Accurate somatic variant detection using weakly supervised deep learning.

Krishnamachari, Kiran; Lu, Dylan; Swift-Scott, Alexander; Yeraliyev, Anuar; Lee, Kayla; Huang, Weitai; Leng, Sim Ngak; Skanderup, Anders Jacobsen · Nat Commun · 2022

basic_science · Level V

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Abstract

Identification of somatic mutations in tumor samples is commonly based on statistical methods in combination with heuristic filters. Here we develop VarNet, an end-to-end deep learning approach for identification of somatic variants from aligned tumor and matched normal DNA reads. VarNet is trained using image representations of 4.6 million high-confidence somatic variants annotated in 356 tumor whole genomes. We benchmark VarNet across a range of publicly available datasets, demonstrating performance often exceeding current state-of-the-art methods. Overall, our results demonstrate how a scalable deep learning approach could augment and potentially supplant human engineered features and heuristic filters in somatic variant calling.

Medical subject headings