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While epigenetic mechanisms are widely implicated in gene expression regulation, a definitive link between chromatin accessibility and scEV remains elusive. Recent advances in single-cell techniques enable the study of single-cell multiomics data that include the simultaneous measurement of scATAC-seq and scRNA-seq within individual cells, presenting an unprecedented opportunity to address this gap.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This article introduces an innovative testing pipeline to investigate the association between chromatin accessibility and scEV. With single-cell multiomics data of scATAC-seq and scRNA-seq, the pipeline hinges on comparing the prediction performance of scATAC-seq data on gene expression levels between highly variable genes (HVGs) and non-highly variable genes (non-HVGs). Applying this pipeline to paired scATAC-seq and scRNA-seq data from human hematopoietic stem and progenitor cells, we observed a significantly superior prediction performance of scATAC-seq data for HVGs compared to non-HVGs. Notably, there was a substantial overlap between well-predicted genes and HVGs. The gene pathways enriched from well-predicted genes are highly pertinent to cell type-specific functions. Our findings support the notion that scEV largely stems from cell-to-cell variability in chromatin accessibility, providing compelling evidence for the epigenetic regulation of scEV and offering promising avenues for investigating gene regulation mechanisms at the single-cell level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code and data used in this article can be found at https:\/\/github.com\/SiweiCui\/EpigeneticControlOfSingle-CellExpressionVariability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae457","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T12:13:40Z","timestamp":1721218420000},"source":"Crossref","is-referenced-by-count":4,"title":["Controlled noise: evidence of epigenetic regulation of single-cell expression variability"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-043X","authenticated-orcid":false,"given":"Yan","family":"Zhong","sequence":"first","affiliation":[{"name":"School of Statistics, KLATASDS-MOE, East China Normal University , Shanghai, 200062, China"}]},{"given":"Siwei","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Statistics, KLATASDS-MOE, East China Normal University , Shanghai, 200062, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4135-5014","authenticated-orcid":false,"given":"Yongjian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas A&M University , College Station, TX 77843, United States"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8081-6725","authenticated-orcid":false,"given":"James J","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas A&M University , College Station, TX 77843, United States"},{"name":"Department of Veterinary Integrative Biosciences, Texas A&M University , College Station, TX 77843, United States"},{"name":"Interdisciplinary Program of Genetics, Texas A&M University , College Station, TX 77843, United States"}]}],"member":"286","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"2024072719125354800_btae457-B1","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202302415","article-title":"MICA: a multi-omics method to predict gene regulatory networks in early human embryos","volume":"7","author":"Alanis-Lobato","year":"2024","journal-title":"Life Sci Alliance"},{"key":"2024072719125354800_btae457-B2","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature14590","article-title":"Single-cell chromatin accessibility reveals principles of regulatory variation","volume":"523","author":"Buenrostro","year":"2015","journal-title":"Nature"},{"key":"2024072719125354800_btae457-B3","author":"Burkhardt","year":"2022"},{"key":"2024072719125354800_btae457-B4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2024072719125354800_btae457-B5","volume-title":"Bioinformatics","author":"Cai","year":"2020"},{"key":"2024072719125354800_btae457-B6","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1126\/science.aau0730","article-title":"Joint profiling of chromatin accessibility and gene expression in thousands of single cells","volume":"361","author":"Cao","year":"2018","journal-title":"Science"},{"key":"2024072719125354800_btae457-B7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3389\/fgene.2014.00075","article-title":"Impact of artifact removal on ChIP quality metrics in ChIP-seq and ChIP-exo data","volume":"5","author":"Carroll","year":"2014","journal-title":"Front Genet"},{"key":"2024072719125354800_btae457-B8","volume-title":"Introduction to Modern Information Retrieval","author":"Chowdhury","year":"2010"},{"key":"2024072719125354800_btae457-B9","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/bies.201500124","article-title":"Variation is function: are single cell differences functionally important? 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