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

• DOI: 10.1016/j.xgen.2023.100342
• Publication Date: 2023-06-19T14:35:09Z
• Authors: 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; Antonio Pinto-Duarte; Olivier B. Poirion; Sebastian Preissl; Angeline C. Rivkin; Bosiljka Tasic; Hongkui Zeng; Bing Ren; Joseph R. Ecker; Eran A. Mukamel
• Keywords: Epigenome; Genome-wide Association Study; Epigenomics; Linkage Disequilibrium; Genetic Association

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