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CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps

View ORCID ProfileTom Aharon Hait, View ORCID ProfileRan Elkon, View ORCID ProfileRon Shamir
doi: https://doi.org/10.1101/707158
Tom Aharon Hait
1The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
2Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Ran Elkon
2Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
3Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
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Ron Shamir
1The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
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  • For correspondence: rshamir@tau.ac.il
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Abstract

Spatiotemporal gene expression patterns are governed to a large extent by enhancer elements, typically located distally from their target genes. Identification of enhancer-promoter (EP) links that are specific and functional in individual cell types is a key challenge in understanding gene regulation. We introduce CT-FOCS, a new statistical inference method that utilizes multiple replicates per cell type to infer cell type-specific EP links. Computationally predicted EP links are usually benchmarked against experimentally determined chromatin interactions measured by ChIA-PET and promoter-capture HiC techniques. We expand this validation scheme by using also loops that overlap in their anchor sites. In analyzing 1,366 samples from ENCODE, Roadmap epigenomics and FANTOM5, CT-FOCS inferred highly cell type-specific EP links more accurately than state-of-the-art methods. We illustrate how our inferred EP links drive cell type-specific gene expression and regulation.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • http://acgt.cs.tau.ac.il/ct-focs/

  • List of abbreviations

    EP
    Enhancer-Promoter
    CAGE
    Cap Analysis of Gene Expression
    CLS
    connected loop set
    ct-link
    Cell-Type specific enhancer-promoter link
    DHS
    DNase-I Hypersensitive Site
    TF
    transcription factor
  • Copyright 
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    Posted May 10, 2020.
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    CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps
    Tom Aharon Hait, Ran Elkon, Ron Shamir
    bioRxiv 707158; doi: https://doi.org/10.1101/707158
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    CT-FOCS: a novel method for inferring cell type-specific enhancer-promoter maps
    Tom Aharon Hait, Ran Elkon, Ron Shamir
    bioRxiv 707158; doi: https://doi.org/10.1101/707158

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