14023d97345829f14154773c87712ed9550a0638 abenetpa Wed Sep 16 08:17:42 2020 -0700 added validity track descriptions refs #24818 diff --git src/hg/makeDb/trackDb/human/clinGen.html src/hg/makeDb/trackDb/human/clinGen.html index 1d9f81e..641a3dc 100644 --- src/hg/makeDb/trackDb/human/clinGen.html +++ src/hg/makeDb/trackDb/human/clinGen.html @@ -21,111 +21,198 @@ No attempt to identify individual patients should be undertaken. No one is authorized to attempt to identify patients by any means. </p> </b> </div> <p> The <a target="_blank" href="https://clinicalgenome.org"><b>Clinical Genome Resource (ClinGen)</b></a> tracks display data generated from several key curation activities related to <a target="_blank" href="https://clinicalgenome.org/curation-activities/gene-disease-validity/"><b>gene-disease validity</b></a>, <a target="_blank" href="https://clinicalgenome.org/curation-activities/dosage-sensitivity/" ><b>dosage sensitivity</b></a>, and <a target="_blank" href="https://clinicalgenome.org/curation-activities/variant-pathogenicity/"><b>variant pathogenicity</b></a>. ClinGen is a <a target="_blank" -href="https://www.nih.gov/">National Institute of Health (NIH)</a>-funded program dedicated to building a -central resource that defines the clinical relevance of genes -and variants for use in precision medicine and research. This is accomplished by harnessing the data -from both research efforts and clinical genetic testing and using it to propel expert and machine-driven -curation activities. ClinGen works closely with the <a target="_blank" +href="https://www.nih.gov/">National Institute of Health (NIH)</a>-funded initiative dedicated to +identifying clinically relevant genes and variants for use in precision medicine and research. +This is accomplished by harnessing the data from both research efforts and clinical genetic +testing and using it to propel expert and machine-driven curation activities. +ClinGen works closely with the <a target="_blank" href="https://www.nlm.nih.gov/">National Center for Biotechnology Information (NCBI)</a> of the <a target="_blank" href="https://www.nlm.nih.gov/">National Library of Medicine (NLM)</a> which distributes part of this information through its <a target="_blank" href="https://www.ncbi.nlm.nih.gov/clinvar/">ClinVar</a> database. </p> <p> The available data tracks are: <ul> -<li><b>Clinical Genome Resource Dosage Sensitivity Map Haploinsufficiency (ClinGen -Haploinsufficiency) and Triplosensitivity (ClinGen Triplosensitivity)</b> - +<li><b>ClinGen Dosage Sensitivity Map -Haploinsufficiency (ClinGen +Haploinsufficiency) and -Triplosensitivity (ClinGen Triplosensitivity)</b> - Shows evidence supporting or refuting haploinsufficiency (loss) and triplosensitivity (gain) as mechanisms for disease at gene-level and larger genomic regions. </li> +<li><b>ClinGen Gene-Disease Validity Classification (ClinGen Validity)</b> - +Provides a semi qualitative measurement for the strength of evidence of a gene-disease relationship. +</li> </ul> </p> <p> A <b>rating system</b> is used to classify the <b>evidence</b> supporting or refuting dosage - sensitivity for individual genes and regions, which takes into consideration the following criteria: -number of causative mutations reported, patterns of inheritance, consistency of phenotype, evidence + sensitivity for individual genes and regions, which takes in consideration the following criteria: +number of causative variants reported, patterns of inheritance, consistency of phenotype, evidence from large-scale case-control studies, mutational mechanisms, data from public genome variation databases, and expert consensus opinion. </p> <p> The system is intended to be of a "dynamic nature", with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected is displayed within a publicly available -<a target="_blank" href="https://search.clinicalgenome.org/kb/gene-dosage">database</a>. +<a target="_blank" href="https://dosage.clinicalgenome.org/index.shtml">database</a>. Evidence that haploinsufficiency or triplosensitivity of a gene is associated with a specific -phenotype will aid in the interpretive assessment of CNVs including that gene. +phenotype will aid in the interpretive assessment of CNVs including that gene or genomic region. +</p> +<p> +Similarly, a <b>qualitative classification system</b> is used to correlate the <b>evidence</b> of +a gene-disease relationship: "Definitive", "Strong", "Moderate", "Limited", "Animal Model Only", +"No Known Disease Relationship", "Disputed", or "Refuted". </p> + <h2>Display Conventions</h2> <h3>Haploinsufficiency/Triplosensitivity tracks</h3> <p> +Items are shaded according to dosage sensitivity type, <b><font color="red">red</font></b> +for haploinsufficiency score 3, <b><font color="blue">blue</font></b> for triplosensitivity score 3, +and <B><font color="#a8a8a8">grey</font></b> for other evidence scores or + not yet evaluated). +Mouseover on items shows the supporting evidence of dosage sensitivity. +Tracks can be filtered according to the supporting evidence of dosage sensitivity. + +<p> <b>Dosage Scores</b> are used to classify the evidence of the supporting dosage sensitivity map: <dl> <dd><b>0</b> - no evidence available</dd> <dd><b>1</b> - little evidence for dosage pathogenicity</dd> <dd><b>2</b> - some evidence for dosage pathogenicity</dd> <dd><b>3</b> - sufficient evidence for dosage pathogenicity</dd> <dd><b>30</b> - gene associated with autosomal recessive phenotype</dd> <dd><b>40</b> - dosage sensitivity unlikely</dd> </dl> </p> + +<p> For more information on the use of the scores see the ClinGen <a target="_blank" href="https://clinicalgenome.org/tools/cnv-webinar/faq/">FAQs</a>. -Items are shaded according to dosage sensitivity type, <b><font color="red">red</font></b> -for haploinsufficiency, <b><font color="blue">blue</font></b> for triplosensitivity, -and <B><font color="#a8a8a8">grey</font></b> for other evidence scores or -for genes/regions that have not been evaluated yet or no evidence is available. A light to dark -gradient color is used according to the degree of supporting evidence. -</p> -<p> -Mouseover on items shows the supporting evidence of dosage sensitivity and respective scores. All -tracks can be filtered according to the supporting evidence of dosage sensitivity. -</p> +<p/> + +<H3>Gene-Disease Validity track</H3> + +<P> +The gene-disease validity classifications are labeled with the disease entity and hovering +over the features shows the associated gene. Items are color coded based on the strength of their +classification as provided below: +</P> +<table> + <thead> + <tr> + <th style="border-bottom: 2px solid #6678B1;">Color</th> + <th style="border-bottom: 2px solid #6678B1;">Classifications</th> + </tr> + </thead> + <tbody><tr> + <th bgcolor="#7800AA"></th> + <td align="left"><b>Definitive:</b> The role of this gene in this particular disease has been +repeatedly demonstrated and has been upheld over time</td> + </tr> + <tr> + <th bgcolor="#000066"></th> + <td align="left"><b>Strong:</b> The role of this gene in disease has been independently +demonstrated typically in at least two separate studies, including both strong variant-level +evidence in unrelated probands and compelling gene-level evidence from experimental data</td> + </tr> + <tr> + <th bgcolor="#0000FF"></th> + <td align="left"><b>Moderate:</b> There is moderate evidence to support a causal role for this +gene in this disease, typically including both several probands with variants and moderate +experimental data supporting the gene-disease assertion</td> + </tr> + <tr> + <th bgcolor="#9999FF"></th> + <td align="left"><b>Limited:</b> There is limited evidence to support a causal role for this +gene in this disease, such as few probands with variants and limited experimental data supporting +the gene-disease assertion</td> + </tr> + <tr> + <th bgcolor="#6E6E6E"></th> + <td align="left"><b>Animal Model Only:</b> There are no published human probands with variants +but there is animal model data supporting the gene-disease assertion</td> + </tr> + <tr> + <th bgcolor="#000000"></th> + <td align="left"><b>No Known Disease Relationship:</b> Evidence for a causal role in disease +has not been reported</td> + </tr> + <tr> + <th bgcolor="#FF9933"></th> + <td align="left"><b>Disputed:</b> Conflicting evidence disputing a role for this gene in this +disease has arisen since the initial report identifying an association between the gene and disease</td> + </tr> + <tr> + <th bgcolor="#FF3333"></th> + <td align="left"><b>Refuted:</b> Evidence refuting the role of the gene in the specified +disease has been reported and significantly outweighs any evidence supporting the role</td> + </tr> +</tbody></table> + +<P> +The version of the <b>ClinGen Standard Operating Procedures (SOPs)</b> that each gene-disease +classification was performed with is provided as well. An older or newer SOP version does not +necessarily mean the classification is any more or less valid but is provided for clarity. +Each details page also contains a direct link to an evidence summary detailing the rationale behind +the specific classification and information such as a breakdown of the semiquantitative framework, +relevant PubMed IDs, the type of data (Genetic vs Experimental Evidence), and a detailed summary. +</P> + <p> These tracks are multi-view composite tracks that contain multiple data types (views). Each view within a track has separate display controls, as described <a href="../goldenPath/help/multiView.html">here</a>. </p> <h2>Data Access</h2> <p> The raw data can be explored interactively with the <a href="../cgi-bin/hgTables">Table Browser</a>, or the <a href="../cgi-bin/hgIntegrator">Data Integrator</a>. For automated analysis, the data may be queried from our <a href="/goldenPath/help/api.html">REST API</a>. Please refer to our <a href="https://groups.google.com/a/soe.ucsc.edu/forum/#!forum/genome">mailing list archives</a> for questions, or our <a href="../FAQ/FAQdownloads.html#downloads36">Data Access FAQ</a> for more information. </p> +<p> +Data is also freely available on the ClinGen website +<a href="https://search.clinicalgenome.org/kb/gene-validity/" target="_BLANK">(gene-disease curation methods)</a> +and FTP <a href="https://ftp.clinicalgenome.org/" target="_BLANK">(dosage curations)</a>. +</p> + + <h2>Credits</h2> <p> -Thank you to ClinGen and NCBI, especially Erin Rooney Riggs for technical coordination and -consultation, and to Christopher Lee, Anna Benet-Pages, and Maximilian Haeussler of the Genome -Browser team for engineering the track display. +Thank you to ClinGen and NCBI, especially Erin Rooney Riggs, Christa Lese Martin, Tristan Nelson, + May Flowers, Scott Goehringer, and Phillip Weller for technical coordination and +consultation, and to Christopher Lee, and Anna Benet-Pages of the Genome +Browser team. </p> <h2>References</h2> <p> Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP, Landrum MJ, Ledbetter DH, Maglott DR, Martin CL, Nussbaum RL <em>et al</em>. <a href="https://www.ncbi.nlm.nih.gov/pubmed/26014595" target="_blank"> ClinGen--the Clinical Genome Resource</a>. <em>N Engl J Med</em>. 2015 Jun 4;372(23):2235-42. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/26014595" target="_blank">26014595</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474187/" target="_blank">PMC4474187</a> </p> <p>