Accurate somatic variant detection using weakly supervised deep learning

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.

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