Optimization of Signal Decomposition Matched Filtering (SDMF) for Improved Detection of Copy-Number Variations

摘要

We aim to improve the performance of the previously proposed signal decomposition matched filtering (SDMF) method [26] for the detection of copy-number variations (CNV) in the human genome. Through simulations, we show that the modified SDMF is robust even at high noise levels and outperforms the original SDMF method, which indirectly depends on CNV frequency. Simulations are also used to develop a systematic approach for selecting relevant parameter thresholds in order to optimize sensitivity, specificity and computational efficiency. We apply the modified method to array CGH data from normal samples in the cancer genome atlas (TCGA) and compare detected CNVs to those estimated using circular binary segmentation (CBS) [19] , a hidden Markov model (HMM)-based approach [11] and a subset of CNVs in the Database of Genomic Variants. We show that a substantial number of previously identified CNVs are detected by the optimized SDMF, which also outperforms the other two methods.