This article was originally published here
JCO Clin Cancer Inform. Feb 2022;6:e2100144. doi: 10.1200/CCI.21.00144.
OBJECTIVE: The interpretation of genomic variants in tumor samples continues to present a challenge in research and clinical settings. A major problem is that information for variant interpretation is fragmented in disparate databases, and aggregating information from these requires building an extensive infrastructure. To this end, we have developed Genome Nexus, a one-stop-shop for variant annotation with a user-friendly interface for cancer researchers and clinicians.
METHODS: Genome Nexus (1) aggregates variant information from sources relevant to cancer research and clinical applications, (2) enables high-performance programmatic access to aggregated data through a unified application programming interface, (3) provides a reference page for individual cancer variants, (4) provides user-friendly tools to annotate variants in patients, and (5) is freely available under an open source license and can be installed in a private cloud or a local environment and integrated with local institutional resources.
RESULTS: Genome Nexus is available at https://www.genomenexus.org. It displays annotations from more than a dozen resources, including those that provide information on variant effects (variant effect predictor), protein sequence annotation (Uniprot, Pfam, and dbPTM), prediction of functional consequences (Polyphen-2, Mutation Assessor and SIFT), population prevalences (gnomAD, dbSNP and ExAC), cancer population prevalences (cancer hotspots and SignalDB) and clinical actionability (OncoKB, CIViC and ClinVar) . We describe several use cases that demonstrate the utility of Genome Nexus for clinicians, researchers, and bioinformaticians. We cover single-variant annotation, cohort analysis, and programmatic use of the application programming interface. Genome Nexus is unique in that it provides a user-friendly, cancer-specific interface that enables high-performance annotation of any variant, including unknowns.
CONCLUSION: The interpretation of cancer genomic variants is significantly improved by having an integrated resource for annotations. Genome Nexus is freely available under an open source license.