Onkopus: precise interpretation and prioritization of sequence variants for biomedical research and precision medicine

One of the major challenges in precision oncology is the identification of pathogenic, actionable variants and the selection of personalized treatments. We present Onkopus, a variant interpretation framework based on a modular architecture, for interpreting and prioritizing genetic alterations in cancer patients. A multitude of tools and databases are integrated into Onkopus to provide a comprehensive overview about the consequences of a variant, each with its own semantic, including pathogenicity predictions, allele frequency, biochemical and protein features, and therapeutic options. We present the characteristics of variants and personalized therapies in a clear and concise form, supported by interactive plots. To support the interpretation of variants of unknown significance (VUS), we present a protein analysis based on protein structures, which allows variants to be analyzed within the context of the entire protein, thereby serving as a starting point for understanding the underlying causes of variant pathogenicity. Onkopus has the potential to significantly enhance variant interpretation and the selection of actionable variants for identifying new targets, drug screens, drug testing using organoids, or personalized treatments in molecular tumor boards. We provide a free public instance of Onkopus at https://mtb.bioinf.med.uni-goettingen.de/onkopus.