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Nucleic Acids Res. 2016 Jul 27;44(13):6274-86. doi: 10.1093/nar/gkw491. Epub 2016 Jun 3.

Copy number analysis of whole-genome data using BIC-seq2 and its application to detection of cancer susceptibility variants.

Author information

1
School of Mathematical Sciences and Center for Statistical Science, Peking University, Beijing 100871, China ruibinxi@math.pku.edu.cn.
2
Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
3
School of Mathematical Sciences and Center for Statistical Science, Peking University, Beijing 100871, China Center for Quantitative Biology, Peking University, Beijing 100871, China.
4
Department of Medical Informatics, College of Medicine, The Catholic University of Korea, 137-701 Seoul, Korea.
5
Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA peter_park@harvard.edu.

Abstract

Whole-genome sequencing data allow detection of copy number variation (CNV) at high resolution. However, estimation based on read coverage along the genome suffers from bias due to GC content and other factors. Here, we develop an algorithm called BIC-seq2 that combines normalization of the data at the nucleotide level and Bayesian information criterion-based segmentation to detect both somatic and germline CNVs accurately. Analysis of simulation data showed that this method outperforms existing methods. We apply this algorithm to low coverage whole-genome sequencing data from peripheral blood of nearly a thousand patients across eleven cancer types in The Cancer Genome Atlas (TCGA) to identify cancer-predisposing CNV regions. We confirm known regions and discover new ones including those covering KMT2C, GOLPH3, ERBB2 and PLAG1 Analysis of colorectal cancer genomes in particular reveals novel recurrent CNVs including deletions at two chromatin-remodeling genes RERE and NPM2 This method will be useful to many researchers interested in profiling CNVs from whole-genome sequencing data.

PMID:
27260798
PMCID:
PMC5772337
DOI:
10.1093/nar/gkw491
[Indexed for MEDLINE]
Free PMC Article

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