Pad gene metadata with padding.
+
+        Args:
+            gene_meta: Gene metadata
+            padding: Padding to add to the gene metadata
+
+        Returns:
+            pd.Series: Padded gene metadata
+        """
+        gene_meta = gene_meta.copy()
+        gene_meta["start"] = gene_meta["start"] - padding
+        gene_meta["end"] = gene_meta["end"] + padding
+        gene_meta["gene_start"] = gene_meta["gene_start"] - padding
+        gene_meta["gene_end"] = gene_meta["gene_end"] + padding
+        gene_meta["gene_mask_start"] = gene_meta["gene_mask_start"] - padding
+        gene_meta["gene_mask_end"] = gene_meta["gene_mask_end"] - padding
+        return gene_meta
+
+    def prepare_one_hot(self, gene: str, variants: Optional[List[Dict]] = None, padding: int = 0) -> torch.Tensor:
         """Prepare one-hot encoding for a gene.
 
         Args:
@@ -167,15 +187,15 @@ def prepare_one_hot(self, gene: str, variants: Optional[List[Dict]] = None) -> t
             torch.Tensor: One-hot encoding of the gene
         """
         assert gene in self.genes, f"{gene} is not in the anndata object"
-        gene_meta = self.gene_metadata.loc[gene]
+        gene_meta = self._pad_gene_metadata(self.gene_metadata.loc[gene], padding)
 
         if variants is None:
             seq = intervals_to_strings(gene_meta, genome="hg38")
             gene_start, gene_end = gene_meta.gene_mask_start, gene_meta.gene_mask_end
         else:
             seq, (gene_start, gene_end) = prepare_seq_alt_allele(gene_meta, variants)
 
-        mask = np.zeros(shape=(1, DECIMA_CONTEXT_SIZE))
+        mask = np.zeros(shape=(1, DECIMA_CONTEXT_SIZE + padding * 2))
         mask[0, gene_start:gene_end] += 1
         mask = torch.from_numpy(mask).float()