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Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach.

Publication ,  Journal Article
Edsall, LE; Berrio, A; Majoros, WH; Swain-Lenz, D; Morrow, S; Shibata, Y; Safi, A; Wray, GA; Crawford, GE; Allen, AS
Published in: Genome Biol Evol
October 1, 2019

Changes in transcriptional regulation are thought to be a major contributor to the evolution of phenotypic traits, but the contribution of changes in chromatin accessibility to the evolution of gene expression remains almost entirely unknown. To address this important gap in knowledge, we developed a new method to identify DNase I Hypersensitive (DHS) sites with differential chromatin accessibility between species using a joint modeling approach. Our method overcomes several limitations inherent to conventional threshold-based pairwise comparisons that become increasingly apparent as the number of species analyzed rises. Our approach employs a single quantitative test which is more sensitive than existing pairwise methods. To illustrate, we applied our joint approach to DHS sites in fibroblast cells from five primates (human, chimpanzee, gorilla, orangutan, and rhesus macaque). We identified 89,744 DHS sites, of which 41% are identified as differential between species using the joint model compared with 33% using the conventional pairwise approach. The joint model provides a principled approach to distinguishing single from multiple chromatin accessibility changes among species. We found that nondifferential DHS sites are enriched for nucleotide conservation. Differential DHS sites with decreased chromatin accessibility relative to rhesus macaque occur more commonly near transcription start sites (TSS), while those with increased chromatin accessibility occur more commonly distal to TSS. Further, differential DHS sites near TSS are less cell type-specific than more distal regulatory elements. Taken together, these results point to distinct classes of DHS sites, each with distinct characteristics of selection, genomic location, and cell type specificity.

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Published In

Genome Biol Evol

DOI

EISSN

1759-6653

Publication Date

October 1, 2019

Volume

11

Issue

10

Start / End Page

3035 / 3053

Location

England

Related Subject Headings

  • Transcription Initiation Site
  • Pongo
  • Pan troglodytes
  • Models, Genetic
  • Macaca mulatta
  • Humans
  • Gorilla gorilla
  • Genomics
  • Evolution, Molecular
  • Developmental Biology
 

Citation

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Edsall, L. E., Berrio, A., Majoros, W. H., Swain-Lenz, D., Morrow, S., Shibata, Y., … Allen, A. S. (2019). Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach. Genome Biol Evol, 11(10), 3035–3053. https://doi.org/10.1093/gbe/evz218
Edsall, Lee E., Alejandro Berrio, William H. Majoros, Devjanee Swain-Lenz, Shauna Morrow, Yoichiro Shibata, Alexias Safi, Gregory A. Wray, Gregory E. Crawford, and Andrew S. Allen. “Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach.Genome Biol Evol 11, no. 10 (October 1, 2019): 3035–53. https://doi.org/10.1093/gbe/evz218.
Edsall LE, Berrio A, Majoros WH, Swain-Lenz D, Morrow S, Shibata Y, et al. Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach. Genome Biol Evol. 2019 Oct 1;11(10):3035–53.
Edsall, Lee E., et al. “Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach.Genome Biol Evol, vol. 11, no. 10, Oct. 2019, pp. 3035–53. Pubmed, doi:10.1093/gbe/evz218.
Edsall LE, Berrio A, Majoros WH, Swain-Lenz D, Morrow S, Shibata Y, Safi A, Wray GA, Crawford GE, Allen AS. Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach. Genome Biol Evol. 2019 Oct 1;11(10):3035–3053.
Journal cover image

Published In

Genome Biol Evol

DOI

EISSN

1759-6653

Publication Date

October 1, 2019

Volume

11

Issue

10

Start / End Page

3035 / 3053

Location

England

Related Subject Headings

  • Transcription Initiation Site
  • Pongo
  • Pan troglodytes
  • Models, Genetic
  • Macaca mulatta
  • Humans
  • Gorilla gorilla
  • Genomics
  • Evolution, Molecular
  • Developmental Biology