CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase

Author:

Krysiak Kilannin1234ORCID,Danos Arpad M24,Saliba Jason4,McMichael Joshua F2,Coffman Adam C2ORCID,Kiwala Susanna2ORCID,Barnell Erica K2,Sheta Lana2,Grisdale Cameron J5,Kujan Lynzey2,Pema Shahil2,Lever Jake6,Ridd Sarah7,Spies Nicholas C2,Andric Veronica7,Chiorean Andreea7,Rieke Damian T8,Clark Kaitlin A2,Reisle Caralyn59,Venigalla Ajay C4,Evans Mark10,Jani Payal7,Takahashi Hideaki11,Suda Avila4,Horak Peter12,Ritter Deborah I13,Zhou Xin14ORCID,Ainscough Benjamin J2,Delong Sean15,Kesserwan Chimene16,Lamping Mario8,Shen Haolin4,Marr Alex R1,Hoang My H4,Singhal Kartik4,Khanfar Mariam4,Li Brian V2,Lin Wan-Hsin17,Terraf Panieh18,Corson Laura B19,Salama Yasser7,Campbell Katie M2ORCID,Farncombe Kirsten M20,Ji Jianling21ORCID,Zhao Xiaonan22,Xu Xinjie23,Kanagal-Shamanna Rashmi24,King Ian25,Cotto Kelsy C4ORCID,Skidmore Zachary L2,Walker Jason R2,Zhang Jinghui14,Milosavljevic Aleksandar22,Patel Ronak Y22,Giles Rachel H26,Kim Raymond H27,Schriml Lynn M28ORCID,Mardis Elaine R2930,Jones Steven J M5,Raca Gordana21,Rao Shruti31,Madhavan Subha31,Wagner Alex H2932ORCID,Griffith Malachi23433ORCID,Griffith Obi L23433ORCID

Affiliation:

1. Department of Pathology and Immunology, Washington University in St Louis School of Medicine , St. Louis, MO, USA

2. McDonnell Genome Institute, Washington University in St Louis School of Medicine , St. Louis, MO, USA

3. Siteman Cancer Center, Washington University in St Louis School of Medicine , St. Louis, MO, USA

4. Department of Medicine, Washington University in St Louis School of Medicine , St. Louis, MO, USA

5. Canada's Michael Smith Genome Sciences Centre , Vancouver, BC, Canada

6. School of Computer Science, University of Glasgow , Glasgow, UK

7. Department of Medicine, Division of Medical Oncology, University Health Network , Toronto, Ontario, Canada

8. Charité – Universitätsmedizin Berlin , corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany

9. Bioinformatics Graduate Program, Faculty of Science, University of British Columbia , Vancouver, BC, Canada

10. Caris Life Sciences , Phoenix, AZ, USA

11. Department of Experimental Therapeutics/Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East , Kashiwa, Japan

12. Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ) , Heidelberg, Germany

13. Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX, USA

14. Department of Computational Biology, St. Jude Children's Research Hospital , Memphis, TN, USA

15. Lassonde School of Engineering, York University , Toronto, Ontario, Canada

16. Department of Pathology, NYU Grossman School of Medicine , New York, NY, USA and Genetics Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, USA

17. Mayo Clinic Florida , Jacksonville, FL, USA

18. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center , New York, NY, USA

19. Dana-Farber/Boston Children's Cancer and Blood Disorders Center , Boston, MA, USA

20. Toronto General Hospital Research Institute, University Health Network , Toronto, Ontario, Canada

21. Children's Hospital Los Angeles, University of Southern California , Los Angeles, CA, USA

22. Department of Molecular and Human Genetics, Baylor College of Medicine , Houston, TX, USA

23. Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN, USA

24. Department of Hematopathology and Molecular Diagnostics, The University of Texas MD Anderson Cancer Center , Houston, TX, USA

25. Division of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network (UHN) , Toronto, ON, Canada

26. International Kidney Cancer Coalition , Duivendrecht-Amsterdam, the Netherlands

27. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Sinai Health System, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Ontario Institute for Cancer Research, Department of Medicine, University of Toronto , Toronto, Ontario, Canada

28. University of Maryland School of Medicine , Baltimore, MD, USA

29. The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital , Columbus, OH, USA

30. Departments of Pediatrics and Neurosurgery, The Ohio State University College of Medicine , Columbus, OH, USA

31. Innovation Center for Biomedical Informatics, Georgetown University Medical Center , WA DC, USA

32. Departments of Pediatrics and Biomedical Informatics, The Ohio State University College of Medicine , Columbus, OH, USA

33. Department of Genetics, Washington University in St Louis School of Medicine , St. Louis, MO, USA

Abstract

Abstract CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications.

Funder

NCI

Cancer Moonshot and Childhood Cancer Data Initiative

Washington University Institute of Clinical and Translational Sciences

National Center for Advancing Translational Sciences

National Institutes of Health

St. Louis Children's Hospital and Washington University School of Medicine

Google Big Query

Amazon Web Services Open Data

VHL Alliance Research

Starbucks Clinical Genetics/Genomics Research Studentship

Charité - Universitätsmedizin Berlin

Berlin Institute of Health

Clinical Genome Resource

NHGRI

Bhalwani Family Charitable Foundation

NIH

Publisher

Oxford University Press (OUP)

Subject

Genetics

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