Important biological information uncovered in previously unaligned reads from chromatin immunoprecipitation experiments (ChIP-Seq)

Scientific Reports
Wilberforce Zachary OumaErich Grotewold

Abstract

Establishing the architecture of gene regulatory networks (GRNs) relies on chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) methods that provide genome-wide transcription factor binding sites (TFBSs). ChIP-Seq furnishes millions of short reads that, after alignment, describe the genome-wide binding sites of a particular TF. However, in all organisms investigated an average of 40% of reads fail to align to the corresponding genome, with some datasets having as much as 80% of reads failing to align. We describe here the provenance of previously unaligned reads in ChIP-Seq experiments from animals and plants. We show that a substantial portion corresponds to sequences of bacterial and metazoan origin, irrespective of the ChIP-Seq chromatin source. Unforeseen was the finding that 30%-40% of unaligned reads were actually alignable. To validate these observations, we investigated the characteristics of the previously unaligned reads corresponding to TAL1, a human TF involved in lineage specification of hemopoietic cells. We show that, while unmapped ChIP-Seq read datasets contain foreign DNA sequences, additional TFBSs can be identified from the previously unaligned ChIP-Seq reads. Our results indica...Continue Reading

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Citations

Apr 20, 2019·BMC Bioinformatics·Mara SangiovanniMario Rosario Guarracino

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Datasets Mentioned

BETA
SRR070251
SRR070252
SRR039100
SRR017605
SRX029597
GSM614003

Methods Mentioned

BETA
immunoprecipitation
ChIP-Seq
ChIP
PCR

Software Mentioned

BLAST
UCLUST
Bowtie
Stampy
FASTX
Illumina Genome Analyzer
MEME
Bio4j
MACS
Bowtie2

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