DeepSSV: detecting somatic small variants in paired tumor and normal sequencing data with convolutional neural network

Motivation: It is of considerable interest to detect somatic mutations in paired tumor and normal sequencing data. A number of callers that are based on statistical or machine learning approaches have been developed to detect somatic small variants. However, they take into consideration only limited information about the reference and potential variant allele in both samples at a candidate somatic site. Also, they differ in how biological and technological noises are addressed. Hence, they are expected to produce divergent outputs. Results: To overcome the drawbacks of existing somatic callers, we develop a deep learning-based tool called DeepSSV, which employs a convolutional neural network (CNN) model to learn increasingly abstract feature representations from the raw data in higher feature layers. DeepSSV creates a spatially-oriented representation of read alignments around the candidate somatic sites adapted for the convolutional architecture, which enables it to expand to effectively gather scattered evidences. Moreover, DeepSSV incorporates the mapping information of both reference-allele-supporting and variant-allele-supporting reads in the tumor and normal samples at a genomic site that are readily available in the pileup format file. Together, the CNN model can process the whole alignment information. Such representational richness allows the model to capture the dependencies in the sequence and identify context-based sequencing artifacts, and alleviates the need of post-call filters that heavily depend on prior knowledge. We fitted the model on ground truth somatic mutations, and did benchmarking experiments on simulated and real tumors. The benchmarking results demonstrate that DeepSSV outperforms its state-of-the-art competitors in overall F1 score.