Name
Title | ||
|---|---|---|
Discovering Transcription Factor Binding Sites In Highly Repetitive Regions Of Genomes With Multi-Read Analysis Of Chip-Seq Data |
Abstract | ||
|---|---|---|
Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is rapidly replacing chromatin immunoprecipitation combined with genome-wide tiling array analysis (ChIP-chip) as the preferred approach for mapping transcription-factor binding sites and chromatin modifications. The state of the art for analyzing ChIP-seq data relies on using only reads that map uniquely to a relevant reference genome (uni-reads). This can lead to the omission of up to 30% of alignable reads. We describe a general approach for utilizing reads that map to multiple locations on the reference genome (multi-reads). Our approach is based on allocating multi-reads as fractional counts using a weighted alignment scheme. Using human STAT1 and mouse GATA1 ChIP-seq datasets, we illustrate that incorporation of multi-reads significantly increases sequencing depths, leads to detection of novel peaks that are not otherwise identifiable with unireads, and improves detection of peaks in mappable regions. We investigate various genome-wide characteristics of peaks detected only by utilization of multi-reads via computational experiments. Overall, peaks from multi-read analysis have similar characteristics to peaks that are identified by uni-reads except that the majority of them reside in segmental duplications. We further validate a number of GATA1 multi-read only peaks by independent quantitative real-time ChIP analysis and identify novel target genes of GATA1. These computational and experimental results establish that multi-reads can be of critical importance for studying transcription factor binding in highly repetitive regions of genomes with ChIP-seq experiments. |
Year | DOI | Venue |
|---|---|---|
2011 | 10.1371/journal.pcbi.1002111 | PLOS COMPUTATIONAL BIOLOGY |
Keywords | Field | DocType |
transcription factors,genomics,chromatin immunoprecipitation,genome,binding sites,real time,transcription factor binding site,chip,computer experiment,high throughput | Genome,DNA binding site,Tiling array,ChIP-sequencing,Biology,Genomics,Bioinformatics,Chromatin immunoprecipitation,Genetics,Reference genome,Segmental duplication | Journal |
Volume | Issue | ISSN |
7 | 7 | 1553-7358 |
Citations | PageRank | References |
16 | 1.15 | 15 |
Authors | ||
8 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Dongjun Chung | 1 | 19 | 1.56 |
| Pei Fen Kuan | 2 | 24 | 3.71 |
| Bo Li | 3 | 578 | 45.93 |
| Rajendran Sanalkumar | 4 | 16 | 1.15 |
| Kun Liang | 5 | 16 | 1.15 |
| Emery H Bresnick | 6 | 16 | 1.15 |
| Colin N. Dewey | 7 | 386 | 24.24 |
| Sündüz Keleş | 8 | 17 | 1.52 |