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

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

doi:10.1016/j.xgen.2023.100342

BioinformaticsCell GenomicsJun 19, 2023

Peer-reviewed journal article

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

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

Abstract

Integrating single-cell transcriptomes and epigenomes across diverse cell types can link genes with the cis-regulatory elements (CREs) that control expression. Gene co-expression across cell types confounds simple correlation-based analysis and results in high false prediction rates. We developed a procedure that controls for co-expression between genes and integrates multiple molecular modalities, and used it to identify >10,000 gene-CRE pairs that contribute to gene expression programs in different cell types in the mouse brain.

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