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

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 indicate that the re-evaluation of previously unaligned reads from ChIP-Seq experiments will significantly contribute to TF target identification and determination of emerging properties of GRNs.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ouma WZ,Mejia-Guerra MK,Yilmaz A,Pareja-Tobes P,Li W,Doseff AI,Grotewold E

doi

10.1038/srep08635

subject

Has Abstract

pub_date

2015-03-02 00:00:00

pages

8635

issn

2045-2322

pii

srep08635

journal_volume

5

pub_type

杂志文章

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