Evidence map›Paper›PMID 29780001›Full record

ArticleThe Lancet. Haematology2018

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

William J Lane, Connie M Westhoff, Nicholas S Gleadall, Maria Aguad, Robin Smeland-Wagman, Sunitha Vege, Daimon P Simmons, Helen H Mah, Matthew S Lebo, Klaudia Walter and 12 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Haematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01736566 (The MedSeq Project Pilot Study), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% of its field
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.

NCT01736566 nacompletednot on this map

The MedSeq Project Pilot Study: Integrating Whole Genome Sequencing Into the Practice of Clinical Medicine

TypeinterventionalSponsorBrigham and Women's HospitalRan2011 to 2021Enrolled213ConditionsHealthy Adults (Full Study and Extension Phase), Hypertrophic Cardiomyopathy or Dilated CardiomyopathyArmsFamily History + Whole Genome Sequencing, Family History Only
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
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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

22 authors at 11 institutions in 2 countries.

William J LaneDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: wlane@bwh.harvard.edu.
Connie M WesthoffNew York Blood Center, New York, NY, USA.
Nicholas S GleadallDepartment of Haematology, University of Cambridge, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge, UK.
Maria AguadDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Robin Smeland-WagmanDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Sunitha VegeNew York Blood Center, New York, NY, USA.
Daimon P SimmonsDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Helen H MahDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Matthew S LeboDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Laboratory for Molecular Medicine, Boston, MA, USA; Partners Personalized Medicine, Boston, MA, USA.
Klaudia WalterWellcome Trust Sanger Institute, Hinxton, UK.
Nicole SoranzoDepartment of Haematology, University of Cambridge, Cambridge, UK; Wellcome Trust Sanger Institute, Hinxton, UK; Cambridge Substantive Site, Health Data Research UK, Wellcome Genome Campus, Hinxton, UK.
Emanuele Di AngelantonioMedical Research Council and British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK; Cambridge Substantive Site, Health Data Research UK, Wellcome Genome Campus, Hinxton, UK.
John DaneshMedical Research Council and British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, and British Heart Foundation Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, UK; Wellcome Trust Sanger Institute, Hinxton, UK; Cambridge Substantive Site, Health Data Research UK, Wellcome Genome Campus, Hinxton, UK.
David J RobertsNational Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK; NHS Blood and Transplant-Oxford Centre, Oxford, UK; Biomedical Research Centre Haematology Theme and Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Nick A WatkinsNational Health Service (NHS) Blood and Transplant, Cambridge, UK.
Willem H OuwehandDepartment of Haematology, University of Cambridge, Cambridge, UK; Department of Public Health and Primary Care, and British Heart Foundation Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge, UK; NHS Blood and Transplant-Oxford Centre, Oxford, UK.
Adam S ButterworthMedical Research Council and British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK; Cambridge Substantive Site, Health Data Research UK, Wellcome Genome Campus, Hinxton, UK.
Richard M KaufmanDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Heidi L RehmHarvard Medical School, Boston, MA, USA; Laboratory for Molecular Medicine, Boston, MA, USA; Partners Personalized Medicine, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Boston, MA, USA.
Leslie E SilbersteinDivision of Transfusion Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Robert C GreenDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Partners Personalized Medicine, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Boston, MA, USA.
MedSeq Project
Brigham and Women's Hospital · USMass General Brigham · USUniversity of Cambridge · GBWellcome Sanger Institute · GBNew York Blood Center · USBritish Heart Foundation · GBHarvard University · USMedical Research Council · GBNational Health Service · GBNHS Blood and Transplant · GBOxford BioMedica (United Kingdom) · GB

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Transcription regulation in hematopoiesisP01HL095489 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI PARK, SHINYOUNG · 2010 to 2020
$20.1M
Trial of risk mangement for prevention of accelerated atherosclerosis in SLEP60AR047782 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KATZ, JEFFREY NEIL · 2001 to 2016
$18.8M
Finding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6M
VASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7M
Integration of Whole Genome Sequencing into Clinical MedicineU01HG006500 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI GREEN, ROBERT C. · 2012 to 2016
$11.5M
Genome Sequence-Based Screening for Childhood Risk and Newborn IllnessU19HD077671 · NICHD · BRIGHAM AND WOMEN'S HOSPITAL · PI BEGGS, ALAN H., GREEN, ROBERT C. · 2013 to 2018
$6.1M
Impact of Disclosing Amyloid Imaging Results to Cognitively Normal IndividualsRF1AG047866 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI GREEN, ROBERT C., KARLAWISH, JASON H · 2015 to 2019
$6.0M
Disclosing Genomic Incidental Findings in a Cancer Biobank: An ELSI ExperimentR01CA154517 · NCI · MAYO CLINIC ROCHESTER · PI KOENIG, BARBARA A., PETERSEN, GLORIA M. · 2011 to 2015
$2.7M
Developing a Genomics Literacy MeasureR03HG008809 · NHGRI · MIDDLEBURY COLLEGE · PI LINDERMAN, MICHAEL DAVID · 2016 to 2017
$128k
British Heart Foundation RG/13/13/30194Medical Research Council MR/L003120/1NCI NIH HHS R01 CA154517NHGRI NIH HHS R03 HG008809NHGRI NIH HHS U01 HG006500NHGRI NIH HHS U01 HG008685NHLBI NIH HHS P01 HL095489NHLBI NIH HHS T32 HL007627NIAMS NIH HHS P60 AR047782NIA NIH HHS RF1 AG047866NIA NIH HHS U01 AG024904NICHD NIH HHS U19 HD077671Wellcome Trust
6 · The paper itself

Abstract

backgroundThere are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens.

methodsThis whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.

findingsWe iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).

interpretationBy enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.

fundingNational Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

Indexed as

Whole Genome SequencingABO Blood-Group SystemAdolescentAdultAgedAged, 80 and overAlgorithmsAntigens, Human PlateletBlood Grouping and CrossmatchingBlood PlateletsDatabases, GeneticErythrocytesGenome, HumanHumansMiddle AgedRandomized Controlled Trials as TopicABO Blood-Group SystemAntigens, Human PlateletRHCE protein, humanRh-Hr Blood-Group System

Identifiers

PMID29780001
PMCPMC6438177
OpenAlexW2804763771

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Registered trials

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.