ChIP-PaM: an algorithm to identify protein-DNA interaction using ChIP-Seq data.
BACKGROUND
ChIP-Seq is a powerful tool for identifying the interaction between genomic regulators and their bound DNAs, especially for locating transcription factor binding sites. However, high cost and high rate of false discovery of transcription factor binding sites identified from ChIP-Seq data significantly limit its application.


RESULTS
Here we report a new algorithm, ChIP-PaM, for identifying transcription factor target regions in ChIP-Seq datasets. This algorithm makes full use of a protein-DNA binding pattern by capitalizing on three lines of evidence: 1) the tag count modelling at the peak position, 2) pattern matching of a specific tag count distribution, and 3) motif searching along the genome. A novel data-based two-step eFDR procedure is proposed to integrate the three lines of evidence to determine significantly enriched regions. Our algorithm requires no technical controls and efficiently discriminates falsely enriched regions from regions enriched by true transcription factor (TF) binding on the basis of ChIP-Seq data only. An analysis of real genomic data is presented to demonstrate our method.


CONCLUSIONS
In a comparison with other existing methods, we found that our algorithm provides more accurate binding site discovery while maintaining comparable statistical power.
Department of Biostatistics, St, Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. song.wu@stjude.org
Song
S
Wu
Jianmin
J
Wang
Wei
W
Zhao
Stanley
S
Pounds
Cheng
C
Cheng
D000465:Algorithms; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D014157:Transcription Factors; D004247:DNA