Purpose: Interpretation of genomic variants in tumor samples still presents a challenge in research and the clinical setting. A major issue is that information for variant interpretation is fragmented across disparate databases, and aggregation of information from these requires building 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 that are relevant to cancer research and clinical applications, (2) allows high-performance programmatic access to the aggregated data via a unified application programming interface, (3) provides a reference page for individual cancer variants, (4) provides user-friendly tools for annotating variants in patients, and (5) is freely available under an open source license and can be installed in a private cloud or 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 variant effect information (variant effect predictor), protein sequence annotation (Uniprot, Pfam, and dbPTM), functional consequence prediction (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 to clinicians, researchers, and bioinformaticians. We cover single-variant annotation, cohort analysis, and programmatic use of the application programming interface. Genome Nexus is unique in providing a user-friendly interface specific to cancer that allows high-performance annotation of any variant including unknown ones.
Conclusion: Interpretation of cancer genomic variants is improved tremendously by having an integrated resource for annotations. Genome Nexus is freely available under an open source license.