Robust enhancer-gene regulation identified by single-cell transcriptomes and epigenomes

Abstract: Single-cell sequencing could help to solve the fundamental challenge of linking millions of cell-type-specific enhancers with their target genes. However, this task is confounded by patterns of gene co-expression in much the same way that genetic correlation due to linkage disequilibrium confounds fine-mapping in genome-wide association studies (GWAS). We developed a non-parametric permutation-based procedure to establish stringent statistical criteria to control the risk of false-positive associations in enhancer-gene association studies (EGAS). We applied our procedure to large-scale transcriptome and epigenome data from multiple tissues and species, including the mouse and human brain, to predict enhancer-gene associations genome wide. We tested the functional validity of our predictions by comparing them with chromatin conformation data and causal enhancer perturbation experiments. Our study shows how controlling for gene co-expression enables robust enhancer-gene linkage using single-cell sequencing data

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Cell genomics. - 3, 7 (2023) , 100342, ISSN: 2666-979X

Klassifikation
Biowissenschaften, Biologie

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2023
Urheber
Xie, Fangming
Armand, Ethan J.
Yao, Zizhen
Liu, Hanqing
Bartlett, Anna
Behrens, M. Margarita
Li, Yang Eric
Lucero, Jacinta D.
Luo, Chongyuan
Nery, Joseph R.
Pinto-Duarte, Antonio
Poirion, Olivier B.
Preißl, Sebastian
Rivkin, Angeline C.
Tasic, Bosiljka
Zeng, Hongkui
Ren, Bing
Ecker, Joseph R.
Mukamel, Eran A.

DOI
10.1016/j.xgen.2023.100342
URN
urn:nbn:de:bsz:25-freidok-2381987
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:42 MEZ

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Beteiligte

  • Xie, Fangming
  • Armand, Ethan J.
  • Yao, Zizhen
  • Liu, Hanqing
  • Bartlett, Anna
  • Behrens, M. Margarita
  • Li, Yang Eric
  • Lucero, Jacinta D.
  • Luo, Chongyuan
  • Nery, Joseph R.
  • Pinto-Duarte, Antonio
  • Poirion, Olivier B.
  • Preißl, Sebastian
  • Rivkin, Angeline C.
  • Tasic, Bosiljka
  • Zeng, Hongkui
  • Ren, Bing
  • Ecker, Joseph R.
  • Mukamel, Eran A.
  • Universität

Entstanden

  • 2023

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