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Grant Details

Grant Number: 5U01CA209936-03 Interpret this number
Primary Investigator: Griffith, Obi
Organization: Washington University
Project Title: Development of Informatics Resources for Interpretation of Clinically Actionable Variants in Cancer
Fiscal Year: 2018


Abstract

Abstract Clinical cancer sequencing will increasingly be used to identify genomic alterations that are relevant to understanding cancer progression and improving clinical decision making for individual patients. Currently, the most critical bottleneck in the precision medicine workflow is at the interpretation step. However, there are few resources to help with the prioritization and interpretation of these alterations in a clinical context. Multiple groups are building their own databases documenting clinical interpretation of tumor mutations as they are observed in those groups. This represents a largely redundant effort with no mechanisms for capturing evolving evidence from the biomedical literature. Public knowledgebases are needed with sophisticated application programming interfaces (APIs) that allow rapid intersection of genomic alterations with interpretations of their clinical actionability. The goal of this proposal is to develop such an expert-curated knowledgebase, web interface and API for Clinical Interpretation of Variants in Cancer (CIViC - www.civicdb.org). The knowledge created from this effort will be freely available and the product of open discussion across a diverse community. This will require an interdisciplinary approach to combine the expertise of genome scientists and cancer researchers, whose efforts are otherwise often isolated. Content will be created with transparency, kept current, be comprehensive, track provenance, and acknowledge the efforts of creators. It will cover all types of alterations from single nucleotide variants to structural variants, RNA fusions, expression changes, epigenetic alterations and others. The interface will capture both structured statements of evidence for actionability to allow computational data mining and also human-readable interpretations. Content and software will be unencumbered and easy to access to encourage both academic and commercial engagement. In order to achieve these goals CIViC will require well-designed data standards, use of structured vocabularies, and a user-friendly curation interface that balances data mining needs with human accessibility. Focused `hackathons' and curation meetings will be organized to establish community standards and coordinate with synergistic efforts by the Global Alliance for Genomics and Health (GA4GH) and ClinGen working groups. The CIViC resource will serve as the foundation for development of applications critical to widespread implementation of precision medicine for cancer. Specifically, it will facilitate rapid generation of targeted sequencing assays, automated clinical report generation, and other applications built upon the open CIViC standards and APIs.



Publications

Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas.
Authors: Mudianto T. , Campbell K.M. , Webb J. , Zolkind P. , Skidmore Z.L. , Riley R. , Barnell E.K. , Ozgenc I. , Giri T. , Dunn G.P. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2021-04-15; 27(8), p. 2326-2339.
EPub date: 2021-02-05.
PMID: 33547198
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Integration of the Drug-Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts.
Authors: Freshour S.L. , Kiwala S. , Cotto K.C. , Coffman A.C. , McMichael J.F. , Song J.J. , Griffith M. , Griffith O.L. , Wagner A.H. .
Source: Nucleic acids research, 2021-01-08; 49(D1), p. D1144-D1151.
PMID: 33237278
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Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.
Authors: Uppaluri R. , Campbell K.M. , Egloff A.M. , Zolkind P. , Skidmore Z.L. , Nussenbaum B. , Paniello R.C. , Rich J.T. , Jackson R. , Pipkorn P. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2020-10-01; 26(19), p. 5140-5152.
EPub date: 2020-07-14.
PMID: 32665297
Related Citations

Collaborative, Multidisciplinary Evaluation of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices.
Authors: Rao S. , Pitel B. , Wagner A.H. , Boca S.M. , McCoy M. , King I. , Gupta S. , Park B.H. , Warner J.L. , Chen J. , et al. .
Source: JCO clinical cancer informatics, 2020 07; 4, p. 602-613.
PMID: 32644817
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A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer.
Authors: Wagner A.H. , Walsh B. , Mayfield G. , Tamborero D. , Sonkin D. , Krysiak K. , Deu-Pons J. , Duren R.P. , Gao J. , McMurry J. , et al. .
Source: Nature genetics, 2020 04; 52(4), p. 448-457.
EPub date: 2020-04-03.
PMID: 32246132
Related Citations

Wikidata as a knowledge graph for the life sciences.
Authors: Waagmeester A. , Stupp G. , Burgstaller-Muehlbacher S. , Good B.M. , Griffith M. , Griffith O.L. , Hanspers K. , Hermjakob H. , Hudson T.S. , Hybiske K. , et al. .
Source: eLife, 2020-03-17; 9, .
EPub date: 2020-03-17.
PMID: 32180547
Related Citations

CIViCpy: A Python Software Development and Analysis Toolkit for the CIViC Knowledgebase.
Authors: Wagner A.H. , Kiwala S. , Coffman A.C. , McMichael J.F. , Cotto K.C. , Mooney T.B. , Barnell E.K. , Krysiak K. , Danos A.M. , Walker J. , et al. .
Source: JCO clinical cancer informatics, 2020 03; 4, p. 245-253.
PMID: 32191543
Related Citations

pVACtools: A Computational Toolkit to Identify and Visualize Cancer Neoantigens.
Authors: Hundal J. , Kiwala S. , McMichael J. , Miller C.A. , Xia H. , Wollam A.T. , Liu C.J. , Zhao S. , Feng Y.Y. , Graubert A.P. , et al. .
Source: Cancer immunology research, 2020 03; 8(3), p. 409-420.
EPub date: 2020-01-06.
PMID: 31907209
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Neoadjuvant PD-1 Immune Checkpoint Blockade Reverses Functional Immunodominance among Tumor Antigen-Specific T Cells.
Authors: Friedman J. , Moore E.C. , Zolkind P. , Robbins Y. , Clavijo P.E. , Sun L. , Greene S. , Morisada M.V. , Mydlarz W.K. , Schmitt N. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2020-02-01; 26(3), p. 679-689.
EPub date: 2019-10-23.
PMID: 31645352
Related Citations

Text-mining clinically relevant cancer biomarkers for curation into the CIViC database.
Authors: Lever J. , Jones M.R. , Danos A.M. , Krysiak K. , Bonakdar M. , Grewal J.K. , Culibrk L. , Griffith O.L. , Griffith M. , Jones S.J.M. .
Source: Genome medicine, 2019-12-03; 11(1), p. 78.
EPub date: 2019-12-03.
PMID: 31796060
Related Citations

Standard operating procedure for curation and clinical interpretation of variants in cancer.
Authors: Danos A.M. , Krysiak K. , Barnell E.K. , Coffman A.C. , McMichael J.F. , Kiwala S. , Spies N.C. , Sheta L.M. , Pema S.P. , Kujan L. , et al. .
Source: Genome medicine, 2019-11-29; 11(1), p. 76.
EPub date: 2019-11-29.
PMID: 31779674
Related Citations

A case for expert curation: an overview of cancer curation in the Clinical Genome Resource (ClinGen).
Authors: Ritter D.I. , Rao S. , Kulkarni S. , Madhavan S. , Offit K. , Plon S.E. .
Source: Cold Spring Harbor molecular case studies, 2019 10; 5(5), .
EPub date: 2019-10-23.
PMID: 31645350
Related Citations

Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes.
Authors: Barnell E.K. , Waalkes A. , Mosior M.C. , Penewit K. , Cotto K.C. , Danos A.M. , Sheta L.M. , Campbell K.M. , Krysiak K. , Rieke D. , et al. .
Source: JCO clinical cancer informatics, 2019 10; 3, p. 1-12.
PMID: 31618044
Related Citations

Noninvasive Detection of High-Risk Adenomas Using Stool-Derived Eukaryotic RNA Sequences as Biomarkers.
Authors: Barnell E.K. , Kang Y. , Wurtzler E.M. , Griffith M. , Chaudhuri A.A. , Griffith O.L. , Geneoscopy Scientists .
Source: Gastroenterology, 2019 09; 157(3), p. 884-887.e3.
EPub date: 2019-05-30.
PMID: 31154021
Related Citations

Best practices for bioinformatic characterization of neoantigens for clinical utility.
Authors: Richters M.M. , Xia H. , Campbell K.M. , Gillanders W.E. , Griffith O.L. , Griffith M. .
Source: Genome medicine, 2019-08-28; 11(1), p. 56.
EPub date: 2019-08-28.
PMID: 31462330
Related Citations

A Spontaneous Aggressive ERĪ±+ Mammary Tumor Model Is Driven by Kras Activation.
Authors: Campbell K.M. , O'Leary K.A. , Rugowski D.E. , Mulligan W.A. , Barnell E.K. , Skidmore Z.L. , Krysiak K. , Griffith M. , Schuler L.A. , Griffith O.L. .
Source: Cell reports, 2019-08-06; 28(6), p. 1526-1537.e4.
PMID: 31390566
Related Citations

Standard operating procedure for somatic variant refinement of sequencing data with paired tumor andĀ normal samples.
Authors: Barnell E.K. , Ronning P. , Campbell K.M. , Krysiak K. , Ainscough B.J. , Sheta L.M. , Pema S.P. , Schmidt A.D. , Richters M. , Cotto K.C. , et al. .
Source: Genetics in medicine : official journal of the American College of Medical Genetics, 2019 04; 21(4), p. 972-981.
EPub date: 2018-10-05.
PMID: 30287923
Related Citations

Accounting for proximal variants improves neoantigen prediction.
Authors: Hundal J. , Kiwala S. , Feng Y.Y. , Liu C.J. , Govindan R. , Chapman W.C. , Uppaluri R. , Swamidass S.J. , Griffith O.L. , Mardis E.R. , et al. .
Source: Nature genetics, 2019 01; 51(1), p. 175-179.
EPub date: 2018-12-03.
PMID: 30510237
Related Citations

A deep learning approach to automate refinement of somatic variant calling from cancer sequencing data.
Authors: Ainscough B.J. , Barnell E.K. , Ronning P. , Campbell K.M. , Wagner A.H. , Fehniger T.A. , Dunn G.P. , Uppaluri R. , Govindan R. , Rohan T.E. , et al. .
Source: Nature genetics, 2018 12; 50(12), p. 1735-1743.
EPub date: 2018-11-05.
PMID: 30397337
Related Citations

Adapting crowdsourced clinical cancer curation in CIViC to the ClinGen minimum variant level data community-driven standards.
Authors: Danos A.M. , Ritter D.I. , Wagner A.H. , Krysiak K. , Sonkin D. , Micheel C. , McCoy M. , Rao S. , Raca G. , Boca S.M. , et al. .
Source: Human mutation, 2018 11; 39(11), p. 1721-1732.
PMID: 30311370
Related Citations

The prognostic effects of somatic mutations in ER-positive breast cancer.
Authors: Griffith O.L. , Spies N.C. , Anurag M. , Griffith M. , Luo J. , Tu D. , Yeo B. , Kunisaki J. , Miller C.A. , Krysiak K. , et al. .
Source: Nature communications, 2018-09-04; 9(1), p. 3476.
EPub date: 2018-09-04.
PMID: 30181556
Related Citations

Oral Cavity Squamous Cell Carcinoma Xenografts Retain Complex Genotypes and Intertumor Molecular Heterogeneity.
Authors: Campbell K.M. , Lin T. , Zolkind P. , Barnell E.K. , Skidmore Z.L. , Winkler A.E. , Law J.H. , Mardis E.R. , Wartman L.D. , Adkins D.R. , et al. .
Source: Cell reports, 2018-08-21; 24(8), p. 2167-2178.
PMID: 30134176
Related Citations

DGIdb 3.0: a redesign and expansion of the drug-gene interaction database.
Authors: Cotto K.C. , Wagner A.H. , Feng Y.Y. , Kiwala S. , Coffman A.C. , Spies G. , Wollam A. , Spies N.C. , Griffith O.L. , Griffith M. .
Source: Nucleic acids research, 2018-01-04; 46(D1), p. D1068-D1073.
PMID: 29156001
Related Citations

Standardizing And Democratizing Access To Cancer Molecular Diagnostic Test Data From Patients To Drive Translational Research.
Authors: Madhavan S. , Ritter D. , Micheel C. , Rao S. , Roy A. , Sonkin D. , Mccoy M. , Griffith M. , Griffith O.L. , Mcgarvey P. , et al. .
Source: AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science, 2018; 2017, p. 152-159.
EPub date: 2018-05-18.
PMID: 29888062
Related Citations

ClinGen Cancer Somatic Working Group - standardizing and democratizing access to cancer molecular diagnostic data to drive translational research.
Authors: Madhavan S. , Ritter D. , Micheel C. , Rao S. , Roy A. , Sonkin D. , Mccoy M. , Griffith M. , Griffith O.L. , Mcgarvey P. , et al. .
Source: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing, 2018; 23, p. 247-258.
PMID: 29218886
Related Citations

Clinical implications of neoepitope landscapes for adult and pediatric cancers.
Authors: Feng Y.Y. , Griffith O.L. , Griffith M. .
Source: Genome medicine, 2017-08-31; 9(1), p. 77.
EPub date: 2017-08-31.
PMID: 28854952
Related Citations

CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer.
Authors: Griffith M. , Spies N.C. , Krysiak K. , McMichael J.F. , Coffman A.C. , Danos A.M. , Ainscough B.J. , Ramirez C.A. , Rieke D.T. , Kujan L. , et al. .
Source: Nature genetics, 2017-01-31; 49(2), p. 170-174.
PMID: 28138153
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