High-throughput DNA sequencing enables detection of copy number variations (CNVs) on the genome-wide scale with finer resolution compared to array-based methods, but suffers from biases and artifacts that lead to false discoveries and low sensitivity. We describe CODEX2, a statistical framework for full-spectrum CNV profiling that is sensitive for variants with both common and rare population frequencies and that is applicable to study designs with and without negative control samples. We

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... trate and evaluate CODEX2 on whole-exome and targeted sequencing data, where biases are the most prominent. CODEX2 outperforms existing methods and, in particular, significantly improves sensitivity for common CNVs.