svBreak: A New Approach for the Detection of Structural Variant Breakpoints Based on Convolutional Neural Network

Abstract

Structural variation (SV) is an important type of genome variation and confers susceptibility to human cancer diseases. Systematic analysis of SVs has become a crucial step for the exploration of mechanisms and precision diagnosis of cancers. The central point is how to accurately detect SV breakpoints by using next-generation sequencing (NGS) data. Due to the cooccurrence of multiple types of SVs in the human genome and the intrinsic complexity of SVs, the discrimination of SV breakpoint types is a challenging task. In this paper, we propose a convolutional neural network- (CNN-) based approach, called svBreak, for the detection and discrimination of common types of SV breakpoints. The principle of svBreak is that it extracts a set of SV-related features for each genome site from the sequencing reads aligned to the reference genome and establishes a data matrix where each row represents one site and each column represents one feature and then adopts a CNN model to analyze such data matrix for the prediction of SV breakpoints. The performance of the proposed approach is tested via simulation studies and application to a real sequencing sample. The experimental results demonstrate the merits of the proposed approach when compared with existing methods. Thus, svBreak can be expected to be a supplementary approach in the field of SV analysis in human tumor genomes.