CONDEL: Detecting Copy Number Variation and Genotyping Deletion Zygosity from Single Tumor Samples Using Sequence Data

Abstract

Characterizing copy number variations (CNVs) from sequenced genomes is a both feasible and cost-effective way to search for driver genes in cancer diagnosis. A number of existing algorithms for CNV detection only explored part of the features underlying sequence data and copy number structures, resulting in limited performance. Here, we describe CONDEL, a method for detecting CNVs from single tumor samples using high-throughput sequence data. CONDEL utilizes a novel statistic in combination with a peel-off scheme to assess the statistical significance of genome bins, and adopts a Bayesian approach to infer copy number gains, losses, and deletion zygosity based on statistical mixture models. We compare CONDEL to six peer methods on a large number of simulation datasets, showing improved performance in terms of true positive and false positive rates, and further validate CONDEL on three real datasets derived from the 1000 Genomes Project and the EGA archive. CONDEL obtained higher consistent results in comparison with other three single sample-based methods, and exclusively identified a number of CNVs that were previously associated with cancers. We conclude that CONDEL is a powerful tool for detecting copy number variations on single tumor samples even if these are sequenced at low-coverage.