ExCNVSS: A Noise-Robust Method for Copy Number Variation Detection in Whole Exome Sequencing Data

Copy number variations (CNVs) are structural variants associated with human diseases. Recent studies verified that disease-related genes are based on the extraction of rare de novo and transmitted CNVs from exome sequencing data. The need for more efficient and accurate methods has increased, which still remains a challenging problem due to coverage biases, as well as the sparse, small-sized, and noncontinuous nature of exome sequencing. In this study, we developed a new CNV detection method, ExCNVSS, based on read coverage depth evaluation and scale-space filtering to resolve these problems. We also developed the method ExCNVSS_noRatio, which is a version of ExCNVSS, for applying to cases with an input of test data only without the need to consider the availability of a matched control. To evaluate the performance of our method, we tested it with 11 different simulated data sets and 10 real HapMap samples’ data. The results demonstrated that ExCNVSS outperformed three other state-of-the-art methods and that our method corrected for coverage biases and detected all-sized CNVs even without matched control data.