Abstract 1194: Redesigning CIViC: Enhancing the structured curation of complex cancer variant data
Authors: Krysiak Kilannin C. , Coffman Adam C. , Kiwala Susanna , McMichael Joshua F. , Danos Arpad M. , Saliba Jason , Grisdale Cameron J. , Lever Jake , Sheta Lana , Rao Shruti , Wagner Alex H. , Griffith Malachi , Griffith Obi L. 
Published: June 2022

Abstract
The Clinical Interpretation of Variants in Cancer (CIViC; www.civicdb.org) knowledgebase is a curation platform designed to capture evidence from the published literature which support or refute the significance of genomic variants in various cancer types. Since the launch of the beta user interface in 2014, this knowledgebase has undergone substantial evolution and redesign to support the needs of the clinical and research communities. Significant work has been done by the community to release guidelines and resources to support cancer variant interpretation. CIViC is a crowd sourced, expert moderated resource with a community of over 300 active curators. In response to community feedback, evolving guidelines and improved understanding of the genetics of cancer, we have developed CIViC 2.0, a major redesign that expands the capabilities of this widely used resource.
CIViC 2.0 has been designed to support complex variant relationships (termed molecular profiles in CIViC) such as the poor prognostic impact of the combination of variants in FLT3, DNMT3A and NPM1 in acute myeloid leukemia. These highly structured molecular profiles link details about each constituent variant, including genomic coordinates, HGVS, aliases, and additional metadata. Molecular profiles will also support the absence of a variant, which has become critical in targeted therapy decision making such as colorectal cancer where EGFR expression without a KRAS variant is an indication for targeted inhibitor therapy. These molecular profiles also support structural variants. While fusions have always been supported, CIViC 2.0 will support complex genomic coordinate or cytoband specific queries.
Significant technical changes have improved the speed and performance of the UI and the underlying API. A complete redesign of the API, utilizing GraphQL, empowers users to ask more complex questions and more deeply explore this highly curated data. More robust data schemas and comprehensive validation of evidence structure will allow for the programmatic submission of new evidence. By utilizing site-wide full text faceted search, identifying relevant content in summaries, evidence items, or even curator comments is straightforward.
The CIViC 2.0 redesign supports the ever-increasing complexity of cancer variant information and provides a powerful tool to explore and utilize the carefully curated data within the knowledgebase for a multitude of questions related to basic, translational, and clinical research.
Citation Format: Kilannin C. Krysiak, Adam C. Coffman, Susanna Kiwala, Joshua F. McMichael, Arpad M. Danos, Jason Saliba, Cameron J. Grisdale, Jake Lever, Lana Sheta, Shruti Rao, Alex H. Wagner, Malachi Griffith, Obi L. Griffith. Redesigning CIViC: Enhancing the structured curation of complex cancer variant data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1194.