{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:03:14Z","timestamp":1774893794330,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ontario Institute for Cancer Research with funds from the province of Ontario and by the University of Toronto\u2019s Medicine by Design initiative"},{"DOI":"10.13039\/501100010785","name":"Canada First Research Excellence Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010785","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Canadian Institutes of Health Research Doctoral Award: Frederick Banting and Charles Best Canada Graduate Scholarships","award":["FBD-170928"],"award-info":[{"award-number":["FBD-170928"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Single-molecule molecular inversion probes (smMIPs) provide an exceptionally cost-effective and modular approach for routine or large-cohort next-generation sequencing. However, processing the derived raw data to generate highly accurate variants calls remains challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We introduce SmMIP-tools, a comprehensive computational method that promotes the detection of single nucleotide variants and short insertions and deletions from smMIP-based sequencing. Our approach delivered near-perfect performance when benchmarked against a set of known mutations in controlled experiments involving DNA dilutions and outperformed other commonly used computational methods for mutation detection. Comparison against clinically approved diagnostic testing of leukaemia patients demonstrated the ability to detect both previously reported variants and a set of pathogenic mutations that did not pass detection by clinical testing. Collectively, our results indicate that increased performance can be achieved when tailoring data processing and analysis to its related technology. The feasibility of using our method in research and clinical settings to benefit from low-cost smMIP technology is demonstrated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code for SmMIP-tools, its manual and additional scripts aimed to foster large-scale data processing and analysis are all available on github (https:\/\/github.com\/abelson-lab\/smMIP-tools). Raw sequencing data generated in this study have been submitted to the European Genome-Phenome Archive (EGA; https:\/\/ega-archive.org) and can be accessed under accession number EGAS00001005359.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btac081","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T15:12:18Z","timestamp":1644246738000},"page":"2088-2095","source":"Crossref","is-referenced-by-count":11,"title":["SmMIP-tools: a computational toolset for processing and analysis of single-molecule molecular inversion probes-derived data"],"prefix":"10.1093","volume":"38","author":[{"given":"Jessie J F","family":"Medeiros","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network (UHN) , Toronto, ON, Canada"},{"name":"Ontario Institute for Cancer Research , Toronto, ON, Canada"},{"name":"Department of Molecular Genetics, University of Toronto , Toronto, ON, Canada"}]},{"given":"Jose-Mario","family":"Capo-Chichi","sequence":"additional","affiliation":[{"name":"Genome Diagnostics, Department of Clinical Laboratory Genetics, University Health Network , Toronto, ON, Canada"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3700-270X","authenticated-orcid":false,"given":"Liran I","family":"Shlush","sequence":"additional","affiliation":[{"name":"Department of Immunology, Weizmann Institute of Science , Rehovot, Israel"}]},{"given":"John E","family":"Dick","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network (UHN) , Toronto, ON, Canada"},{"name":"Department of Molecular Genetics, University of Toronto , Toronto, ON, Canada"}]},{"given":"Andrea","family":"Arruda","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network (UHN) , Toronto, ON, Canada"}]},{"given":"Mark D","family":"Minden","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network (UHN) , Toronto, ON, Canada"},{"name":"Department of Hematology and Medical Oncology, University Health Network , Toronto, ON, Canada"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1747-3819","authenticated-orcid":false,"given":"Sagi","family":"Abelson","sequence":"additional","affiliation":[{"name":"Ontario Institute for Cancer Research , Toronto, ON, Canada"},{"name":"Department of Molecular Genetics, University of Toronto , Toronto, ON, Canada"}]}],"member":"286","published-online":{"date-parts":[[2022,2,12]]},"reference":[{"key":"2023020109023993700_btac081-B1","author":"Abdallah","year":"2020"},{"key":"2023020109023993700_btac081-B2","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":"2023020109023993700_btac081-B3","doi-asserted-by":"crossref","first-page":"eabe3722","DOI":"10.1126\/sciadv.abe3722","article-title":"Integration of intra-sample contextual error modeling for improved detection of somatic mutations from deep sequencing","volume":"6","author":"Abelson","year":"2020","journal-title":"Sci. Adv"},{"key":"2023020109023993700_btac081-B6","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1093\/bioinformatics\/btu353","article-title":"MIPgen: optimized modeling and design of molecular inversion probes for targeted resequencing","volume":"30","author":"Boyle","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020109023993700_btac081-B8","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1186\/s12864-018-4703-0","article-title":"Characterization and remediation of sample index swaps by non-redundant dual indexing on massively parallel sequencing platforms","volume":"19","author":"Costello","year":"2018","journal-title":"BMC Genomics"},{"key":"2023020109023993700_btac081-B9","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":"2023020109023993700_btac081-B10","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jbiotec.2016.12.022","article-title":"Application of next generation sequencing in clinical microbiology and infection prevention","volume":"243","author":"Deurenberg","year":"2017","journal-title":"J. Biotechnol"},{"key":"2023020109023993700_btac081-B11","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":"2023020109023993700_btac081-B12","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1146\/annurev-genom-090413-025341","article-title":"Noninvasive prenatal screening by next-generation sequencing","volume":"15","author":"Gregg","year":"2014","journal-title":"Annu. Rev. Genomics Hum. Genet"},{"key":"2023020109023993700_btac081-B13","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1101\/gr.147686.112","article-title":"Single molecule molecular inversion probes for targeted, high accuracy detection of low frequency variation","volume":"23","author":"Hiatt","year":"2013","journal-title":"Genome Res"},{"key":"2023020109023993700_btac081-B14","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":"2023020109023993700_btac081-B15","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":"2023020109023993700_btac081-B16","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/PPO.0000000000000385","article-title":"Clinical applications of next-generation sequencing in precision oncology","volume":"25","author":"Karlovich","year":"2019","journal-title":"Cancer J"},{"key":"2023020109023993700_btac081-B18","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":"2023020109023993700_btac081-B19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13073-020-00791-w","article-title":"Best practices for variant calling in clinical sequencing","volume":"12","author":"Koboldt","year":"2020","journal-title":"Genome Med"},{"key":"2023020109023993700_btac081-B20","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":"2023020109023993700_btac081-B21","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":"2023020109023993700_btac081-B22","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nmeth.1419","article-title":"Target-enrichment strategies for next-generation sequencing","volume":"7","author":"Mamanova","year":"2010","journal-title":"Nat. Methods"},{"key":"2023020109023993700_btac081-B24","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1126\/science.1227764","article-title":"Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders","volume":"338","author":"O\u2019Roak","year":"2012","journal-title":"Science"},{"key":"2023020109023993700_btac081-B25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nmeth1110","article-title":"Multiplex amplification of large sets of human exons","volume":"4","author":"Porreca","year":"2007","journal-title":"Nat. Methods"},{"key":"2023020109023993700_btac081-B26","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023020109023993700_btac081-B27","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrg.2017.117","article-title":"Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations","volume":"19","author":"Salk","year":"2018","journal-title":"Nat. Rev. Genet"},{"key":"2023020109023993700_btac081-B31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nmeth.f.248","article-title":"Massively parallel exon capture and library-free resequencing across 16 genomes","volume":"6","author":"Turner","year":"2009","journal-title":"Nat. Methods"},{"key":"2023020109023993700_btac081-B32","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"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btac081\/42559131\/btac081.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/38\/8\/2088\/49010070\/btac081.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/38\/8\/2088\/49010070\/btac081.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T15:52:11Z","timestamp":1675266731000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/38\/8\/2088\/6527628"}},"subtitle":[],"editor":[{"given":"Can","family":"Alkan","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,2,12]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,4,12]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btac081","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.03.446993","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,15]]},"published":{"date-parts":[[2022,2,12]]}}}