Rapid and powerful detection of subtle allelic imbalance from exome sequencing data with hapLOHseq.
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.
Department of Translational Molecular Pathology The Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
F Anthony
FA
San Lucas
Department of Translational Molecular Pathology Department of Epidemiology.
Smruthy
S
Sivakumar
Department of Translational Molecular Pathology Department of Epidemiology.
Selina
S
Vattathil
Department of Epidemiology.
Jerry
J
Fowler
Department of Translational Molecular Pathology Department of Gastrointestinal Medical Oncology Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Eduardo
E
Vilar
The Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA Department of Epidemiology.
Paul
P
Scheet
D022981:Allelic Imbalance; D059472:Exome; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D012984:Software