Evidence map›Paper›PMID 34780721›Full record

ArticleGastroenterology2022

An Integrated Taxonomy for Monogenic Inflammatory Bowel Disease.

Chrissy Bolton, Christopher S Smillie, Sumeet Pandey, Rasa Elmentaite, Gabrielle Wei, Carmen Argmann, Dominik Aschenbrenner, Kylie R James, Dermot P B McGovern, Marina Macchi and 26 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 4 pooled it
9.7field-weighted citation impact, top 1% 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.

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

64 citing papers in PubMed, 4 syntheses or guidelines pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. GPR15-guided CD8Nature · 2026
    Article
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  10. The roles and heterogeneity of CD8International journal of molecular medicine · 2026
    Review
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors at 17 institutions in 7 countries.

Chrissy BoltonTranslational Gastroenterology Unit, University of Oxford, Oxford, UK; Institute of Child Health, University College London, London, UK.
Christopher S SmillieKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Sumeet PandeyTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Rasa ElmentaiteWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Gabrielle WeiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Carmen ArgmannDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Dominik AschenbrennerTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Kylie R JamesWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, Australia.
Dermot P B McGovernF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Marina MacchiTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Judy ChoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Dror S ShouvalInstitute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah-Tiqva, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Jochen KammermeierGastroenterology Department, Evelina London Children's Hospital, London, UK.
Sibylle KoletzkoDr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany; Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.
Krithika BagalopalTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Melania CapitaniTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Athena CavounidisTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
Elisabete PiresChemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, UK.
Carl WeidingerCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health Department of Gastroenterology, Rheumatology and Infectious Disease, Campus Benjamin Franklin, Berlin, Germany.
James McCullaghChemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, UK.
Peter D ArkwrightLydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.
Wolfram HallerDepartment of Gastroenterology and Nutrition, Birmingham Children's Hospital, Birmingham, UK.
Britta SiegmundCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health Department of Gastroenterology, Rheumatology and Infectious Disease, Campus Benjamin Franklin, Berlin, Germany.
Lauren PetersDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Luke JostinsThe Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Simon P L TravisTranslational Gastroenterology Unit, University of Oxford, Oxford, UK; Biomedical Research Center, University of Oxford, Oxford, UK.
Carl A AndersonWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Scott SnapperDivision of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA.
Christoph KleinDr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany.
Eric SchadtDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Matthias ZilbauerDepartment of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrooke's Hospital, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.
Ramnik XavierKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Sarah TeichmannWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Theory of Condensed Matter, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EBI), Wellcome Genome Campus, Hinxton UK.
Aleixo M MuiseGastroenterology Division, The Hospital for Sick Children, Toronto, Ontario, Canada; SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics and Biochemistry, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Holm H UhligTranslational Gastroenterology Unit, University of Oxford, Oxford, UK; The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, United Kingdom. Electronic address: holm.uhlig@ndm.ox.ac.uk.
University of Oxford · GBIcahn School of Medicine at Mount Sinai · USBroad Institute · USHumboldt-Universität zu Berlin · DEWellcome Sanger Institute · GBBirmingham Children's Hospital · GBBoston Children's Hospital · USCedars-Sinai Medical Center · USEuropean Bioinformatics Institute · GBEvelina London Children's Healthcare · GBGarvan Institute of Medical Research · AULudwig-Maximilians-Universität München · DETel Aviv University · ILUniversity of Cambridge · GBUniversity of Manchester · GBUniversity of Toronto · CAUniversity of Warmia and Mazury in Olsztyn · PL

Funding

COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8M
Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel DiseaseRC2DK122532 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI KLEIN, CHRISTOPH, MUISE, ALEIXO M · 2020 to 2024
$9.1M
CIHRDepartment of HealthHoward Hughes Medical InstituteMedical Research Council MR/T001917/1NIDDK NIH HHS RC2 DK118640NIDDK NIH HHS RC2 DK122532Wellcome Trust 211276
6 · The paper itself

Abstract

BACKGROUND &

aimsMonogenic forms of inflammatory bowel disease (IBD) illustrate the essential roles of individual genes in pathways and networks safeguarding immune tolerance and gut homeostasis.

methodsTo build a taxonomy model, we assessed 165 disorders. Genes were prioritized based on penetrance of IBD and disease phenotypes were integrated with multi-omics datasets. Monogenic IBD genes were classified by (1) overlapping syndromic features, (2) response to hematopoietic stem cell transplantation, (3) bulk RNA-sequencing of 32 tissues, (4) single-cell RNA-sequencing of >50 cell subsets from the intestine of healthy individuals and patients with IBD (pediatric and adult), and (5) proteomes of 43 immune subsets. The model was validated by addition of newly identified monogenic IBD defects. As a proof-of-concept, we explore the intersection between immunometabolism and antimicrobial activity for a group of disorders (G6PC3/SLC37A4).

resultsOur quantitative integrated taxonomy defines the cellular landscape of monogenic IBD gene expression across 102 genes with high and moderate penetrance (81 in the model set and 21 genes in the validation set). We illustrate distinct cellular networks, highlight expression profiles across understudied cell types (e.g., CD8

conclusionOur taxonomy integrates genetic, clinical and multi-omic data; providing a basis for genomic diagnostics and testable hypotheses for disease functions and treatment responses.

Indexed as

Age of OnsetAntiportersCells, CulturedClassificationGene Expression ProfilingGenetic Association StudiesGenotypeGlucose-6-PhosphataseGlucose-6-PhosphateHumansInflammatory Bowel DiseasesMacrophagesMetabolomicsMonosaccharide Transport ProteinsPenetrancePhenotypeAntiportersG6PC3 protein, humanGlucose-6-PhosphataseGlucose-6-PhosphateMonosaccharide Transport ProteinsSLC37A4 protein, humanGenomicsImmunodeficiencyNext-Generation SequencingRNA-seq

Identifiers

PMID34780721
PMCPMC7616885
OpenAlexW3213330452

What OpenQuestion holds

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Registered trials

None linked

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.