Journal
GENOMICS PROTEOMICS & BIOINFORMATICS
Volume 19, Issue 2, Pages 172-190Publisher
ELSEVIER
DOI: 10.1016/j.gpb.2020.06.010
Keywords
Single-cell ATAC-seq; Gene regulation; Epigenetics; Single-cell multi-omics; Cis-regulatory elements
Categories
Funding
- Vanier Canada Graduate Scholarship
- Killam Doctoral Scholarship
- Alberta Innovates Doctoral Scholarship
- Cancer Research Society award (Scholarships for the New Generation of Scientists)
- Multiple Myeloma Research Foundation
- National Institutes of Health (NIH) [K08CA230188]
- Parker Institute for Cancer Immunotherapy
- Cancer Research Institute Technology Impact Award
- Burroughs Wellcome Fund
- Human Vaccines Project Michelson Prize
- National Human Genome Research Institute of NIH [R01HG009518, R01HG010889]
- Alberta Children's Hospital Research Institute Postdoctoral Fellowship
- Alberta Innovates Summer Studentship
- Canadian Institutes of Health Research [PJT-401394]
- Calgary Firefighters Burn Treatment Society
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The review outlines the molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using scATAC-seq in a scalable fashion. It also covers joint profiling of chromatin with transcriptome/proteome measurements, computational strategies for multi-omic integration, and predictive bioinformatic tools for inferring chromatin accessibility from single-cell transcriptomic datasets. Methodological refinements that increase power for cell discovery and integrate measurements from multiple modalities will further expand understanding of gene regulation during homeostasis and disease.
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.
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