{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:43:35Z","timestamp":1784123015045,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Center","award":["NCC-2210700"],"award-info":[{"award-number":["NCC-2210700"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null\u2013homozygote (N\u2013H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles. Sensitivity was approximately 20% for in-house results from BB and CC and around 5% for AA. Dynamic Read Analysis for GENomics (DRAGEN) analyses identified 1.34 to 1.71 times more variants, detecting over 96% of in-house variants, with sensitivity for common variants increasing to 5%. In-house FP errors varied significantly among companies (up to 13.97 times), while DRAGEN minimized this variation. Despite DRAGEN showing higher FP errors for BB and CC, the increased sensitivity highlights the importance of effective bioinformatic conditions. We also assessed the potential effects of target enrichment and proposed optimal cutoff values for the read depth and variant allele fraction in WES. Optimizing bioinformatic analysis based on sensitivity and specificity from reference standards can enhance variant detection and improve the clinical utility of WES.<\/jats:p>","DOI":"10.3390\/ijms252413250","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T08:40:10Z","timestamp":1733820010000},"page":"13250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing"],"prefix":"10.3390","volume":"25","author":[{"given":"Youngbeen","family":"Moon","sequence":"first","affiliation":[{"name":"Bioinformatics Analysis Team, Research Core Center, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2361-1635","authenticated-orcid":false,"given":"Chung Hwan","family":"Hong","sequence":"additional","affiliation":[{"name":"Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-0906","authenticated-orcid":false,"given":"Young-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Diagnostic and Therapeutics Technology Branch, Division of Technology Convergence, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9290-0820","authenticated-orcid":false,"given":"Jong-Kwang","family":"Kim","sequence":"additional","affiliation":[{"name":"Bioinformatics Analysis Team, Research Core Center, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Hyeon","family":"Ye","sequence":"additional","affiliation":[{"name":"Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Won","family":"Choi","sequence":"additional","affiliation":[{"name":"Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeri","family":"Cho","sequence":"additional","affiliation":[{"name":"Diagnostic and Therapeutics Technology Branch, Division of Technology Convergence, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Choi","sequence":"additional","affiliation":[{"name":"Diagnostic and Therapeutics Technology Branch, Division of Technology Convergence, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Biostatistics Collaboration Team, Research Core Center, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongdoo","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Technology Convergence, National Cancer Center, 323 Ilsan-ro, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Gu","family":"Heo","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, MA 02215, USA"},{"name":"The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namshik","family":"Han","sequence":"additional","affiliation":[{"name":"Milner Therapeutics Institute, University of Cambridge, Cambridge CB2 0AW, UK"},{"name":"Cambridge Centre for AI in Medicine, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, UK"},{"name":"Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong-Man","family":"Hong","sequence":"additional","affiliation":[{"name":"Bioinformatics Analysis Team, Research Core Center, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"},{"name":"Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrg.2016.49","article-title":"Coming of age: Ten years of next-generation sequencing technologies","volume":"17","author":"Goodwin","year":"2016","journal-title":"Nat. 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