Pinpointing transcription factor binding sites from ChIP-seq data with SeqSite.
BACKGROUND
Chromatin immunoprecipitation combined with the next-generation DNA sequencing technologies (ChIP-seq) becomes a key approach for detecting genome-wide sets of genomic sites bound by proteins, such as transcription factors (TFs). Several methods and open-source tools have been developed to analyze ChIP-seq data. However, most of them are designed for detecting TF binding regions instead of accurately locating transcription factor binding sites (TFBSs). It is still challenging to pinpoint TFBSs directly from ChIP-seq data, especially in regions with closely spaced binding events.


RESULTS
With the aim to pinpoint TFBSs at a high resolution, we propose a novel method named SeqSite, implementing a two-step strategy: detecting tag-enriched regions first and pinpointing binding sites in the detected regions. The second step is done by modeling the tag density profile, locating TFBSs on each strand with a least-squares model fitting strategy, and merging the detections from the two strands. Experiments on simulation data show that SeqSite can locate most of the binding sites more than 40-bp from each other. Applications on three human TF ChIP-seq datasets demonstrate the advantage of SeqSite for its higher resolution in pinpointing binding sites compared with existing methods.


CONCLUSIONS
We have developed a computational tool named SeqSite, which can pinpoint both closely spaced and isolated binding sites, and consequently improves the resolution of TFBS detection from ChIP-seq data.
MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST / Department of Automation, Tsinghua University, Beijing 100084, China.
Xi
X
Wang
Xuegong
X
Zhang
D001665:Binding Sites; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D016000:Cluster Analysis; D019295:Computational Biology; D030541:Databases, Genetic; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000099229:RE1-Silencing Transcription Factor
D051268:GA-Binding Protein Transcription Factor; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D000099229:RE1-Silencing Transcription Factor; C494079:STAT1 protein, human