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Precise interpretation and prioritization of sequence variants with Onkopus for supporting molecular tumor boards

Kurz, N. S.; Kornrumpf, K.; Tucholski, T.; Drofenik, K.; König, A.; Beissbarth, T.; Dönitz, J.

2024-09-25 oncology
10.1101/2024.09.24.24314298 medRxiv
Show abstract

One of the major challenges in precision medicine 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. We show that aggregation and harmonization of clinical databases, coupled with querying of these databases to varying associated biomarkers, can increase the number of identified therapeutic options. We present a protein analysis of mutated sites and show that protein characteristics can provide potential indicators for the functional impairment of variants of unknown significance. Variant interpretation systems like Onkopus have the potential to significantly enhance the performance of personalized treatments, as they reduce the time required for variant interpretation and manual evaluation of personalized treatments, while maintaining reproducibility and traceability. We provide a free public instance of Onkopus at https://mtb.bioinf.med.uni-goettingen.de/onkopus.

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