{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:37:32Z","timestamp":1772253452140,"version":"3.50.1"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clonal hematopoiesis (CH) of indeterminate potential (CHIP), driven by somatic mutations in leukemia-associated genes, confers increased risk of hematologic malignancies, cardiovascular disease, and all-cause mortality. In blood of healthy individuals, small CH clones can expand over time to reach 2% variant allele frequency (VAF), the current threshold for CHIP. Nevertheless, reliable detection of low-VAF CHIP mutations is challenging, often relying on deep targeted sequencing. Here, we present UNISOM, a streamlined workflow for enhancing CHIP detection from whole-genome and whole-exome sequencing data that are underpowered, especially for low VAFs. UNISOM utilizes a meta-caller for variant detection, in couple with machine learning models which classify variants into CHIP, germline, and artifact. In whole-exome sequencing data, UNISOM recovered nearly 80% of the CHIP mutations identified via deep targeted sequencing in the same cohort. Applied to whole-genome sequencing data from Mayo Clinic Biobank, it recapitulated the patterns previously established in much larger cohorts, including the most frequently mutated CHIP genes and predominant mutation types and signatures, as well as strong associations of CHIP with age and smoking status. Notably, 30% of the identified CHIP mutations had &amp;lt; 5% VAFs, demonstrating its high sensitivity toward small mutant clones. This workflow is applicable to CHIP screening in population genomic studies. The UNISOM pipeline is freely available at https:\/\/github.com\/shulanmayo\/UNISOM and https:\/\/ngdc.cncb.ac.cn\/biocode\/tool\/7816.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzaf040","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T15:43:38Z","timestamp":1745941418000},"source":"Crossref","is-referenced-by-count":1,"title":["UNISOM: Unified Somatic Calling and Machine Learning-based Classification Enhance the Discovery of CHIP"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-7439","authenticated-orcid":false,"given":"Shulan","family":"Tian","sequence":"first","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-098X","authenticated-orcid":false,"given":"Garrett","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4883-3023","authenticated-orcid":false,"given":"Alejandro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-2922","authenticated-orcid":false,"given":"Huihuang","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7710-2211","authenticated-orcid":false,"given":"Joel A","family":"Morales-Rosado","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, TN 37232,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4602-8065","authenticated-orcid":false,"given":"Kevin L","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0315-5230","authenticated-orcid":false,"given":"Terra L","family":"Lasho","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4373-1279","authenticated-orcid":false,"given":"Benjamin B","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Stanford University , Stanford, CA 94305,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3564-7627","authenticated-orcid":false,"given":"Saurabh","family":"Baheti","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-7789","authenticated-orcid":false,"given":"Janet E","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5229-4897","authenticated-orcid":false,"given":"Linda B","family":"Baughn","sequence":"additional","affiliation":[{"name":"Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9811-4601","authenticated-orcid":false,"given":"Wei","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-4712","authenticated-orcid":false,"given":"Susan L","family":"Slager","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-662X","authenticated-orcid":false,"given":"Mrinal S","family":"Patnaik","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-681X","authenticated-orcid":false,"given":"Konstantinos N","family":"Lazaridis","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-5795","authenticated-orcid":false,"given":"Eric W","family":"Klee","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"2025092421563115400_qzaf040-B1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1182\/blood-2015-03-631747","article-title":"Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes","volume":"126","author":"Steensma","year":"2015","journal-title":"Blood"},{"key":"2025092421563115400_qzaf040-B2","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.mayocp.2018.04.002","article-title":"Clinical implications of clonal hematopoiesis","volume":"93","author":"Steensma","year":"2018","journal-title":"Mayo Clin Proc"},{"key":"2025092421563115400_qzaf040-B3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.jacc.2019.05.045","article-title":"Clonal hematopoiesis of indeterminate potential reshapes age-related CVD:\u00a0JACC\u00a0Review Topic of the Week","volume":"74","author":"Khetarpal","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2025092421563115400_qzaf040-B4","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41586-020-2819-2","article-title":"Inherited causes of clonal haematopoiesis in 97,691 whole genomes","volume":"586","author":"Bick","year":"2020","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B5","doi-asserted-by":"crossref","DOI":"10.1126\/science.aan4673","article-title":"Clonal hematopoiesis in human aging and disease","volume":"366","author":"Jaiswal","year":"2019","journal-title":"Science"},{"key":"2025092421563115400_qzaf040-B6","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.3324\/haematol.2018.215269","article-title":"Clonal hematopoiesis and risk of acute myeloid leukemia","volume":"104","author":"Young","year":"2019","journal-title":"Haematologica"},{"key":"2025092421563115400_qzaf040-B7","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N Engl J Med"},{"key":"2025092421563115400_qzaf040-B8","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMoa1409405","article-title":"Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence","volume":"371","author":"Genovese","year":"2014","journal-title":"N Engl J Med"},{"key":"2025092421563115400_qzaf040-B9","doi-asserted-by":"crossref","first-page":"12484","DOI":"10.1038\/ncomms12484","article-title":"Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults","volume":"7","author":"Young","year":"2016","journal-title":"Nat Commun"},{"key":"2025092421563115400_qzaf040-B10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1701719","article-title":"Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease","volume":"377","author":"Jaiswal","year":"2017","journal-title":"N Engl J Med"},{"key":"2025092421563115400_qzaf040-B11","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1200\/JCO.2016.71.6712","article-title":"Clonal hematopoiesis associated with adverse outcomes after autologous stem-cell transplantation for lymphoma","volume":"35","author":"Gibson","year":"2017","journal-title":"J Clin Oncol"},{"key":"2025092421563115400_qzaf040-B12","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1038\/s41467-020-16805-5","article-title":"Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant","volume":"11","author":"Mouhieddine","year":"2020","journal-title":"Nat Commun"},{"key":"2025092421563115400_qzaf040-B13","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41591-018-0081-z","article-title":"Somatic mutations precede acute myeloid leukemia years before diagnosis","volume":"24","author":"Desai","year":"2018","journal-title":"Nat Med"},{"key":"2025092421563115400_qzaf040-B14","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41586-018-0317-6","article-title":"Prediction of acute myeloid leukaemia risk in healthy individuals","volume":"559","author":"Abelson","year":"2018","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B15","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41586-021-04312-6","article-title":"Life histories of myeloproliferative neoplasms inferred from phylogenies","volume":"602","author":"Williams","year":"2022","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41586-022-04785-z","article-title":"The longitudinal dynamics and natural history of clonal haematopoiesis","volume":"606","author":"Fabre","year":"2022","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12979-022-00278-9","article-title":"Longitudinal profiling of clonal hematopoiesis provides insight into clonal dynamics","volume":"19","author":"Uddin","year":"2022","journal-title":"Immun Ageing"},{"key":"2025092421563115400_qzaf040-B18","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/d41586-022-01304-y","article-title":"Blood\u2019s life history traced through genomic scars","volume":"606","author":"Sekar","year":"2022","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B19","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1182\/blood-2017-02-769869","article-title":"Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly","volume":"130","author":"Zink","year":"2017","journal-title":"Blood"},{"key":"2025092421563115400_qzaf040-B20","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1182\/bloodadvances.2024012929","article-title":"Impact of cancer therapy on clonal hematopoiesis mutations and subsequent clinical outcomes","volume":"8","author":"Nead","year":"2024","journal-title":"Blood Adv"},{"key":"2025092421563115400_qzaf040-B21","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.stem.2017.07.010","article-title":"Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes","volume":"21","author":"Coombs","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2025092421563115400_qzaf040-B22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41586-022-04786-y","article-title":"Clonal dynamics of haematopoiesis across the human lifespan","volume":"606","author":"Mitchell","year":"2022","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ajhg.2017.05.013","article-title":"Ultra-sensitive sequencing identifies high prevalence of clonal hematopoiesis-associated mutations throughout adult life","volume":"101","author":"Acuna-Hidalgo","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2025092421563115400_qzaf040-B24","first-page":"2214","article-title":"A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic data sets","volume":"141","author":"Vlasschaert","year":"2023","journal-title":"Blood"},{"key":"2025092421563115400_qzaf040-B25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/gm495","article-title":"Detecting somatic point mutations in cancer genome sequencing data: a comparison of mutation callers","volume":"5","author":"Wang","year":"2013","journal-title":"Genome Med"},{"key":"2025092421563115400_qzaf040-B26","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/1471-2164-15-244","article-title":"Comparison of somatic mutation calling methods in amplicon and whole exome sequence data","volume":"15","author":"Xu","year":"2014","journal-title":"BMC Genomics"},{"key":"2025092421563115400_qzaf040-B27","doi-asserted-by":"crossref","first-page":"e0151664","DOI":"10.1371\/journal.pone.0151664","article-title":"Evaluation of nine somatic variant callers for detection of somatic mutations in exome and targeted deep sequencing data","volume":"11","author":"Kr\u00f8ig\u00e5rd","year":"2016","journal-title":"PLoS One"},{"key":"2025092421563115400_qzaf040-B28","doi-asserted-by":"crossref","first-page":"36540","DOI":"10.1038\/srep36540","article-title":"In-depth comparison of somatic point mutation callers based on different tumor next-generation sequencing depth data","volume":"6","author":"Cai","year":"2016","journal-title":"Sci Rep"},{"key":"2025092421563115400_qzaf040-B29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s13059-015-0758-2","article-title":"An ensemble approach to accurately detect somatic mutations using SomaticSeq","volume":"16","author":"Fang","year":"2015","journal-title":"Genome Biol"},{"key":"2025092421563115400_qzaf040-B30","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.1038\/s41467-020-18151-y","article-title":"Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples","volume":"11","author":"Bailey","year":"2020","journal-title":"Nat Commun"},{"key":"2025092421563115400_qzaf040-B31","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cels.2018.03.002","article-title":"Scalable open science approach for mutation calling of tumor exomes using multiple genomic pipelines","volume":"6","author":"Ellrott","year":"2018","journal-title":"Cell Syst"},{"key":"2025092421563115400_qzaf040-B32","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","article-title":"Pan-cancer analysis of whole genomes","volume":"578","author":"Campbell","year":"2020","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B33","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.tig.2018.04.003","article-title":"Detecting somatic mutations in normal cells","volume":"34","author":"Dou","year":"2018","journal-title":"Trends Genet"},{"key":"2025092421563115400_qzaf040-B34","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1038\/nm.3733","article-title":"Age-related mutations associated with clonal hematopoietic expansion and malignancies","volume":"20","author":"Xie","year":"2014","journal-title":"Nat Med"},{"key":"2025092421563115400_qzaf040-B35","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1038\/s41375-024-02253-3","article-title":"Dynamics of clonal hematopoiesis under DNA-damaging treatment in patients with ovarian cancer","volume":"38","author":"Arends","year":"2024","journal-title":"Leukemia"},{"key":"2025092421563115400_qzaf040-B36","doi-asserted-by":"crossref","first-page":"e2319364121","DOI":"10.1073\/pnas.2319364121","article-title":"The impact of age and number of mutations on the size of clonal hematopoiesis","volume":"121","author":"Wang","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025092421563115400_qzaf040-B37","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1038\/s41591-021-01521-4","article-title":"Distinction of lymphoid and myeloid clonal hematopoiesis","volume":"27","author":"Niroula","year":"2021","journal-title":"Nat Med"},{"key":"2025092421563115400_qzaf040-B38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s42003-018-0023-9","article-title":"Genome-wide somatic variant calling using localized colored de Bruijn graphs","volume":"1","author":"Narzisi","year":"2018","journal-title":"Commun Biol"},{"key":"2025092421563115400_qzaf040-B39","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s12859-021-04185-6","article-title":"2-kupl: mapping-free variant detection from DNA-seq data of matched samples","volume":"22","author":"Wang","year":"2021","journal-title":"BMC Bioinformatics"},{"key":"2025092421563115400_qzaf040-B40","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1093\/nar\/gkx024","article-title":"MosaicHunter: accurate detection of postzygotic single-nucleotide mosaicism through next-generation sequencing of unpaired, trio, and paired samples","volume":"45","author":"Huang","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2025092421563115400_qzaf040-B41","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/s41587-022-01559-w","article-title":"Control-independent mosaic single nucleotide variant detection with DeepMosaic","volume":"41","author":"Yang","year":"2023","journal-title":"Nat Biotechnol"},{"key":"2025092421563115400_qzaf040-B42","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41587-019-0368-8","article-title":"Accurate detection of mosaic variants in sequencing data without matched controls","volume":"38","author":"Dou","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2025092421563115400_qzaf040-B43","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1038\/s41592-023-02043-2","article-title":"Comprehensive benchmarking and guidelines of mosaic variant calling strategies","volume":"20","author":"Ha","year":"2023","journal-title":"Nat Methods"},{"key":"2025092421563115400_qzaf040-B44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41597-022-01133-8","article-title":"Establishment of reference standards for multifaceted mosaic variant analysis","volume":"9","author":"Ha","year":"2022","journal-title":"Sci Data"},{"key":"2025092421563115400_qzaf040-B45","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nbt.2835","article-title":"Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls","volume":"32","author":"Zook","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2025092421563115400_qzaf040-B46","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41587-019-0074-6","article-title":"An open resource for accurately benchmarking small variant and reference calls","volume":"37","author":"Zook","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2025092421563115400_qzaf040-B47","doi-asserted-by":"crossref","first-page":"20222","DOI":"10.1038\/s41598-020-77218-4","article-title":"Accuracy and efficiency of germline variant calling pipelines for human genome data","volume":"10","author":"Zhao","year":"2020","journal-title":"Sci Rep"},{"key":"2025092421563115400_qzaf040-B48","article-title":"PrecisionFDA Truth Challenge V2: calling variants from short and long reads in difficult-to-map regions","author":"Olson","journal-title":"Cell Genom"},{"key":"2025092421563115400_qzaf040-B49","doi-asserted-by":"crossref","first-page":"9345","DOI":"10.1038\/s41598-019-45835-3","article-title":"Systematic comparison of germline variant calling pipelines cross multiple next-generation sequencers","volume":"9","author":"Chen","year":"2019","journal-title":"Sci Rep"},{"key":"2025092421563115400_qzaf040-B50","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nmeth.3407","article-title":"Combining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection","volume":"12","author":"Ewing","year":"2015","journal-title":"Nat Methods"},{"key":"2025092421563115400_qzaf040-B51","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2025092421563115400_qzaf040-B52","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/ng.3343","article-title":"Paired exome analysis of Barrett\u2019s esophagus and adenocarcinoma","volume":"47","author":"Stachler","year":"2015","journal-title":"Nat Genet"},{"key":"2025092421563115400_qzaf040-B53","author":"Garrison"},{"key":"2025092421563115400_qzaf040-B54","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nbt.2514","article-title":"Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples","volume":"31","author":"Cibulskis","year":"2013","journal-title":"Nat Biotechnol"},{"key":"2025092421563115400_qzaf040-B55","doi-asserted-by":"crossref","DOI":"10.1002\/0471250953.bi1110s43","article-title":"From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Van der Auwera","year":"2013","journal-title":"Curr Protoc Bioinformatics"},{"key":"2025092421563115400_qzaf040-B56","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat Genet"},{"key":"2025092421563115400_qzaf040-B57","doi-asserted-by":"crossref","first-page":"11189","DOI":"10.1093\/nar\/gks918","article-title":"LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets","volume":"40","author":"Wilm","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2025092421563115400_qzaf040-B58","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/ng.3036","article-title":"Integrating mapping-, assembly- and haplotype-based approaches for calling variants in clinical sequencing applications","volume":"46","author":"Rimmer","year":"2014","journal-title":"Nat Genet"},{"key":"2025092421563115400_qzaf040-B59","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41592-018-0051-x","article-title":"Strelka2: fast and accurate calling of germline and somatic variants","volume":"15","author":"Kim","year":"2018","journal-title":"Nat Methods"},{"key":"2025092421563115400_qzaf040-B60","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkw227","article-title":"VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research","volume":"44","author":"Lai","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2025092421563115400_qzaf040-B61","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing","volume":"22","author":"Koboldt","year":"2012","journal-title":"Genome Res"},{"key":"2025092421563115400_qzaf040-B62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.csbj.2018.01.003","article-title":"A review of somatic single nucleotide variant calling algorithms for next-generation sequencing data","volume":"16","author":"Xu","year":"2018","journal-title":"Comput Struct Biotechnol J"},{"key":"2025092421563115400_qzaf040-B63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13073-015-0195-6","article-title":"CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical setting","volume":"7","author":"M\u00fcnz","year":"2015","journal-title":"Genome Med"},{"key":"2025092421563115400_qzaf040-B64","first-page":"1","article-title":"mlr: machine learning in R","volume":"17","author":"Bischl","year":"2016","journal-title":"J Mach Learn Res"},{"key":"2025092421563115400_qzaf040-B65","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1182\/blood.2020006910","article-title":"Identifying potential germline variants from sequencing hematopoietic malignancies","volume":"136","author":"Kraft","year":"2020","journal-title":"Blood"},{"key":"2025092421563115400_qzaf040-B66","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.mayocp.2013.06.006","article-title":"The Mayo Clinic Biobank: a building block for individualized medicine","volume":"88","author":"Olson","year":"2013","journal-title":"Mayo Clin Proc"},{"key":"2025092421563115400_qzaf040-B67","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s00401-019-01962-9","article-title":"Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD","volume":"137","author":"Pottier","year":"2019","journal-title":"Acta Neuropathol"},{"key":"2025092421563115400_qzaf040-B68","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1093\/bioinformatics\/btu356","article-title":"Toward better understanding of artifacts in variant calling from high-coverage samples","volume":"30","author":"Li","year":"2014","journal-title":"Bioinformatics"},{"key":"2025092421563115400_qzaf040-B69","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1001\/jamacardio.2018.3965","article-title":"Association of mutations contributing to clonal hematopoiesis with prognosis in chronic ischemic heart failure","volume":"4","author":"Dorsheimer","year":"2019","journal-title":"JAMA Cardiol"},{"key":"2025092421563115400_qzaf040-B70","doi-asserted-by":"crossref","first-page":"21","DOI":"10.12688\/wellcomeopenres.13538.1","article-title":"Evaluating the performance of tools used to call minority variants from whole genome short-read data","volume":"3","author":"Said Mohammed","year":"2018","journal-title":"Wellcome Open Res"},{"key":"2025092421563115400_qzaf040-B71","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1186\/s12864-016-3045-z","article-title":"An analytical workflow for accurate variant discovery in highly divergent regions","volume":"17","author":"Tian","year":"2016","journal-title":"BMC Genomics"},{"key":"2025092421563115400_qzaf040-B72","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00439-015-1631-9","article-title":"Clinical sequencing: is WGS the better WES?","volume":"135","author":"Meienberg","year":"2016","journal-title":"Hum Genet"},{"key":"2025092421563115400_qzaf040-B73","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1073\/pnas.1418631112","article-title":"Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants","volume":"112","author":"Belkadi","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025092421563115400_qzaf040-B74","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13073-014-0089-z","article-title":"Reducing INDEL calling errors in whole genome and exome sequencing data","volume":"6","author":"Fang","year":"2014","journal-title":"Genome Med"},{"key":"2025092421563115400_qzaf040-B75","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/nbt.3966","article-title":"Analysis of somatic microsatellite indels identifies driver events in human tumors","volume":"35","author":"Maruvka","year":"2017","journal-title":"Nat Biotechnol"},{"key":"2025092421563115400_qzaf040-B76","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1038\/s41467-022-31397-y","article-title":"Ultra-sensitive monitoring of leukemia patients using superRCA mutation detection assays","volume":"13","author":"Chen","year":"2022","journal-title":"Nat Commun"},{"key":"2025092421563115400_qzaf040-B77","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1038\/s41375-018-0193-y","article-title":"Discriminating a common somatic\u00a0ASXL1\u00a0mutation (c.1934dup; p.G646Wfs*12) from artifact in myeloid malignancies using NGS","volume":"32","author":"Alberti","year":"2018","journal-title":"Leukemia"},{"key":"2025092421563115400_qzaf040-B78","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.17929","article-title":"TP53\u00a0exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions","volume":"5","author":"Shirole","year":"2016","journal-title":"Elife"},{"key":"2025092421563115400_qzaf040-B79","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1126\/science.aax3649","article-title":"A dominant-negative effect drives selection of\u00a0TP53\u00a0missense mutations in myeloid malignancies","volume":"365","author":"Boettcher","year":"2019","journal-title":"Science"},{"key":"2025092421563115400_qzaf040-B80","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cell.2012.06.023","article-title":"The origin and evolution of mutations in acute myeloid leukemia","volume":"150","author":"Welch","year":"2012","journal-title":"Cell"},{"key":"2025092421563115400_qzaf040-B81","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B82","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1158\/2643-3230.BCD-20-0094","article-title":"Large-scale identification of clonal hematopoiesis and mutations recurrent in blood cancers","volume":"2","author":"Feusier","year":"2021","journal-title":"Blood Cancer Discov"},{"key":"2025092421563115400_qzaf040-B83","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13059-019-1659-6","article-title":"Analysis of error profiles in deep next-generation sequencing data","volume":"20","author":"Ma","year":"2019","journal-title":"Genome Biol"},{"key":"2025092421563115400_qzaf040-B84","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1152\/physrev.00004.2022","article-title":"Clonal hematopoiesis, somatic mosaicism, and age-associated disease","volume":"103","author":"Evans","year":"2023","journal-title":"Physiol Rev"},{"key":"2025092421563115400_qzaf040-B85","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/s41591-022-01883-3","article-title":"Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects","volume":"28","author":"Robertson","year":"2022","journal-title":"Nat Med"},{"key":"2025092421563115400_qzaf040-B86","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13045-021-01169-0","article-title":"Targeting mutant p53 for cancer therapy: direct and indirect strategies","volume":"14","author":"Hu","year":"2021","journal-title":"J Hematol Oncol"},{"key":"2025092421563115400_qzaf040-B87","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nature13968","article-title":"Role of\u00a0TP53\u00a0mutations in the origin and evolution of therapy-related acute myeloid leukaemia","volume":"518","author":"Wong","year":"2015","journal-title":"Nature"},{"key":"2025092421563115400_qzaf040-B88","doi-asserted-by":"crossref","first-page":"6005","DOI":"10.1073\/pnas.1601311113","article-title":"Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic\u00a0TP53\u00a0mutations in noncancerous tissues","volume":"113","author":"Krimmel","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025092421563115400_qzaf040-B89","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/leu.2015.17","article-title":"Quantifying ultra-rare pre-leukemic clones via targeted error-corrected sequencing","volume":"29","author":"Young","year":"2015","journal-title":"Leukemia"},{"key":"2025092421563115400_qzaf040-B90","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.celrep.2019.05.109","article-title":"Ultra-sensitive\u00a0TP53\u00a0sequencing for cancer detection reveals progressive clonal selection in normal tissue over a century of human lifespan","volume":"28","author":"Salk","year":"2019","journal-title":"Cell Rep"}],"container-title":["Genomics, Proteomics &amp; Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/gpb\/advance-article-pdf\/doi\/10.1093\/gpbjnl\/qzaf040\/63029131\/qzaf040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/article-pdf\/23\/2\/qzaf040\/63029131\/qzaf040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/article-pdf\/23\/2\/qzaf040\/63029131\/qzaf040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T01:56:50Z","timestamp":1758765410000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/gpb\/article\/doi\/10.1093\/gpbjnl\/qzaf040\/8121950"}},"subtitle":[],"editor":[{"given":"Qian-Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":90,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,5,30]]}},"URL":"https:\/\/doi.org\/10.1093\/gpbjnl\/qzaf040","relation":{},"ISSN":["1672-0229","2210-3244"],"issn-type":[{"value":"1672-0229","type":"print"},{"value":"2210-3244","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,4]]},"article-number":"qzaf040"}}