{"doi":"10.1101/2024.10.01.616139","title":"High-coverage allele-resolved single-cell DNA methylation profiling by scDEEP-mC reveals cell lineage, X-inactivation state, and replication dynamics","abstract":"Abstract DNA methylation is a relatively stable epigenetic mark with important roles in development and disease. 1 Since cell-to-cell variation in epigenetic programming can reflect important differences in cell state and fate, it is clear that single-cell methods are essential to understanding this key epigenetic mark in heterogeneous tissues. Existing single-cell whole-genome bisulfite sequencing (scWGBS) methods 2 have significant shortcomings, including very low CpG coverage 3–7 or inefficient library generation requiring extremely deep sequencing. 8 These methods offer limited insight into focal regulatory regions and generally preclude direct cell-to-cell comparisons. To address these shortcomings, we have developed an improved method, scDEEP-mC (single-cell Deep and Efficient Epigenomic Profiling of methyl-C). We show that high-coverage promoter methylation profiling by scDEEP-mC can identify multiple cell types, while allele-resolved methylation calls allow assessment of X-inactivation state in single cells and identification of transcription factor binding sites (TFBS) enriched for hemi-methylation. We also use scDEEP-mC to profile single-cell copy number alterations, identify actively replicating cells, and track DNA methylation dynamics during and after DNA replication. The high coverage of scDEEP-mC creates an exceptional opportunity to explore DNA methylation biology in individual cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":504244,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9394,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":731594,"name":"Walid Abi Habib","orcid":"0000-0001-7017-7854","position":1,"is_corresponding":false},{"id":683341,"name":"Zhouwei Zhang","orcid":"0000-0001-6362-9031","position":2,"is_corresponding":false},{"id":1354805,"name":"Emily Eugster","orcid":null,"position":3,"is_corresponding":false},{"id":1354806,"name":"Hsiao-yun Milliron","orcid":null,"position":4,"is_corresponding":false},{"id":574382,"name":"David Sokol","orcid":null,"position":5,"is_corresponding":false},{"id":984132,"name":"Kwang‐Ho Lee","orcid":"0000-0002-3677-0977","position":6,"is_corresponding":false},{"id":853656,"name":"Paula A. Nolte","orcid":null,"position":7,"is_corresponding":false},{"id":853655,"name":"Jamie L. Endicott","orcid":null,"position":8,"is_corresponding":false},{"id":1354807,"name":"Kelly F. Krzyzanowski","orcid":null,"position":9,"is_corresponding":false},{"id":69739,"name":"Toshinori Hinoue","orcid":"0000-0002-5078-5016","position":10,"is_corresponding":false},{"id":638458,"name":"Jacob Morrison","orcid":"0000-0001-8592-4744","position":11,"is_corresponding":false},{"id":486008,"name":"Benjamin K. Johnson","orcid":"0000-0002-1482-1032","position":12,"is_corresponding":false},{"id":284749,"name":"Wanding Zhou","orcid":"0000-0001-9126-1932","position":13,"is_corresponding":false},{"id":14040,"name":"Hui Shen","orcid":"0000-0001-9767-4084","position":14,"is_corresponding":false},{"id":279356,"name":"Peter W. Laird","orcid":"0000-0001-9117-3641","position":15,"is_corresponding":false},{"id":984135,"name":"Nathan J. Spix","orcid":"0000-0001-6222-0701","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:35.597333Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}