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Integrative analysis of epigenetics data identifies gene-specific regulatory elements

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posted on 2023-11-29, 18:06 authored by Florian Schmidt, Alexander Marx, Nina Baumgarten, Marie Hebel, Martin Wegner, Manuel Kaulich, Matthias S. Leisegang, Rals P. Brandes, Jonathan Göke, Jilles VreekenJilles Vreeken, Marcel H. Schulz
Understanding how epigenetic variation in non-coding regions is involved in distal gene-expression regulation is an important problem. Regulatory regions can be associated to genes using large-scale datasets of epigenetic and expression data. However, for regions of complex epigenomic signals and enhancers that regulate many genes, it is difficult to understand these associations. We present StitchIt, an approach to dissect epigenetic variation in a gene-specific manner for the detection of regulatory elements (REMs) without relying on peak calls in individual samples. StitchIt segments epigenetic signal tracks over many samples to generate the location and the target genes of a REM simultaneously. We show that this approach leads to a more accurate and refined REM detection compared to standard methods even on heterogeneous datasets, which are challenging to model. Also, StitchIt REMs are highly enriched in experimentally determined chromatin interactions and expression quantitative trait loci. We validated several newly predicted REMs using CRISPR-Cas9 experiments, thereby demonstrating the reliability of StitchIt. StitchIt is able to dissect regulation in superenhancers and predicts thousands of putative REMs that go unnoticed using peak-based approaches suggesting that a large part of the regulome might be uncharted water.

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Preferred Citation

Florian Schmidt, Alexander Marx, Nina Baumgarten, Marie Hebel, Martin Wegner, Manuel Kaulich, Matthias Leisegang, Rals Brandes, Jonathan Göke, Jilles Vreeken and Marcel Schulz. Integrative analysis of epigenetics data identifies gene-specific regulatory elements. In: Nucleic Acids Research. 2021.

Primary Research Area

  • Algorithmic Foundations and Cryptography

Legacy Posted Date

2021-12-20

Journal

Nucleic Acids Research

Open Access Type

  • Gold

Sub Type

  • Article

BibTeX

@article{cispa_all_3553, title = "Integrative analysis of epigenetics data identifies gene-specific regulatory elements", author = "Schmidt, Florian and Marx, Alexander and Baumgarten, Nina and Hebel, Marie and Wegner, Martin and Kaulich, Manuel and Leisegang, Matthias S. and Brandes, Rals P. and Göke, Jonathan and Vreeken, Jilles and Schulz, Marcel H.", journal="{Nucleic Acids Research}", year="2021", }

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