ArticleNature genetics2015
Factors influencing success of clinical genome sequencing across a broad spectrum of disorders.
3 registry-linked trialsAbstract read
In one paragraph
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 213 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
213citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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.
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.
Investigating the Feasibility and Implementation of Whole Genome Sequencing in Patients With Suspected Genetic Disorder
Whole Exome Sequencing and Whole Genome Sequencing for Nonimmune Fetal/Neonatal Hydrops
Emergency PanorOmic Wide Association Study in Respiratory Infectious Disease (ePWAS-RID)
Who cites it
213 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment.Archives of public health = Archives belges de sante publique · 2023Pooled it
- Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Pooled it
- Association between XRCC3 Thr241Met polymorphism and nasopharyngeal carcinoma risk: evidence from a large-scale case-control study and a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Pooled it
- A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants.American journal of human genetics · 2019Trial
- dicast: a machine learning method for accurate structural variant detection from short-read sequencing data.Genome biology · 2026Article
- RankVar: machine learning-based variant ranking and reinterpretation for rare genetic diseases.Genome medicine · 2026Article
- [Guideline development for MRD diagnostics in AML as a blueprint for solid tumors].Pathologie (Heidelberg, Germany) · 2026Review
- Historical Perspectives, Classification and Diagnostic Approaches of Inborn Errors of Metabolism: A Systematic Review and Meta-Analysis.Metabolites · 2026Review
- Autosomal Dominant Erythrocytosis Caused by Non-Renal Erythropoietin (EPO) Due to EPO c.-136 G>A Germline Mutation.American journal of hematology · 2026Article
- Applying National Whole-genome Sequencing Findings for Rare Diseases in Clinical Practice: The Imperative of a Multidisciplinary Approach.Annals of laboratory medicine · 2026Article
- Genomics of pregnancy loss.Journal of assisted reproduction and genetics · 2026Review
- A feasibility study of whole genome germline testing as an adjunct screening tool in a UK general private practice.Scientific reports · 2025Article
- GREGoR: accelerating genomics for rare diseases.Nature · 2025Article
- Analytical Validation of a Genomic Newborn Screening Workflow.International journal of neonatal screening · 2025Article
- NGS Approaches in Clinical Diagnostics: From Workflow to Disease-Specific Applications.International journal of molecular sciences · 2025Review
- A systematic analysis of contemporary whole exome sequencing capture kits to optimise high-coverage capture of CCDS regions.NAR genomics and bioinformatics · 2025Article
- Clinical implementation of a multidisciplinary pipeline for genome sequencing in rare diseases: A prospective, multicenter, observational cohort study.Clinical and translational medicine · 2025Article
- Blood RNA-seq in rare disease diagnostics: a comparative study of cases with and without candidate variants.Journal of translational medicine · 2025Article
- Non-syndromic craniosynostosis.Nature reviews. Disease primers · 2025Review
- Mainstreaming genomics in the National Health Service in England: a survey to understand preparedness and confidence among paediatricians.BMJ paediatrics open · 2025Article
153 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
110 authors.
Jenny C Taylor *NIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Hilary C Martin *Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Stefano LiseWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
John BroxholmeWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Jean-Baptiste CazierWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Andy RimmerWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Alexander KanapinWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Gerton LunterWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Simon FiddyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Chris AllanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
A Radu AricescuWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Moustafa AttarWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Christian BabbsMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Jennifer BecqIllumina Cambridge Limited, Saffron Walden, UK.
David BeesonNeurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Celeste BentoHematology Department, Centro Hospitalar e Universitário de Coimbra, Portugal.
Patricia BignellMolecular Haematology Department, Oxford University Hospitals NHS Trust, Oxford, UK.
Edward BlairDepartment of Clinical Genetics, Oxford University Hospitals NHS Trust, Oxford, UK.
Veronica J BuckleMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Katherine BullWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Ondrej CaisNeurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
Holger CarioDepartment of Pediatrics and Adolescent Medicine, University Medical Center, Ulm, Germany.
Helen ChapelPrimary Immunodeficiency Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Richard R CopleyNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Richard CornallCentre for Cellular and Molecular Physiology, University of Oxford, Oxford, UK.
Jude CraftNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Karin DahanCentre de Génétique Humaine, Institut de Génétique et de Pathologie, Gosselies, Belgium.
Emma E DavenportWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Calliope DendrouMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Olivier DevuystInstitute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Aimée L FenwickClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Jonathan FlintWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Lars FuggerMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Rodney D GilbertUniversity Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, UK.
Anne GorielyClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Angie GreenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Ingo H GregerNeurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
Russell GrocockIllumina Cambridge Limited, Saffron Walden, UK.
Anja V GruszczykClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Robert HastingsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Edouard HattonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Doug HiggsMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Adrian HillWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Chris HolmesWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Malcolm HowardNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Linda HughesWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Peter HumburgWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
David JohnsonCraniofacial Unit, Department of Plastic and Reconstructive Surgery, Oxford University Hospitals NHS Trust, Oxford, UK.
Fredrik KarpeOxford Laboratory for Integrative Physiology, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Zoya KingsburyIllumina Cambridge Limited, Saffron Walden, UK.
Usha KiniDepartment of Clinical Genetics, Oxford University Hospitals NHS Trust, Oxford, UK.
Julian C KnightWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Jonathan KrohnWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Sarah LambleWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Craig LangmanKidney Diseases, Feinberg School of Medicine, Northwestern University and the Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Lorne LonieWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Joshua LuckClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Davis McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Simon J McGowanClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Mary Frances McMullinCentre for Cancer Research and Cell Biology, Queen's University, Belfast, UK.
Kerry A MillerClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Lisa MurrayIllumina Cambridge Limited, Saffron Walden, UK.
Andrea H NémethNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
M Andrew NesbitAcademic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
David NuttCentre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College, London, UK.
Elizabeth OrmondroydDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Annette Bang OturaiDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
Alistair PagnamentaNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Smita Y PatelPrimary Immunodeficiency Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Melanie PercyDepartment of Haematology, Belfast City Hospital, Belfast, UK.
Nayia PetousiNuffield Department of Medicine, University of Oxford, Oxford, UK.
Paolo PiazzaWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Sian E PiretAcademic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Guadalupe Polanco-EcheverryWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Niko PopitschNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Fiona PowrieTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Chris PughNuffield Department of Medicine, University of Oxford, Oxford, UK.
Lynn QuekMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Peter A RobbinsDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Kathryn RobsonMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Alexandra RussoDepartment of Pediatrics, University Hospital, Mainz, Germany.
Natasha SahgalWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Pauline A van SchouwenburgPrimary Immunodeficiency Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Anna SchuhNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Earl SilvermanDivision of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Alison SimmonsMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Per Soelberg SørensenDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
Elizabeth SweeneyDepartment of Clinical Genetics, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
John TaylorNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Rajesh V ThakkerAcademic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Ian TomlinsonNIHR Comprehensive Biomedical Research Centre, Oxford, UK.
Amy TrebesWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Stephen Rf TwiggClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Holm H UhligTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Paresh VyasMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Tim VyseDivision of Genetics, King's College London, Guy's Hospital, London, UK.
Steven A WallCraniofacial Unit, Department of Plastic and Reconstructive Surgery, Oxford University Hospitals NHS Trust, Oxford, UK.
Hugh WatkinsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Michael P WhyteCenter for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St Louis, Missouri, USA.
Lorna WittyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Ben WrightWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Chris YauWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
David BuckWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Sean HumphrayIllumina Cambridge Limited, Saffron Walden, UK.
Peter J RatcliffeNuffield Department of Medicine, University of Oxford, Oxford, UK.
John I BellOffice of the Regius Professor of Medicine, University of Oxford, Oxford, UK.
Andrew Om WilkieClinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
David BentleyIllumina Cambridge Limited, Saffron Walden, UK.
Peter DonnellyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Gilean McVeanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Funding
Biotechnology and Biological Sciences Research Council BB/I02593X/1British Heart Foundation RG/12/16/29939Cancer Research UK 16459Department of Health NIHR-RP-R3-12-026European Research Council 281824Medical Research Council G0900747Medical Research Council G0900747 91070Medical Research Council G1000467Medical Research Council G1000801Medical Research Council G9825289Medical Research Council L009609Medical Research Council MC_U105174197Medical Research Council MC_U137961145Medical Research Council MC_UC_12010/3Medical Research Council MC_UP_1502/3Medical Research Council MC_UU_12009/1Medical Research Council MC_UU_12009/11Medical Research Council MC_UU_12010/3Medical Research Council MC_UU_12010/6Medical Research Council MC_UU_12010/7Medical Research Council MR/L001411/1Medical Research Council MR/L009609/1Medical Research Council MR/M006824/1Wellcome Trust 090532Wellcome Trust 090532/Z/09/ZWellcome Trust 091182Wellcome Trust 093329Wellcome Trust 095552Wellcome Trust 095688Wellcome Trust 100308Wellcome Trust 102731Wellcome Trust 102731/Z/13/Z
Abstract
To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.
Indexed as
High-Throughput Nucleotide SequencingMolecular Diagnostic TechniquesBase SequenceDNA Mutational AnalysisGenetic Diseases, InbornGenome, HumanHumansMolecular Sequence AnnotationPolymorphism, Single NucleotideSensitivity and Specificity
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