Rapid and powerful detection of subtle allelic imbalance from exome sequencing data with hapLOHseq.

Abstract

The detection of subtle genomic allelic imbalance events has many potential applications. For example, identifying cancer-associated allelic imbalanced regions in low tumor-cellularity samples or in low-proportion tumor subclones can be used for early cancer detection, prognostic assessment and therapeutic selection in cancer patients. We developed hapLOHseq for the detection of subtle allelic imbalance events from next-generation sequencing data. Our method identified events of 10 megabases or greater occurring in as little as 16% of the sample in exome sequencing data (at 80×) and 4% in whole genome sequencing data (at 30×), far exceeding the capabilities of existing software. We also found hapLOHseq to be superior at detecting large chromosomal changes across a series of pancreatic samples from TCGA. hapLOHseq is available at scheet.org/software, distributed under an open source MIT license. pscheet@alum.wustl.edu Supplementary data are available at Bioinformatics online.