Evidence map›Paper›PMID 36964596›Full record

ArticleClinical epigenetics2023

Longitudinal DNA methylation profiling of the rectal mucosa identifies cell-specific signatures of disease status, severity and clinical outcomes in ulcerative colitis cell-specific DNA methylation signatures of UC.

Suresh Venkateswaran, Hari K Somineni, Jason D Matthews, Varun Kilaru, Jeffrey S Hyams, Lee A Denson, Richard Kellamayer, Greg Gibson, David J Cutler, Karen N Conneely and 2 more

Open access · goldFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  9. Precision medicine in inflammatory bowel disease.Precision clinical medicine · 2023
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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

12 authors at 6 institutions in 1 country.

Suresh VenkateswaranDivision of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA.
Hari K SomineniDivision of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA.
Jason D MatthewsDivision of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA.
Varun KilaruDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
Jeffrey S HyamsDivision of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA.
Lee A DensonDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Richard KellamayerSection of Pediatric Gastroenterology, Texas Children's Hospital Baylor College of Medicine, Houston, TX, USA.
Greg GibsonCenter for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA, USA.
David J CutlerDepartment of Human Genetics, Emory University, Atlanta, GA, USA.
Karen N Conneely *Department of Human Genetics, Emory University, Atlanta, GA, USA.
Alicia K Smith *Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.
Subra Kugathasan *Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA. skugath@emory.edu.
Children's Healthcare of Atlanta · USEmory University · USBaylor College of Medicine · USCincinnati Children's Hospital Medical Center · USConnecticut Children's Medical Center · USGeorgia Institute of Technology · US

Funding

Predicting Response to Standardized Pediatric Colitis Therapy: PROTECT StudyU01DK095745 · NIDDK · CONNECTICUT CHILDREN'S MEDICAL CENTER · PI DENSON, LEE ARMISTEAD, HYAMS, JEFFREY SAMUEL · 2012 to 2016
$10.4M
Leveraging the epigenome of inflammatory bowel disease to gain mechanistic insights into disease pathophysiology”R21DK119997 · NIDDK · EMORY UNIVERSITY · PI KUGATHASAN, SUBRA · 2019 to 2020
$422k
NIDDK NIH HHS R21 DK119997NIDDK NIH HHS U01 DK095745
6 · The paper itself

Abstract

backgroundIn peripheral blood, DNA methylation (DNAm) patterns in inflammatory bowel disease patients reflect inflammatory status rather than disease status. Here, we examined DNAm in diseased rectal mucosa from ulcerative colitis (UC) patients, focusing on constituent cell types with the goal of identifying therapeutic targets for UC other than the immune system. We profiled DNAm of rectal mucosal biopsies of pediatric UC at diagnosis (n = 211) and non-IBD control (n = 85) patients and performed epigenome-wide association studies (EWAS) of specific cell types to understand DNAm changes in epithelial, immune and fibroblast cells across disease states, course, and clinical outcomes. We also examined longitudinal analysis on follow-up samples (n = 73), and comparisons were made among patients with clinical outcomes including those undergoing colectomy versus those who did not. Additionally, we included RNA-seq from the same subjects to assess the impact of CpG sites on the transcription of nearby genes during the disease course.

resultsAt diagnosis, UC rectal mucosa exhibited a lower proportion of epithelial cells and fibroblasts, and higher proportion of immune cells, in conjunction with variation in the DNAm pattern. While treatment had significant effects on the methylation signature of immune cells, its effects on fibroblasts and epithelial cells were attenuated. Individuals who required colectomy exhibited cell composition and DNAm patterns at follow-up more similar to disease onset than patients who did not require colectomy. Combining these results with gene expression profiles, we identify CpG sites whose methylation patterns are most consistent with a contribution to poor disease outcomes and could thus be potential therapeutic targets.

conclusionsCell-specific epigenetic changes in the rectal mucosa in UC are associated with disease severity and outcome. Current therapeutics may more effectively target the immune than the epithelial and fibroblast compartments.

Indexed as

Colitis, UlcerativeCrohn DiseaseChildDNA MethylationHumansMucous MembraneRectumChildrenEpigenetic changesInflammatory bowel diseasePredicting Response to Standardized Pediatric Colitis Therapy (PROTECT) studyRisk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease (RISK) study

Identifiers

PMID36964596
PMCPMC10039532
OpenAlexW4360825292

What OpenQuestion holds

Textfull text, public
LicenceCC BY
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Read underepoch 390

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.