Integrating motif, DNA accessibility and gene expression data to build regulatory maps in an organism

Nucleic Acids Research
Charles BlattiSaurabh Sinha

Abstract

Characterization of cell type specific regulatory networks and elements is a major challenge in genomics, and emerging strategies frequently employ high-throughput genome-wide assays of transcription factor (TF) to DNA binding, histone modifications or chromatin state. However, these experiments remain too difficult/expensive for many laboratories to apply comprehensively to their system of interest. Here, we explore the potential of elucidating regulatory systems in varied cell types using computational techniques that rely on only data of gene expression, low-resolution chromatin accessibility, and TF-DNA binding specificities ('motifs'). We show that static computational motif scans overlaid with chromatin accessibility data reasonably approximate experimentally measured TF-DNA binding. We demonstrate that predicted binding profiles and expression patterns of hundreds of TFs are sufficient to identify major regulators of ∼200 spatiotemporal expression domains in the Drosophila embryo. We are then able to learn reliable statistical models of enhancer activity for over 70 expression domains and apply those models to annotate domain specific enhancers genome-wide. Throughout this work, we apply our motif and accessibility based...Continue Reading

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Citations

Jun 4, 2016·Nucleic Acids Research·Pei-Chen Peng, Saurabh Sinha
Apr 23, 2016·PLoS Computational Biology·Antonio L C Gomes, Harris H Wang
Dec 23, 2017·Molecular Biology and Evolution·Cristina M AlexandreChristin Queitsch
Aug 25, 2018·PLoS Computational Biology·Alena van BömmelMartin Vingron
Sep 27, 2018·PLoS Computational Biology·Farzaneh Khajouei, Saurabh Sinha
May 23, 2019·Genome Biology and Evolution·Pei-Chen PengSaurabh Sinha
Jun 20, 2020·Nature Communications·Sonia TarazonaAna Conesa
Jun 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Zhana DurenWing Hung Wong
Nov 19, 2015·Genome Research·Susan Q ShenJoseph C Corbo
Aug 17, 2021·Frontiers in Genetics·Yesid Cuesta-AstrozAlberto J M Martin
Sep 12, 2021·Nucleic Acids Research·Payam Dibaeinia, Saurabh Sinha

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Methods Mentioned

BETA
Hi-C
ChIP-chip
ChIP-seq
ChIP
1-hybrid
RNA-seq

Software Mentioned

Genome Surveyor
Genome browser
phastCons
BestReg
RFVO
MultiSpec
ModENCODE
Stubb
Acc
REDfly

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