机构：[1]Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA[2]Immuneering Corporation, One Broadway, 14th Floor, Cambridge, MA 02142, USA[3]Agilent Technologies, 11011 N Torrey Pines Rd, La Jolla, CA 92037, USA[4]Department of Information Science, University of Arkansas at Little Rock, 2801 S.Univ.Ave, Little Rock, AR 72204, USA[5]State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Hospital/Cancer Institute, Fudan University,Shanghai 200438, China[6]Agilent Technologies, 5301 Stevens Creek Blvd, Santa Clara, CA 95051, USA[7]Research and Development, Burning Rock Biotech, Shanghai 201114, China[8]Bioinformatics, Integrated DNA Technologies, Inc,1710 Commercial Park, Coralville, IA 52241, USA[9]iGeneTech, 8 Shengmingyuan Rd, Zhongguancun Life Science Park,Changping District, Beijing 100080, China[10]Illumina Inc,5200 Illumina Way, San Diego, CA 92122, USA[11]Research and Development, QIAGEN Sciences Inc , Frederick, MD 21703, USA[12]Market & Application Development Bioinformatics,Roche Sequencing Solutions Inc, 4300 Hacienda Dr, Pleasanton, CA 94588, USA[13]Thermo Fisher Scientific, 110 Miller Ave, Ann Arbor, MI 48104, USA[14]Clinical Diagnostic Division, Thermo Fisher Scientific, 46500 Kato Rd, Fremont, CA 94538, USA[15]Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 W Markham St,Little Rock, AR 72205, USA[16]Departments of Medicine, Pathology, and Cancer Biology, College of Medicine and Life Sciences, University of Toledo Health Sciences Campus, 3000 Arlington Ave, Toledo, OH 43614, USA[17]National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA[18]Department of Immunology,Genomics and Microarray Core Facility, University of Texas Southwestern Medical Center, 5323 Harry Hine Blvd, Dallas,TX 75390, USA[19]Research and Development, Roche Sequencing Solutions Inc , 500 South Rosa Rd, Madison, WI 53719,USA[20]Clinical Sequencing Division, Thermo Fisher Scientific, 180 Oyster Point Blvd, South San Francisco, CA 94080,USA[21]Marketing, Integrated DNA Technologies, Inc , 1710 Commercial Park, Coralville, IA 52241, USA[22]Icahn Instituteand Dept.of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York,NY 10029, USA[23]Greenwood Genetic Center, 106 Gregor Mendel Circle, Greenwood, SC 29646, USA[24]Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China[25]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China[26]Institute of Pathology, FudanUniversity, Shanghai 200032, China[27]JMP Life Sciences, SAS Institute Inc, Cary, NC 27519, USA[28]Departments of Pathology and Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84108, USA[29]R&D Genomics MPS,Institute for Clinical and Experimental Pathology ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA[30]ResearchDx, Inc , 5 Mason, Irvine, CA 92618, USA[31]Department of Computer Science, Engineering and Physics, University of Michigan-Flint, Flint, MI 48502, USA[32]Garvan Institute of Medical Research, Sydney, NSW, Australia[33]StVincent’s Clinical School, University of New South Wales, Sydney, NSW 2010, Australia[34]Department of Pathology,College of Medicine and Life Sciences, The University of Toledo, Toledo, OH 43614, USA[35]Lucas County Coroner’s Office, 2595 Arlington Ave , Toledo, OH 43614, USA[36]Division of Gastroenterology and Hepatology, Mayo Clinic,Rochester, MN 55905, USA[37]OmniSeq, Inc.700 Ellicott St, Buffalo, NY 14203, USA[38]Department of Physiology and Biophysics, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA[39]Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA[40]Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA[41]Fondazione Bruno Kessler,38123 Trento, Italy[42]Department of Medicine, College of Medicine and Life Sciences, The University of Toledo, Toledo,OH 43614, USA[43]Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, CIBERER Instituto de Salud Carlos III, 28046 Madrid, Spain[44]EATRIS ERIC- European Infrastructure for Translational Medicine, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands[45]Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia[46]St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia[47]Cancer Genetics Inc, 201 Route 17 N, Meadows Office Building, Rutherford, NJ 07070,USA[48]Institute for Personalized Cancer Therapy, MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA[49]Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China[50]HK3 Lab, Milan, Italy[51]Molecular Laboratory, Prof.F.Raue, Im Weiher 12, Heidelberg,Germany[52]Agilent Technologies, 1834 State Hwy 71 West, Cedar Creek, TX 78612, USA[53]Department of Pathology,Strata Oncology, Inc, Ann Arbor, MI 48103, USA[54]Human Genome Sequencing Center, Baylor College of Medicine, 1Baylor Plaza, Houston, TX 77030, USA[55]Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114,USA[56]NGS Products and Services, Integrated DNA Technologies, Inc, 1710 Commercial Park, Coralville, IA 52241, USA[57]Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, 800 Commissioners Rd E, London, Ontario N6A5W9, Canada[58]Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester,MN 55905, USA[59]Bioinformatics Research, Institute of Molecular Biotechnology, Boku University Vienna, Vienna, Austria[60]Małopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland[61]Department of Biotechnology,Boku University, Vienna, Austria[62]Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz,IdiPaz, CIBERER Instituto de Salud Carlos III, 28046 Madrid, Spain[63]ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, European Commission, Lille, France[64]Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, No.17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China[65]Center of Genome and Personalized Medicine, Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, Liaoning, China[66]Geneis, 5 Guangshun North St, Chaoyang District, Beijing 100102, China[67]GeneSmile Ltd Co, Jiangsu Cancer Hospital, 42 Baiziting St, Xuanwu District, Nanjing 210009, Jiangsu, China[68]Genycell Biotech España, Calle Garrido Atienza, 18320 Santa Fe, Granada, Spain[69]CMINDS Research Center, Department of Electrical and Computer Engineering, College of Engineering, University of Massachusetts Lowell, Lowell, MA 01854, USA[70]Department of Genetics, University of North Carolina, 250 Bell Tower Drive, Chapel Hill, NC 27599, USA[71]Accugenomics, Inc, 1410 Commonwealth Drive, Suite 105, Wilmington, NC 20403, USA[72]Translational Research Laboratory, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Ave, Boston, MA 02215, USA[73]Bioinformatics and Computational Biology Laboratory, National Heart Lung and Blood Institute, National Institutes of Health,Bethesda, MD 20892, USA[74]Astrazeneca Pharmaceuticals, 35 Gatehouse Dr, Waltham, MA 02451, USA[75]Department of Pathology and Laboratory Medicine, Western University, London, Ontario N6A3K7, Canada[76]Institute for Molecular Medicine Finland (FIMM), Nordic EMBL Partnership for Molecular Medicine, HiLIFE Unit, Biomedicum Helsinki 2U (D302b), P.O.Box 20, (Tukholmankatu 8), FI-00014 University of Helsinki, Helsinki, Finland[77]Laboratory for Molecular Genetics, Endocrine Practice, Im Weiher 12, 69121 Heidelberg, Germany[78]Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA[79]Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University,500 Dongchuan Rd, Shanghai 200241, China[80]National Centre for Cardiovascular Research (CNIC), Madrid, Spain[81]Primbio Genes Biotechnology, Building C6-501, Biolake, No.666 Gaoxin Ave , East Lake High-tech Development Zone,Wuhan 430074, Hubei, China[82]National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA[83]Center of Molecular Medicine, Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic[84]Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA[85]Division of Microbiology & Molecular Genetics,Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA[86]Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ 85259, USA[87]Department of Health Sciences, Mayo Clinic,Scottsdale, AZ 85259, USA[88]Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic,Scottsdale, AZ 85259, USA[89]College of Chemistry, Sichuan University, Chengdu 610064, Sichuan, China[90]Science forLife Laboratory, Karolinska Institutet, Tomtebodavägen 23B, 171 65 Solna, Sweden[91]National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 45 Center Drive, Bethesda, MD 20894, USA[92]Department of Biostatistics, Columbia Mailman School of Public Health, 722 West 168th St , New York, NY 10032,USA[93]Center for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China[94]Clinical Laboratory, Burning Rock Biotech, Guangzhou 510300, Guangdong, China[95]Geneplus, PKUCare Industrial Park, Changping District, Beijing 102206, China[96]Australian Institute of Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD, Australia[97]Genomics and Epigenetics Theme, Garvan Institute of Medical Research,Sydney, NSW, Australia[98]Human Phenome Institute, Fudan University, Shanghai 201203, China[99]Fudan-Gospel Joint Research Center for Precision Medicine, Fudan University, Shanghai 200438, China[100]Q2 Solutions - EA Genomics,5927 S Miami Blvd, Morrisville, NC 27560, USA
Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing.
All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5-20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden.
This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.
基金：
Leming Shi and Yuanting
Zheng were supported by the National Key R&D Project of China (2018YFE0201600), the National Natural Science
Foundation of China (31720103909), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01).Donald J. Johann, Jr. acknowledges the support by FDA BAA grant HHSF223201510172C. Timothy Mercer and Ira
Deveson were supported by the National Health and Medical Research Council (NHMRC) of Australia grants
APP1108254, APP1114016, and APP1173594 and Cancer Institute NSW Early Career Fellowship 2018/ECF013. This research has also been, in part, financially supported by the MEYS of the CR under the project CEITEC 2020 (LQ1601), by
MH CR, grant No. (NV19-03-00091). Part of this work was carried out with the support of research infrastructure EATR
IS-CZ, ID number LM2015064, funded by MEYS CR. Boris Tichy and Nikola Tom were supported by research infrastructure EATRIS-CZ, ID number LM2018133 funded by MEYS CR and MEYS CR project CEITEC 2020 (LQ1601).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|1 区生物学
小类|1 区生物工程与应用微生物1 区遗传学
最新[2023]版：
大类|1 区生物学
小类|1 区生物工程与应用微生物1 区遗传学
第一作者：
第一作者机构：[1]Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA
共同第一作者：
通讯作者：
通讯机构：[5]State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Hospital/Cancer Institute, Fudan University,Shanghai 200438, China[98]Human Phenome Institute, Fudan University, Shanghai 201203, China[99]Fudan-Gospel Joint Research Center for Precision Medicine, Fudan University, Shanghai 200438, China
推荐引用方式(GB/T 7714)：
Binsheng Gong,Dan Li,Rebecca Kusko,et al.Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.[J].Genome biology.2021,22(1):109.doi:10.1186/s13059-021-02315-0.
APA：
Binsheng Gong,Dan Li,Rebecca Kusko,Natalia Novoradovskaya,Yifan Zhang...&Joshua Xu.(2021).Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions..Genome biology,22,(1)
MLA：
Binsheng Gong,et al."Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.".Genome biology 22..1(2021):109
生物学