Evidence map›Paper›PMID 34980216›Full record

ArticleGenome biology2022

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing.

Bohu Pan, Luyao Ren, Vitor Onuchic, Meijian Guan, Rebecca Kusko, Steve Bruinsma, Len Trigg, Andreas Scherer, Baitang Ning, Chaoyang Zhang and 45 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed.

  1. Article
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  6. Review
  7. Long-read sequencing reveals genomic and epigenomic variation in the dark genome of human Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

55 authors.

Bohu Pan *Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Luyao Ren *State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China.
Vitor Onuchic *Illumina Inc., San Diego, CA, 92122, USA.
Meijian Guan *SAS Institute Inc., Cary, NC, 27513, USA.
Rebecca Kusko *Immuneering Corporation, Cambridge, MA, 02142, USA.
Steve BruinsmaIllumina Inc., San Diego, CA, 92122, USA.
Len TriggReal Time Genomics, Hamilton, New Zealand.
Andreas SchererInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Baitang NingDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Chaoyang ZhangSchool of Computing Sciences and Computer Engineering, University of Southern Mississippi, Hattiesburg, MS, 39406, USA.
Christine Glidewell-KenneyIllumina Inc., San Diego, CA, 92122, USA.
Chunlin XiaoNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
Eric DonaldsonCenter for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Fritz J SedlazeckHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Gary SchrothIllumina Inc., San Diego, CA, 92122, USA.
Gokhan YavasDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Haiying GrunenwaldIllumina Inc., San Diego, CA, 92122, USA.
Haodong ChenSentieon Inc., San Jose, CA, 95134, USA.
Heather MeinholzIllumina Inc., San Diego, CA, 92122, USA.
Joe MeehanDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Jing WangCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, 100013, China.
Jingcheng YangState Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China.
Jonathan FooxDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10021, USA.
Jun ShangState Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China.
Kelci MiclausSAS Institute Inc., Cary, NC, 27513, USA.
Lianhua DongCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, 100013, China.
Leming ShiState Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China.
Marghoob MohiyuddinRoche Sequencing Solutions, Santa Clara, CA, 95050, USA.
Mehdi PiroozniaBioinformatics and Computational Biology Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Ping GongEnvironmental Laboratory, U.S. Army Engineer Research and Development Center, Vicksburg, MS, 39180, USA.
Rooz GolshaniIllumina Inc., San Diego, CA, 92122, USA.
Russ WolfingerSAS Institute Inc., Cary, NC, 27513, USA.
Samir LababidiOffice of Health Informatics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, 20993, USA.
Sayed Mohammad Ebrahim SahraeianRoche Sequencing Solutions, Santa Clara, CA, 95050, USA.
Steve SherryNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
Tao HanDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Tao ChenDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Tieliu ShiThe Center for Bioinformatics and Computational Biology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Wanwan HouState Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China.
Weigong GeDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Wen ZouDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Wenjing GuoDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Wenjun BaoSAS Institute Inc., Cary, NC, 27513, USA.
Wenzhong XiaoStanford Genome Technology Center, Stanford University School of Medicine, Palo Alto, CA, 94305, USA.
Xiaohui FanPharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Yoichi GondoDepartment of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Ying YuState Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China.
Yongmei ZhaoCCR-SF Bioinformatics Group, Advanced Biomedical and Computational Sciences, Biomedical Informatics and Data Science, Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA.
Zhenqiang SuTakeda Pharmaceuticals, Cambridge, MA, 02139, USA.
Zhichao LiuDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Weida TongDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
Wenming XiaoDivision of Molecular Genetics and Pathology, Center for Device and Radiological Health, US Food and Drug Administration, Silver Spring, MD, 20993, USA.
Justin M ZookMaterial Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA. justin.zook@nist.gov.
Yuanting ZhengState Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, 200438, China. zhengyuanting@fudan.edu.cn.
Huixiao HongDivision of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA. huixiao.hong@fda.hhs.gov.ORCID 0000-0001-8087-3968

Funding

National Biomedical Information ServicesZIHLM200888 · NLM · NATIONAL LIBRARY OF MEDICINE · PI PALTOO, DINA · 2009 to 2025
$5200.7M
Genomic Architecture of Common Disease in Diverse Populations: WGS of Ongoing Hemorrhagic Stroke Study SupplementUM1HG008898 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2016 to 2020
$77.0M
NHGRI NIH HHS UM1 HG008898
6 · The paper itself

Abstract

backgroundReproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS.

resultsTo dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×.

conclusionsOur findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

Indexed as

Genome, HumanPolymorphism, Single NucleotideHigh-Throughput Nucleotide SequencingHumansINDEL MutationReproducibility of ResultsWhole Genome Sequencing

Identifiers

PMID34980216
PMCPMC8722114

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.