Profiling Chromatin Accessibility at Single-cell Resolution

• Published in: Genomics, proteomics & bioinformatics Vol. 19; no. 2; pp. 172 - 190
• Main Authors: Sinha, Sarthak, Satpathy, Ansuman T., Zhou, Weiqiang, Ji, Hongkai, Stratton, Jo A., Jaffer, Arzina, Bahlis, Nizar, Morrissy, Sorana, Biernaskie, Jeff A.
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.04.2021; Hotchkiss Brain Institute,University of Calgary,Calgary,AB T2N 4N1,Canada%Arnie Charbonneau Cancer Institute,University of Calgary,Calgary,AB T2N 4Z6,Canada%Alberta Children's Hospital Research Institute,University of Calgary,Calgary,AB T2N 4N1,Canada; Alberta Children's Hospital Research Institute,University of Calgary,Calgary,AB T2N 4N1,Canada; Department of Comparative Biology & Experimental Medicine,Faculty of Veterinary Medicine,University of Calgary,Calgary,AB T2N 4N1,Canada%Department of Pathology,Stanford University School of Medicine,Stanford,CA 94305,USA%Department of Biostatistics,Bloomberg School of Public Health,Johns Hopkins University,Baltimore,MD 21205,USA%Department of Comparative Biology & Experimental Medicine,Faculty of Veterinary Medicine,University of Calgary,Calgary,AB T2N 4N1,Canada; Arnie Charbonneau Cancer Institute,University of Calgary,Calgary,AB T2N 4Z6,Canada; Department of Biochemistry and Molecular Biology,Cumming School of Medicine,University of Calgary,Calgary,AB T2N 4N1,Canada; Elsevier; Oxford University Press
• Subjects: bioinformatics; chromatin; Chromatin - genetics; Cis-regulatory elements; Computational Biology; data collection; Epigenetics; epigenome; Gene regulation; genes; Genome; genomics; homeostasis; proteome; proteomics; Review; Single-Cell Analysis; Single-cell ATAC-seq; Single-cell multi-omics; transcription (genetics); Transcriptome; transcriptomics; Transposases - chemistry; Transposases - genetics; Transposases - metabolism; Single-cell ATAC-seq; Epigenetics; Single-cell multi-omics; Cis-regulatory elements; Gene regulation
• ISSN: 1672-0229; 2210-3244
• DOI: 10.1016/j.gpb.2020.06.010

How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity, and enable complex fate decisions are important open questions. One key regulator is the cell’s epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility. Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences (in)accessible to DNA-binding proteins at a single-cell resolution. This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) in a scalable fashion. It also covers joint profiling of chromatin with transcriptome/proteome measurements, computational strategies to integrate multi-omic measurements, and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets. Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.