Var|Decrypt: a novel and user-friendly tool to explore and prioritize variants in whole-exome sequencing data

Abstract

AbstractMotivationHigh throughput sequencing (HTS) offers unprecedented opportunities for the discovery of causative gene variants in multiple human disorders including cancers, and has revolutionized clinical diagnostics. However, despite more than a decade of use of HTS-based assays, extracting relevant functional information from whole exome sequencing (WES) data remains challenging, especially for non-specialists lacking in-depth bioinformatic skills.ResultsTo address this limitation, we developed Var|Decrypt, a web-based tool designed to greatly facilitate WES data browsing and analysis. Var|Decrypt offers a wide range of gene and variant filtering possibilities, clustering and enrichment tools, providing an efficient way to derive patient-specific functional information and to prioritize gene variants for functional analyses. We applied Var|Decrypt on WES datasets of 10 acute erythroid leukemia patients, a rare and aggressive form of leukemia, and recovered known disease oncogenes in addition to novel putative drivers. We additionally benchmarked Var|Decrypt on an independent dataset of ~90 multiple myeloma WES, recapitulating the identified deregulated genes and pathways, showing the general applicability and versatility of Var|Decrypt for WES analysis.