{"doi":"10.1101/2024.05.17.594606","title":"Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits","abstract":"Epigenome-wide association studies (EWAS) are transforming our understanding of the interplay between epigenetics and complex human traits and phenotypes. We introduce the Methylation Screening Array (MSA), a new iteration of the Infinium technology for scalable and quantitative screening of trait associations of nuanced ternary-code cytosine modifications in larger, more inclusive, and stratified human populations. MSA integrates EWAS, single-cell, and cell-type-resolved methylome profiles, covering diverse human traits and diseases. Our first MSA applications yield multiple biological insights: we revealed a previously unappreciated role of 5-hydroxymethylcytosine (5hmC) in trait associations and epigenetic clocks. We demonstrated that 5hmCs complement 5-methylcytosines (5mCs) in defining tissues and cells' epigenetic identities. In-depth analyses highlighted the cell type context of EWAS and GWAS hits. Using this platform, we conducted a comprehensive human 5hmC aging EWAS, discovering tissue-invariant and tissue-specific aging dynamics, including distinct tissue-specific rates of mitotic hyper- and hypomethylation rates. These findings chart a landscape of the complex interplay of the two forms of cytosine modifications in diverse human tissues and their roles in health and disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485167,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.925,"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":1105236,"name":"Cameron Cloud","orcid":null,"position":1,"is_corresponding":false},{"id":984131,"name":"Sol Moe Lee","orcid":"0000-0002-6935-462X","position":2,"is_corresponding":false},{"id":804744,"name":"Bret Barnes","orcid":null,"position":3,"is_corresponding":false},{"id":1328185,"name":"Steven Gruber","orcid":null,"position":4,"is_corresponding":false},{"id":811360,"name":"Elliot Kim","orcid":"0009-0006-7359-602X","position":5,"is_corresponding":false},{"id":305069,"name":"Anita Pottekat","orcid":"0000-0002-2117-6887","position":6,"is_corresponding":false},{"id":1328186,"name":"Max Westphal","orcid":null,"position":7,"is_corresponding":false},{"id":1328187,"name":"Luana McAuliffe","orcid":null,"position":8,"is_corresponding":false},{"id":1160830,"name":"Elisa Majounie","orcid":null,"position":9,"is_corresponding":false},{"id":1328188,"name":"Manesh KalayilManian","orcid":null,"position":10,"is_corresponding":false},{"id":1328189,"name":"Qingdi Zhu","orcid":null,"position":11,"is_corresponding":false},{"id":1318756,"name":"Christine Tran","orcid":"0000-0003-0226-6374","position":12,"is_corresponding":false},{"id":1104106,"name":"Mark Hansen","orcid":"0000-0003-0567-180X","position":13,"is_corresponding":false},{"id":1328190,"name":"Jelena Stojakovic","orcid":null,"position":14,"is_corresponding":false},{"id":998392,"name":"Jared B. Parker","orcid":"0000-0002-3405-1581","position":15,"is_corresponding":false},{"id":260599,"name":"Rahul M. Kohli","orcid":"0000-0002-7689-5678","position":16,"is_corresponding":false},{"id":984138,"name":"Rishi Porecha","orcid":"0000-0001-9844-3587","position":17,"is_corresponding":false},{"id":1022136,"name":"Nicole Renke","orcid":null,"position":18,"is_corresponding":false},{"id":284749,"name":"Wanding Zhou","orcid":"0000-0001-9126-1932","position":19,"is_corresponding":false},{"id":1328184,"name":"David C Goldberg","orcid":null,"position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T02:07:47.633574Z","pmid":"38826316","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":[]}