Title | ||
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Perm-seq: Mapping Protein-DNA Interactions in Segmental Duplication and Highly Repetitive Regions of Genomes with Prior-Enhanced Read Mapping. |
Abstract | ||
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Segmental duplications and other highly repetitive regions of genomes contribute significantly to cells' regulatory programs. Advancements in next generation sequencing enabled genome-wide profiling of protein-DNA interactions by chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq). However, interactions in highly repetitive regions of genomes have proven difficult to map since short reads of 50-100 base pairs (bps) from these regions map to multiple locations in reference genomes. Standard analytical methods discard such multi-mapping reads and the few that can accommodate them are prone to large false positive and negative rates. We developed Perm-seq, a prior-enhanced read allocation method for ChIP-seq experiments, that can allocate multi-mapping reads in highly repetitive regions of the genomes with high accuracy. We comprehensively evaluated Perm-seq, and found that our prior-enhanced approach significantly improves multi-read allocation accuracy over approaches that do not utilize additional data types. The statistical formalism underlying our approach facilitates supervising of multi-read allocation with a variety of data sources including histone ChIP-seq. We applied Perm-seq to 64 ENCODE ChIP-seq datasets from GM12878 and K562 cells and identified many novel protein-DNA interactions in segmental duplication regions. Our analysis reveals that although the protein-DNA interactions sites are evolutionarily less conserved in repetitive regions, they share the overall sequence characteristics of the protein-DNA interactions in non-repetitive regions. |
Year | DOI | Venue |
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2015 | 10.1371/journal.pcbi.1004491 | PLOS COMPUTATIONAL BIOLOGY |
DocType | Volume | Issue |
Journal | 11 | 10 |
ISSN | Citations | PageRank |
1553-7358 | 1 | 0.35 |
References | Authors | |
12 | 7 |
Name | Order | Citations | PageRank |
---|---|---|---|
Xin Zeng | 1 | 1 | 0.69 |
Bo Li | 2 | 578 | 45.93 |
Rene Welch | 3 | 1 | 0.35 |
Constanza Rojo | 4 | 1 | 0.35 |
Ye Zheng | 5 | 1 | 0.35 |
Colin N. Dewey | 6 | 386 | 24.24 |
Sündüz Keleş | 7 | 86 | 19.79 |