{"doi":"10.1016/j.celrep.2025.115755","title":"Complete reference genome and pangenome improve genome-wide detection and interpretation of DNA methylation using sequencing and array data","abstract":"The complete telomere-to-telomere human genome assembly (T2T-CHM13) and the draft human pangenome reference provide unique opportunities to refine DNA methylation (DNAm) studies. Here, we find that T2T-CHM13 calls 7.4% more CpGs genome wide compared to GRCh38 across four widely used short-read DNAm profiling methods and improves the evaluation of probe cross-reactivity and mismatch for Illumina DNAm arrays, yielding new and more reproducible sets of unambiguous probes. The pangenome reference further expands CpG calling by 4.5% in short-read sequencing data and identifies cross-population and population-specific unambiguous probes in DNAm arrays, owing to its improved representation of genetic diversity. These benefits facilitate the discovery of biologically relevant DNAm alterations in epigenome-wide association studies (EWASs). For instance, additional DNAm alterations enriched in cancer-related genes and pathways are identified in cancer EWASs. Together, this study highlights the practical applications of T2T-CHM13 and pangenome for genome biology and provides a basis for expansion of DNAm investigations.","journal":"Cell Reports","year":2025,"id":541311,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5975,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1328627,"name":"Joanne Whitehead","orcid":"0000-0002-9602-2081","position":1,"is_corresponding":false},{"id":1334150,"name":"Xiaoqing Fu","orcid":"0000-0002-3694-122X","position":2,"is_corresponding":false},{"id":1383850,"name":"Julia L. MacIsaac","orcid":"0000-0001-9063-5429","position":3,"is_corresponding":false},{"id":11021,"name":"David H. Rehkopf","orcid":"0000-0002-7597-6513","position":4,"is_corresponding":false},{"id":856624,"name":"Luis Rosero‐Bixby","orcid":"0000-0002-3063-3111","position":5,"is_corresponding":false},{"id":5180,"name":"Michael S. Kobor","orcid":"0000-0003-4140-1743","position":6,"is_corresponding":false},{"id":37159,"name":"Keegan Korthauer","orcid":"0000-0002-4565-1654","position":7,"is_corresponding":false},{"id":1429668,"name":"Zheng Dong","orcid":"0000-0002-2850-0002","position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T02:52:47.161928Z","pmid":"40445831","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":[]}