{"doi":"10.17615/qqnb-a348","title":"Longitudinal profiling of clonal hematopoiesis provides insight into clonal dynamics","abstract":"Background: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of mutant hematopoietic stem cells, confers risk for multiple diseases of aging including hematologic cancer and cardiovascular disease. Whole-exome or genome sequencing can detect CHIP, but due to those assays’ high cost, most population studies have been cross-sectional, sequencing only a single timepoint per individual. Results: We developed and validated a cost-effective single molecule molecular inversion probe sequencing (smMIPS) assay for detecting CHIP, targeting the 11 most frequently mutated genes in CHIP along with 4 recurrent mutational hotspots. We sequenced 548 multi-timepoint samples collected from 182 participants in the Women’s Health Initiative cohort, across a median span of 16 years. We detected 178 driver mutations reaching variant allele frequency ≥ 2% in at least one timepoint, many of which were detectable well below this threshold at earlier timepoints. The majority of clonal mutations (52.1%) expanded over time (with a median doubling period of 7.43 years), with the others remaining static or decreasing in size in the absence of any cytotoxic therapy. Conclusions: Targeted smMIPS sequencing can sensitively measure clonal dynamics in CHIP. Mutations that reached the conventional threshold for CHIP (2% frequency) tended to continue growing, indicating that after CHIP is acquired, it is generally not lost. The ability to cost-effectively profile CHIP longitudinally will enable future studies to investigate why some CHIP clones expand, and how their dynamics relate to health outcomes at a biobank scale.","journal":"UNC Libraries","year":2024,"id":499494,"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":0.8906,"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":581705,"name":"Pinkal Desai","orcid":"0000-0002-9816-7284","position":1,"is_corresponding":false},{"id":24665,"name":"Pradeep Natarajan","orcid":"0000-0001-8402-7435","position":2,"is_corresponding":false},{"id":11363,"name":"Charles Kooperberg","orcid":"0000-0002-7986-8560","position":3,"is_corresponding":false},{"id":258460,"name":"Kathleen M. Hayden","orcid":"0000-0002-7745-3513","position":4,"is_corresponding":false},{"id":218530,"name":"Bala Bharathi Burugula","orcid":"0000-0003-1114-6964","position":5,"is_corresponding":false},{"id":561964,"name":"Md Mesbah Uddin","orcid":"0000-0003-1846-0411","position":6,"is_corresponding":false},{"id":232179,"name":"Ana Barac","orcid":"0000-0002-9935-8904","position":7,"is_corresponding":false},{"id":27378,"name":"Alexander G. Bick","orcid":"0000-0001-5824-9595","position":8,"is_corresponding":false},{"id":40413,"name":"Jacob O. Kitzman","orcid":"0000-0002-6145-882X","position":9,"is_corresponding":false},{"id":176616,"name":"JO ANN E. MANSON","orcid":null,"position":10,"is_corresponding":false},{"id":1327089,"name":"A.P Reiner","orcid":null,"position":11,"is_corresponding":false},{"id":621763,"name":"Siddhartha Jaiswal","orcid":"0000-0002-9597-0477","position":12,"is_corresponding":false},{"id":1346851,"name":"S.-A.M. Love","orcid":null,"position":13,"is_corresponding":false},{"id":373536,"name":"Michael C. Honigberg","orcid":"0000-0001-8630-5021","position":14,"is_corresponding":false},{"id":14882,"name":"Ying Zhou","orcid":"0000-0002-8107-3927","position":15,"is_corresponding":false},{"id":218550,"name":"Eric A. Whitsel","orcid":"0000-0003-4843-3641","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:53.188165Z","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":[]}