{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:21:54Z","timestamp":1767180114991,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013443","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000}}],"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["92046009"],"award-info":[{"award-number":["92046009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shaanxi's Natural Science Basic Research Program","award":["2020JC-01"],"award-info":[{"award-number":["2020JC-01"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Molecular residual disease (MRD) detection, initially developed for hematologic malignancies, has become a critical biomarker for monitoring solid tumors. MRD detection primarily relies on circulating tumor DNA (ctDNA) analysis using next-generation sequencing, offering high sensitivity and broad genomic coverage. However, challenges remain in designing cost-effective panels that maximize mutation detection while maintaining biological relevance. Fixed panels often lack sufficient patient-specific mutation coverage, while WES-based personalized MRD assays, despite their high sensitivity, are costly and less accessible. We developed a tumor comprehensive genomic profiling (CGP)-informed personalized MRD assay to detect tumor-derived mutations, which allowed us to design patient-specific personalized panels and meanwhile, provide a cost-effective alternative to whole exome sequencing (WES). To address these limitations, we developed MRDtarget, a heuristic multivariate Gaussian model-based targeted capture region selection method. By expanding beyond traditional hotspot regions, MRDtarget optimizes variant tracking for MRD detection, significantly improving sensitivity. Using a Bayesian inference-based heuristic approach, MRDtarget integrates multi-feature informativeness rates to identify optimal genomic regions for capture. Experimental results demonstrate that MRDtarget enables the detection of more variants per patient. This study underscores the importance of rational panel design to improve MRD sensitivity and provides a novel approach to enhance precision diagnostics and treatment for solid tumor patients.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013443","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T17:41:41Z","timestamp":1758130901000},"page":"e1013443","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["MRDtarget: A heuristic Gaussian approach for optimizing targeted capture regions to enhance Minimal Residual Disease detection"],"prefix":"10.1371","volume":"21","author":[{"given":"Xuwen","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuqiang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shenjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuanying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3862-6557","authenticated-orcid":true,"given":"Jiayin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"issue":"3","key":"pcbi.1013443.ref001","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S1389-0344(00)00073-3","article-title":"Molecular characterization of minimal residual cancer cells in patients with solid tumors","volume":"17","author":"B B\u00f6ckmann","year":"2001","journal-title":"Biomol Eng"},{"issue":"20","key":"pcbi.1013443.ref002","doi-asserted-by":"crossref","first-page":"6026","DOI":"10.1158\/1078-0432.CCR-19-0152","article-title":"Molecular residual disease and adjuvant trial design in solid tumors","volume":"25","author":"M Coakley","year":"2019","journal-title":"Clinical Cancer Research"},{"issue":"3","key":"pcbi.1013443.ref003","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s40291-019-00390-5","article-title":"Detection of solid tumor Molecular Residual Disease (MRD) using Circulating Tumor DNA (ctDNA","volume":"23","author":"R-I Chin","year":"2019","journal-title":"). 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