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BMC Bioinformatics

, 16:349

Results and data

Abstract

BackgroundChIP-seq experiments are widely used to detect and study DNA-protein interactions, such as transcription factor binding and chromatin modifications. However, downstream analysis of ChIP-seq data is currently restricted to the evaluation of signal intensity and the detection of enriched regions peaks in the genome. Other features of peak shape are almost always neglected, despite the remarkable differences shown by ChIP-seq for different proteins, as well as by distinct regions in a single experiment.

ResultsWe hypothesize that statistically significant differences in peak shape might have a functional role and a biological meaning. Thus, we design five indices able to summarize peak shapes and we employ multivariate clustering techniques to divide peaks into groups according to both their complexity and the intensity of their coverage function. In addition, our novel analysis pipeline employs a range of statistical and bioinformatics techniques to relate the obtained peak shapes to several independent genomic datasets, including other genome-wide protein-DNA maps and gene expression experiments. To clarify the meaning of peak shape, we apply our methodology to the study of the erythroid transcription factor GATA-1 in K562 cell line and in megakaryocytes.

ConclusionsOur study demonstrates that ChIP-seq profiles include information regarding the binding of other proteins beside the one used for precipitation. In particular, peak shape provides new insights into cooperative transcriptional regulation and is correlated to gene expression.

KeywordsChIP-seq Transcription regulation GATA-1 Peak shape AbbreviationsChIP-exoChromatin ImmunoPrecipitation exonuclease

ChIP-seqChromatin ImmunoPrecipitation sequencing

DNase-seqDNase I hypersensitive sites sequencing

GOGene Ontology

RNA-seqRNA sequencing

RPKMReads Per Kilobase per Million

TFTranscription Factor

Electronic supplementary materialThe online version of this article doi:10.1186-s12859-015-0787-6 contains supplementary material, which is available to authorized users.

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Author: Marzia A. Cremona - Laura M. Sangalli - Simone Vantini - Gaetano I. Dellino - Pier Giuseppe Pelicci - Piercesare Secchi

Source: https://link.springer.com/



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