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

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


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.

MeSH terms

  • Algorithms
  • Base Composition / genetics
  • Bayes Theorem
  • Carrier Proteins / genetics
  • Chromatin Assembly and Disassembly / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Copy Number Variations / genetics*
  • DNA-Binding Proteins / genetics
  • Genome, Human*
  • Humans
  • Membrane Proteins / genetics
  • Neoplasm Proteins / genetics
  • Nucleoplasmins / genetics
  • Receptor, ErbB-2 / genetics
  • Sequence Analysis, DNA / methods*


  • Carrier Proteins
  • DNA-Binding Proteins
  • GOLPH3 protein, human
  • KMT2D protein, human
  • Membrane Proteins
  • NPM2 protein, human
  • Neoplasm Proteins
  • Nucleoplasmins
  • PLAG1 protein, human
  • RERE protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2