Merge branch 'main' of https://github.com/griffithlab/CIVIC_SVI_Course into main

Author: jhudsl-robot

docs/02-somatic_concepts.md

@@ -51,7 +51,7 @@ Single nucleotide variants (SNVs) are a change of a single nucleotide in DNA, an
 
 Small insertions and deletions (indels) are the second most common form of mutation found both in tumors, and occurring as germline variation in the human population. Indels are usually considered to be insertions and deletions of 50 base pairs or less. In protein coding regions, indels can generate in-frame changes to the amino acid structure of a protein when the insertion or deletion is a multiple of three base pairs, resulting in the addition or loss of one amino acid per three base pairs but preserving the coding frame of downstream bases. Indels can also result in frameshift mutations when the insertion or deletion in a coding region is not a multiple of three. These mutations alter the reading frame, resulting in a radical change to the amino acid sequence downstream of the mutation, usually resulting in protein termination and a non-functional protein product.  
 
-Translocations and fusions are a relatively common variant type found in cancer. Translocations are exchanges of large regions of DNA between different chromosomes, or between different regions of the same chromosome. Translocations may have breakpoints that occur in the middle of two different genes, resulting in fusions that have exons from both genes. A well known fusion results from the Philadelphia Chromosome, first identified in 1973 [@Rowley1973], which forms when chromosome 9 and chromosome 22 break and exchange large regions. This results in a fusion protein consisting of parts of the BCR gene and the ABL1 kinase gene, including the active kinase domain. The presence of BCR causes tetramer formation, which in turn activates the ABL1 kinase in a disregulated manner, driving oncogenic tyrosine kinase signaling. This fusion drives Chronic myeloid leukemia (CML) and is a driver that occurs in other cancer types as well. Targeted therapies against BCR::ABL1, such as imatinib, have been developed as a result of the discovery of this fusion and its driver properties [@Mughal2016]. 
+Translocations and fusions are a relatively common variant type found in cancer. Translocations are exchanges of large regions of DNA between different chromosomes, or between different regions of the same chromosome. Translocations may have breakpoints that occur in the middle of two different genes, resulting in fusions that have exons from both genes. A well known fusion results from the Philadelphia Chromosome [@Rowley1973], which forms when chromosome 9 and chromosome 22 break and exchange large regions. This results in a fusion protein consisting of parts of the BCR gene and the ABL1 kinase gene, including the active kinase domain. The presence of BCR causes tetramer formation, which in turn activates the ABL1 kinase in a disregulated manner, driving oncogenic tyrosine kinase signaling. This fusion drives Chronic myeloid leukemia (CML) and is a driver that occurs in other cancer types as well. Targeted therapies against BCR::ABL1, such as imatinib, have been developed as a result of the discovery of this fusion and its driver properties [@Mughal2016]. 
 
 A different type of genomic variant consists of copy number variants (CNVs) or copy neutral loss of heterogeneity (CNLOH). Copy number variants consist of losses or gains of large regions of chromosomes. Losses are usually deletions of genomic regions, and gains are usually two or larger fold duplications of genomic regions. These sorts of variants effect large numbers of genes and play a role in cancer. CNLOH usually results from the replacement of a large stretch of DNA on a chromosome with the same stretch of DNA derived from the homologous chromosome in the same cell. This causes a loss of heterozygosity as all DNA in this region is now identical between both homologous chromosomes, but there is no change in copy number of the genes in this region since there were no losses or gains in the DNA of this region. 
 

docs/index.html

@@ -195,7 +195,7 @@ <h1 class="title">Introduction to Clinical Interpretation of Somatic Cancer Vari
 </div>
 <div id="about-this-course" class="section level1 unnumbered">
 <h1>About this Course</h1>
-<p>This course is part of a series of courses for the <a href="https://itcr.cancer.gov/">Informatics Technology for Cancer Research (ITCR)</a> called the Informatics Technology for Cancer Research Education Resource. This material was created by the ITCR funded <a href="https://civicdb.org">CIViC resource</a>. This initiative is funded by the following grant: <a href="https://www.cancer.gov/">National Cancer Institute (NCI)</a> U24CA237719.</p>
+<p>This course is part of a series of courses for the <a href="https://itcr.cancer.gov/">Informatics Technology for Cancer Research (ITCR)</a> called the Informatics Technology for Cancer Research Education Resource. You can visit the bookdown rendered course material here at <a href="https://course.civicdb.org/">course.civicdb.org</a> or as a <a href="https://leanpub.com/c/introcivic">leanpub course</a>. This material was created by the ITCR funded <a href="https://civicdb.org">CIViC resource</a>. This initiative is funded by the following grant: <a href="https://www.cancer.gov/">National Cancer Institute (NCI)</a> U24CA237719.</p>
 
 </div>
 <hr>

docs/index.md

@@ -15,4 +15,4 @@ favicon: assets/ITN_favicon.ico
 
 # About this Course {-}
 
-This course is part of a series of courses for the [Informatics Technology for Cancer Research (ITCR)](https://itcr.cancer.gov/) called the Informatics Technology for Cancer Research Education Resource. This material was created by the ITCR funded [CIViC resource](https://civicdb.org). This initiative is funded by the following grant:  [National Cancer Institute (NCI)](https://www.cancer.gov/) U24CA237719.
+This course is part of a series of courses for the [Informatics Technology for Cancer Research (ITCR)](https://itcr.cancer.gov/) called the Informatics Technology for Cancer Research Education Resource. You can visit the bookdown rendered course material here at [course.civicdb.org](https://course.civicdb.org/) or as a [leanpub course](https://leanpub.com/c/introcivic). This material was created by the ITCR funded [CIViC resource](https://civicdb.org). This initiative is funded by the following grant:  [National Cancer Institute (NCI)](https://www.cancer.gov/) U24CA237719.

docs/introduction-to-somatic-variants.html

@@ -228,7 +228,7 @@ <h2><span class="header-section-number">2.4</span> Common Variant Types</h2>
 <p>The variant types usually encountered when sequencing tumors are listed below.</p>
 <p>Single nucleotide variants (SNVs) are a change of a single nucleotide in DNA, and are the most common variant found. In cancer, tumor (somatic) SNVs are best detected in comparison to a sample of germline DNA obtained using normal tissue from the same patient. SNVs are also present as natural variation in the germline among individuals and different human populations. Common germline variation is considered to be at a rate of approximately 1% or higher. In protein coding regions, SNVs can result in silent, missense, or nonsense mutations. Silent mutations alter the codon in a way that results in the same amino acid being produced (e.g. CCA and CCG both result in Proline). These mutations usually do not effect cell behavior unless the altered region has a secondary regulatory function. Missense mutations are changes in protein structure that replace one amino acid with another. These mutations are usually denoted with the notation A123B, where A is the original amino acid, 123 is the position of the amino acid in the protein, and B is the new amino acid change. The consequences of missense mutations range from minimal passenger mutations to oncogenic driver mutations (e.g. EGFR L858R). Missense mutations may also introduce premature stop codons (e.g. TGC -&gt; TGA). This results in a nonsense mutation. The consequences of nonsense mutations are usually a large or complete loss of protein function, as all parts of the protein downstream of the premature stop are no longer translated.</p>
 <p>Small insertions and deletions (indels) are the second most common form of mutation found both in tumors, and occurring as germline variation in the human population. Indels are usually considered to be insertions and deletions of 50 base pairs or less. In protein coding regions, indels can generate in-frame changes to the amino acid structure of a protein when the insertion or deletion is a multiple of three base pairs, resulting in the addition or loss of one amino acid per three base pairs but preserving the coding frame of downstream bases. Indels can also result in frameshift mutations when the insertion or deletion in a coding region is not a multiple of three. These mutations alter the reading frame, resulting in a radical change to the amino acid sequence downstream of the mutation, usually resulting in protein termination and a non-functional protein product.</p>
-<p>Translocations and fusions are a relatively common variant type found in cancer. Translocations are exchanges of large regions of DNA between different chromosomes, or between different regions of the same chromosome. Translocations may have breakpoints that occur in the middle of two different genes, resulting in fusions that have exons from both genes. A well known fusion results from the Philadelphia Chromosome, first identified in 1973 <span class="citation">(<a href="#ref-Rowley1973" role="doc-biblioref">ROWLEY 1973</a>)</span>, which forms when chromosome 9 and chromosome 22 break and exchange large regions. This results in a fusion protein consisting of parts of the BCR gene and the ABL1 kinase gene, including the active kinase domain. The presence of BCR causes tetramer formation, which in turn activates the ABL1 kinase in a disregulated manner, driving oncogenic tyrosine kinase signaling. This fusion drives Chronic myeloid leukemia (CML) and is a driver that occurs in other cancer types as well. Targeted therapies against BCR::ABL1, such as imatinib, have been developed as a result of the discovery of this fusion and its driver properties <span class="citation">(<a href="#ref-Mughal2016" role="doc-biblioref">Mughal et al. 2016</a>)</span>.</p>
+<p>Translocations and fusions are a relatively common variant type found in cancer. Translocations are exchanges of large regions of DNA between different chromosomes, or between different regions of the same chromosome. Translocations may have breakpoints that occur in the middle of two different genes, resulting in fusions that have exons from both genes. A well known fusion results from the Philadelphia Chromosome <span class="citation">(<a href="#ref-Rowley1973" role="doc-biblioref">Rowley 1973</a>)</span>, which forms when chromosome 9 and chromosome 22 break and exchange large regions. This results in a fusion protein consisting of parts of the BCR gene and the ABL1 kinase gene, including the active kinase domain. The presence of BCR causes tetramer formation, which in turn activates the ABL1 kinase in a disregulated manner, driving oncogenic tyrosine kinase signaling. This fusion drives Chronic myeloid leukemia (CML) and is a driver that occurs in other cancer types as well. Targeted therapies against BCR::ABL1, such as imatinib, have been developed as a result of the discovery of this fusion and its driver properties <span class="citation">(<a href="#ref-Mughal2016" role="doc-biblioref">Mughal et al. 2016</a>)</span>.</p>
 <p>A different type of genomic variant consists of copy number variants (CNVs) or copy neutral loss of heterogeneity (CNLOH). Copy number variants consist of losses or gains of large regions of chromosomes. Losses are usually deletions of genomic regions, and gains are usually two or larger fold duplications of genomic regions. These sorts of variants effect large numbers of genes and play a role in cancer. CNLOH usually results from the replacement of a large stretch of DNA on a chromosome with the same stretch of DNA derived from the homologous chromosome in the same cell. This causes a loss of heterozygosity as all DNA in this region is now identical between both homologous chromosomes, but there is no change in copy number of the genes in this region since there were no losses or gains in the DNA of this region.</p>
 </div>
 <div id="variant-representation-and-classification" class="section level2" number="2.5">
@@ -257,7 +257,7 @@ <h3> References</h3>
 Mughal, T. I., J. P. Radich, M. W. Deininger, J. F. Apperley, T. P. Hughes, C. J. Harrison, C. Gambacorti-Passerini, G. Saglio, J. Cortes, and G. Q. Daley. 2016. <span>“Chronic Myeloid Leukemia: Reminiscences and Dreams.”</span> <em>Haematologica</em> 101 (5): 541–58. <a href="https://doi.org/10.3324/haematol.2015.139337">https://doi.org/10.3324/haematol.2015.139337</a>.
 </div>
 <div id="ref-Rowley1973" class="csl-entry">
-ROWLEY, JANET D. 1973. <span>“A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia Identified by Quinacrine Fluorescence and Giemsa Staining.”</span> <em>Nature</em> 243 (5405): 290–93. <a href="https://doi.org/10.1038/243290a0">https://doi.org/10.1038/243290a0</a>.
+Rowley, Janet D. 1973. <span>“A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia Identified by Quinacrine Fluorescence and Giemsa Staining.”</span> <em>Nature</em> 243 (5405): 290–93. <a href="https://doi.org/10.1038/243290a0">https://doi.org/10.1038/243290a0</a>.
 </div>
 <div id="ref-Tan2015" class="csl-entry">
 Tan, Adrian, Gonçalo R. Abecasis, and Hyun Min Kang. 2015. <span>“Unified Representation of Genetic Variants.”</span> <em>Bioinformatics</em> 31 (13): 2202–4. <a href="https://doi.org/10.1093/bioinformatics/btv112">https://doi.org/10.1093/bioinformatics/btv112</a>.

docs/no_toc/02-somatic_concepts.md

@@ -51,7 +51,7 @@ Single nucleotide variants (SNVs) are a change of a single nucleotide in DNA, an
 
 Small insertions and deletions (indels) are the second most common form of mutation found both in tumors, and occurring as germline variation in the human population. Indels are usually considered to be insertions and deletions of 50 base pairs or less. In protein coding regions, indels can generate in-frame changes to the amino acid structure of a protein when the insertion or deletion is a multiple of three base pairs, resulting in the addition or loss of one amino acid per three base pairs but preserving the coding frame of downstream bases. Indels can also result in frameshift mutations when the insertion or deletion in a coding region is not a multiple of three. These mutations alter the reading frame, resulting in a radical change to the amino acid sequence downstream of the mutation, usually resulting in protein termination and a non-functional protein product.  
 
-Translocations and fusions are a relatively common variant type found in cancer. Translocations are exchanges of large regions of DNA between different chromosomes, or between different regions of the same chromosome. Translocations may have breakpoints that occur in the middle of two different genes, resulting in fusions that have exons from both genes. A well known fusion results from the Philadelphia Chromosome, first identified in 1973 [@Rowley1973], which forms when chromosome 9 and chromosome 22 break and exchange large regions. This results in a fusion protein consisting of parts of the BCR gene and the ABL1 kinase gene, including the active kinase domain. The presence of BCR causes tetramer formation, which in turn activates the ABL1 kinase in a disregulated manner, driving oncogenic tyrosine kinase signaling. This fusion drives Chronic myeloid leukemia (CML) and is a driver that occurs in other cancer types as well. Targeted therapies against BCR::ABL1, such as imatinib, have been developed as a result of the discovery of this fusion and its driver properties [@Mughal2016]. 
+Translocations and fusions are a relatively common variant type found in cancer. Translocations are exchanges of large regions of DNA between different chromosomes, or between different regions of the same chromosome. Translocations may have breakpoints that occur in the middle of two different genes, resulting in fusions that have exons from both genes. A well known fusion results from the Philadelphia Chromosome [@Rowley1973], which forms when chromosome 9 and chromosome 22 break and exchange large regions. This results in a fusion protein consisting of parts of the BCR gene and the ABL1 kinase gene, including the active kinase domain. The presence of BCR causes tetramer formation, which in turn activates the ABL1 kinase in a disregulated manner, driving oncogenic tyrosine kinase signaling. This fusion drives Chronic myeloid leukemia (CML) and is a driver that occurs in other cancer types as well. Targeted therapies against BCR::ABL1, such as imatinib, have been developed as a result of the discovery of this fusion and its driver properties [@Mughal2016]. 
 
 A different type of genomic variant consists of copy number variants (CNVs) or copy neutral loss of heterogeneity (CNLOH). Copy number variants consist of losses or gains of large regions of chromosomes. Losses are usually deletions of genomic regions, and gains are usually two or larger fold duplications of genomic regions. These sorts of variants effect large numbers of genes and play a role in cancer. CNLOH usually results from the replacement of a large stretch of DNA on a chromosome with the same stretch of DNA derived from the homologous chromosome in the same cell. This causes a loss of heterozygosity as all DNA in this region is now identical between both homologous chromosomes, but there is no change in copy number of the genes in this region since there were no losses or gains in the DNA of this region. 
 

docs/no_toc/index.html

@@ -195,7 +195,7 @@ <h1 class="title">Introduction to Clinical Interpretation of Somatic Cancer Vari
 </div>
 <div id="about-this-course" class="section level1 unnumbered">
 <h1>About this Course</h1>
-<p>This course is part of a series of courses for the <a href="https://itcr.cancer.gov/">Informatics Technology for Cancer Research (ITCR)</a> called the Informatics Technology for Cancer Research Education Resource. This material was created by the ITCR funded <a href="https://civicdb.org">CIViC resource</a>. This initiative is funded by the following grant: <a href="https://www.cancer.gov/">National Cancer Institute (NCI)</a> U24CA237719.</p>
+<p>This course is part of a series of courses for the <a href="https://itcr.cancer.gov/">Informatics Technology for Cancer Research (ITCR)</a> called the Informatics Technology for Cancer Research Education Resource. You can visit the bookdown rendered course material here at <a href="https://course.civicdb.org/">course.civicdb.org</a> or as a <a href="https://leanpub.com/c/introcivic">leanpub course</a>. This material was created by the ITCR funded <a href="https://civicdb.org">CIViC resource</a>. This initiative is funded by the following grant: <a href="https://www.cancer.gov/">National Cancer Institute (NCI)</a> U24CA237719.</p>
 
 </div>
 <hr>

docs/no_toc/index.md

@@ -15,4 +15,4 @@ favicon: assets/ITN_favicon.ico
 
 # About this Course {-}
 
-This course is part of a series of courses for the [Informatics Technology for Cancer Research (ITCR)](https://itcr.cancer.gov/) called the Informatics Technology for Cancer Research Education Resource. This material was created by the ITCR funded [CIViC resource](https://civicdb.org). This initiative is funded by the following grant:  [National Cancer Institute (NCI)](https://www.cancer.gov/) U24CA237719.
+This course is part of a series of courses for the [Informatics Technology for Cancer Research (ITCR)](https://itcr.cancer.gov/) called the Informatics Technology for Cancer Research Education Resource. You can visit the bookdown rendered course material here at [course.civicdb.org](https://course.civicdb.org/) or as a [leanpub course](https://leanpub.com/c/introcivic). This material was created by the ITCR funded [CIViC resource](https://civicdb.org). This initiative is funded by the following grant:  [National Cancer Institute (NCI)](https://www.cancer.gov/) U24CA237719.