ArticleNature biotechnology2021
Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing.
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Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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112citing papers in PubMed
17.4field-weighted citation impact, top 1% of its field
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Who cites it
112 citing papers in PubMed, 200 citations in OpenAlex.
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- VariantMedium: sensitive and generalizable somatic point mutation calling with 3D DenseNets trained and evaluated on experimental data.Genome medicine · 2026Article
- Benchmarking Q40 sequencing for sensitive and efficient detection of rare genomic variants.Genome biology · 2026Article
- Navigating luminal heterogeneity: etiology-based proteogenomic subtyping for targeted treatment strategies in breast cancer.Molecular cancer · 2026Article
- Immune checkpoint inhibitor resistance in dMMR high-grade intraepithelial neoplasia with lynch syndrome-associated colon cancer: a case report.BMC gastroenterology · 2026Article
- Subtyping atypical eosinophilic renal cell tumours through integrated morphological, immunohistochemical, and mutational characters.BMC cancer · 2026Article
- Database of recurrent mutations, an unbiased web resource to browse recurrent mutations in cancers.iScience · 2026Article
- High-Grade Serous Ovarian Carcinoma in the Genomics Era: Current Applications, Challenges and Future Directions.International journal of molecular sciences · 2026Review
- Epigenomic, transcriptomic, and proteomic characterization of breast cancer cell line reference samples.Cell reports methods · 2026Article
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- Comprehensive genomic profiling of neuroendocrine neoplasms of the colorectum.Frontiers in genetics · 2026Article
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- Comprehensive benchmarking of methods for mutation calling in circulating tumor DNA.Nature communications · 2025Article
- Benchmarking Ploidy Estimation Methods for Bulk and Single-Cell Whole Genome Sequencing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evaluation of false positive and false negative errors in targeted next generation sequencing.Genome biology · 2025Article
- Enabling whole genome sequencing analysis from FFPE specimens in clinical oncology.Nature communications · 2025Article
- Comparative Evaluation of Mutect2, Strelka2, and FreeBayes for Somatic SNV Detection in Synthetic and Clinical Whole-Exome Sequencing Data.Biomolecules · 2025Article
- Comprehensive benchmarking of somatic mutation detection by the SMaHT Network.bioRxiv : the preprint server for biology · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
90 authors at 20 institutions in 11 countries.
Wenming Xiao *The Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA. wenming.xiao@fda.hhs.gov.ORCID http://orcid.org/0000-0003-4096-9724
Luyao Ren *State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
Zhong ChenCenter for Genomics, Loma Linda University School of Medicine, Loma Linda, CA, USA.ORCID http://orcid.org/0000-0003-2444-8216
Li Tai FangBioinformatics Research & Early Development, Roche Sequencing Solutions Inc., Belmont, CA, USA.ORCID http://orcid.org/0000-0003-3201-5162
Yongmei ZhaoAdvanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID http://orcid.org/0000-0003-0800-4658
Justin LackAdvanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Meijian GuanSAS Institute Inc., Cary, NC, USA.
Bin ZhuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-0172-5516
Erich JaegerIllumina Inc., Foster City, CA, USA.
Liz KerriganATCC, Manassas, VA, USA.
Thomas M BlomquistDepartments of Medicine and Pathology, University of Toledo Medical Center, Toledo, OH, USA.
Tiffany HungGenentech, South San Francisco, CA, USA.
Marc SultanBiomarker Development, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Kenneth IdlerComputational Genomics, Genomics Research Center, AbbVie, North Chicago, IL, USA.
Charles LuComputational Genomics, Genomics Research Center, AbbVie, North Chicago, IL, USA.
Andreas SchererInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-4254-7122
Rebecca KuskoImmuneering Corporation, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6730-5990
Malcolm MoosThe Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Chunlin XiaoNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8702-4889
Stephen T SherryNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Ogan D AbaanIllumina Inc., Foster City, CA, USA.
Wanqiu ChenCenter for Genomics, Loma Linda University School of Medicine, Loma Linda, CA, USA.ORCID http://orcid.org/0000-0003-3706-7834
Xin ChenCenter for Genomics, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Jessica NordlundEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.
Ulrika LiljedahlEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.
Roberta MaestroEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-6642-5592
Maurizio PolanoEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.
Jiri DrabekEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.
Petr VojtaEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-0036-1853
Sulev KõksEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-6087-6643
Ene ReimannEuropean Infrastructure for Translational Medicine, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0002-5410-4433
Bindu Swapna MadalaGarvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Timothy MercerGarvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0001-8780-894X
Chris MillerComputational Genomics, Genomics Research Center, AbbVie, North Chicago, IL, USA.
Howard JacobComputational Genomics, Genomics Research Center, AbbVie, North Chicago, IL, USA.
Tiffany TruongIllumina Inc., Foster City, CA, USA.
Ali MoshrefiIllumina Inc., Foster City, CA, USA.
Aparna NatarajanIllumina Inc., Foster City, CA, USA.
Ana GranatIllumina Inc., Foster City, CA, USA.
Gary P SchrothIllumina Inc., Foster City, CA, USA.ORCID http://orcid.org/0000-0002-3055-056X
Rasika KalameghamGenentech, South San Francisco, CA, USA.
Eric PetersGenentech, South San Francisco, CA, USA.
Virginie PetitjeanBiomarker Development, Novartis Institutes for Biomedical Research, Basel, Switzerland.
Ashley WaltonAdvanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Tsai-Wei ShenAdvanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID http://orcid.org/0000-0001-9644-1748
Keyur TalsaniaAdvanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Cristobal Juan VeraAdvanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Kurt LangenbachATCC, Manassas, VA, USA.
Maryellen de MarsATCC, Manassas, VA, USA.
Jennifer A HippDepartments of Medicine and Pathology, University of Toledo Medical Center, Toledo, OH, USA.
James C WilleyDepartments of Medicine and Pathology, University of Toledo Medical Center, Toledo, OH, USA.
Jing WangNational Institute of Metrology, Beijing, China.
Jyoti ShettySequencing Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Yuliya KrigaSequencing Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Arati RaziuddinSequencing Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID http://orcid.org/0000-0001-9361-8691
Bao TranSequencing Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Yuanting ZhengState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
Ying YuState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
Margaret CamCCR Collaborative Bioinformatics Resource, Office of Science and Technology Resources, Center for Cancer Research, Bethesda, MD, USA.
Parthav JailwalaCCR Collaborative Bioinformatics Resource, Office of Science and Technology Resources, Center for Cancer Research, Bethesda, MD, USA.
Cu NguyenComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
Daoud MeerzamanComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
Qingrong ChenComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
Chunhua YanComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
Ben ErnestDigicon, McLean, VA, USA.
Urvashi MehraDigicon, McLean, VA, USA.
Roderick V JensenDepartment of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Wendell JonesQ2 Solutions-EA Genomics, Morrisville, NC, USA.ORCID http://orcid.org/0000-0002-9676-5387
Jian-Liang LiIntegrative Bioinformatics, National Institute of Environmental Health Sciences, Durham, NC, USA.ORCID http://orcid.org/0000-0002-6487-081X
Brian N PapasIntegrative Bioinformatics, National Institute of Environmental Health Sciences, Durham, NC, USA.
Mehdi PiroozniaBioinformatics and Computational Biology Core, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4210-6458
Yun-Ching ChenBioinformatics and Computational Biology Core, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Fayaz SeifuddinBioinformatics and Computational Biology Core, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3357-7888
Zhipan LiSentieon Inc., Mountain View, CA, USA.
Xuelu LiuCenter for Information Technology, National Institutes of Health, Bethesda, MD, USA.
Wolfgang ReschCenter for Information Technology, National Institutes of Health, Bethesda, MD, USA.
Jingya WangAstraZeneca, Gaithersburg, MD, USA.
Leihong WuNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Gokhan YavasNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Corey MilesNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Baitang NingNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Weida TongNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
Christopher E MasonDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-1850-1642
Eric DonaldsonThe Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Samir LababidiOffice of the Chief Scientist, Office of the Commissioner, US Food and Drug Information, Silver Spring, MD, USA.
Louis M StaudtLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Zivana TezakThe Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA.
Huixiao HongNational Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.ORCID http://orcid.org/0000-0001-8087-3968
Charles WangCenter for Genomics, Loma Linda University School of Medicine, Loma Linda, CA, USA. oxwang@gmail.com.ORCID http://orcid.org/0000-0001-8861-2121
Leming ShiState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China. lemingshi@fudan.edu.cn.ORCID http://orcid.org/0000-0002-2981-4150
Frederick National Laboratory for Cancer Research · USNational Institutes of Health · USIllumina (United States) · USNational Center for Toxicological Research · USAbbVie (United States) · USFudan University · CNLoma Linda University · USNational Cancer Institute · USUnited States Food and Drug Administration · USAmerican Type Culture Collection · USCenter for Translational Molecular Medicine · NLCentro di Riferimento Oncologico · ITUniversity of Toledo Medical Center · USAstraZeneca (United States) · USGarvan Institute of Medical Research · AUNational Institute of Environmental Health Sciences · USNovartis (Switzerland) · CHOffice of Science · USCenter for Biologics Evaluation and Research · USCornell University · US
Funding
High Throughput DNA SequencerS10OD019960 · OD · LOMA LINDA UNIVERSITY · PI WANG, CHARLES · 2015 to 2015
$272kIntramural NIH HHS Z99 CA999999NCI NIH HHS HHSN261201400008CNCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INIH HHS 75N910D00024NIH HHS S10 OD019960U.S. Department of Health & Human Services | National Institutes of Health (NIH) S10OD019960
Abstract
Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
Indexed as
BenchmarkingCell LineCell Line, TumorExome SequencingHigh-Throughput Nucleotide SequencingHumansMutationNeoplasmsReproducibility of ResultsSequence Analysis, DNAWhole Genome Sequencing
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