Ephesus: A curation workflow tool for the clinical interpretation of genomic variants.

Abstract

e14074 Background: Accurate and comprehensive interpretation of genomic variants has become a bottleneck in clinical sequencing applications due to the accelerated implementation of precision oncology and the rapid growth of relevant biomedical findings. We therefore are motivated to build Ephesus, a framework enabling curation of clinical evidence for biomarkers in somatic cancers. Currently Ephesus is the primary content source for Roche NAVIFY Mutation Profiler (NMP). Methods: Ephesus’ data model ensures adherence to best practice in clinical genomic content curation. Variant classification followed the AMP guidelines for somatic variant interpretation. Approvals and recommendations from regulatory agencies and organizations (FDA, NCCN, etc.) are applied on a regional basis. The data model is mapped to a set of PostgreSQL relational tables. Strategies such as data normalization according to standard ontologies, a submit-review-approval workflow with change logs, and biologically relevant datatype constraints are adopted to enforce data integrity. Ephesus is deployed as a web application, of which the UI allows users to conduct edits, filtering, sorting and bulk operations on entities by attributes. To maximize curation efficiency, a number of inference rules are applied before the content is ingested into NMP. Results: Currently Ephesus is developed to guide data collection, browsing and summarizing related to these primary entities: Biomarkers, Evidence items, Genes, Variants, Variant groups, and Drugs. The content exported on 2020/01/27 contains > 170K biomarker profiles (including combinations), in the context of 13 major cancer types. To evaluate the clinical reporting value of the curated knowledge, more than 60k real clinical cancer patient samples from the AACR GENIE project were queried against Ephesus. We compared the results to the latest content from several major knowledgebases. We see that the performance of Ephesus/NMP excels the others. Conclusions: We have developed Ephesus, a practical content curation framework which provides a highly structured and user-friendly environment for clinically relevant somatic biomarkers. The framework improved the productivity and quality of the manual curation, met clinical interpretation scope and complexity, and assures data integrity and auditability. [Table: see text]