Abstract 1156: Genome Nexus: A comprehensive resource for the annotation and interpretation of genomic variants in cancer

Abstract

Abstract Interpreting genomic variants in tumor samples presents a challenge in research and the clinical setting. A major barrier is that information about variants is fragmented across disparate databases, and aggregating information from these requires building extensive infrastructure. To this end, we have developed Genome Nexus, a one stop shop for variant annotation, equipped with a powerful API for bulk annotation of variants and a user friendly interface for cancer researchers. Genome Nexus is available at https://www.genomenexus.org. It a) aggregates variant information from a large number of sources that are relevant to cancer research and clinical applications; b) allows high-performance programmatic access to the aggregated data via a unified API; c) provides a search interface and a reference page for individual cancer variants; d) provides user-friendly tools for annotating variants in patients; e) is freely available under an open source license and can be installed in a private cloud or local environment. Genome Nexus contains annotations from more than a dozen resources, including those that provide variant effect information (VEP), protein sequence annotation (Uniprot, Pfam, dbPTM), functional consequence prediction (Polyphen-2, Mutation Assessor, SIFT), population prevalence (gnomAD, dbSNP, ExAC), cancer population prevalence (Cancer Hotspots, SignalDB) and clinical actionability (OncoKB, CIViC, Clinvar). The annotations can be accessed through the website, the API, and a command line client. Genome Nexus is unique in providing a user friendly interface specific to cancer that allows high performance annotation of any variant. It is the main annotation service for the popular cancer genomics tool cBioPortal, which serves thousands of users daily. It is also offered as a standalone tool for annotation, allowing researchers and clinicians as well as genomic infrastructure developers to leverage it directly in their own workflows. For example, a local installation of Genome Nexus is used for annotating all variants in AACR Project GENIE. Citation Format: Ino de Bruijn, Xiang Li, Onur Sumer, Benjamin Gross, Robert Sheridan, Angelica Ochoa, Manda Wilson, Avery Wang, Hongxin Zhang, Aaron Lisman, Adam Abeshouse, Sander Rodenburg, Sjoerd van Hagen, Remond Fijneman, Gerrit Meijer, Nikolaus Schultz, Jianjiong Gao. Genome Nexus: A comprehensive resource for the annotation and interpretation of genomic variants in cancer [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 1156.