title: CNV-guided multi-read allocation for ChIP-seq.
abstract: BACKGROUND
  In chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and other short-read sequencing experiments, a considerable fraction of the short reads align to multiple locations on the reference genome (multi-reads). Inferring the origin of multi-reads is critical for accurately mapping reads to repetitive regions. Current state-of-the-art multi-read allocation algorithms rely on the read counts in the local neighborhood of the alignment locations and ignore the variation in the copy numbers of these regions. Copy-number variation (CNV) can directly affect the read densities and, therefore, bias allocation of multi-reads.
  
  
  RESULTS
  We propose cnvCSEM (CNV-guided ChIP-Seq by expectation-maximization algorithm), a flexible framework that incorporates CNV in multi-read allocation. cnvCSEM eliminates the CNV bias in multi-read allocation by initializing the read allocation algorithm with CNV-aware initial values. Our data-driven simulations illustrate that cnvCSEM leads to higher read coverage with satisfactory accuracy and lower loss in read-depth recovery (estimation). We evaluate the biological relevance of the cnvCSEM-allocated reads and the resultant peaks with the analysis of several ENCODE ChIP-seq datasets.
  
  
  METHODS
  Available at http://www.stat.wisc.edu/∼qizhang/
  
  
  BACKGROUND
  : qizhang@stat.wisc.edu or keles@stat.wisc.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Department of Biostatistics and Medical Informatics, 425 Henry Mall and Department of Statistics, 1300 University Avenue, Madison, WI 53706, USA.
authors: Qi
authors: Q
authors: Zhang
authors: Department of Biostatistics and Medical Informatics, 425 Henry Mall and Department of Statistics, 1300 University Avenue, Madison, WI 53706, USA Department of Biostatistics and Medical Informatics, 425 Henry Mall and Department of Statistics, 1300 University Avenue, Madison, WI 53706, USA.
authors: Sündüz
authors: S
authors: Keleş
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D056915:DNA Copy Number Variations; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors