Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach

BackgroundUnderstanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic target...

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Main Authors: Edia Stemmer, Tamar Zahavi, Maoz Kellerman, Liat Anabel Sinberger, Guy Shrem, Mali Salmon‐Divon
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353402/full
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author Edia Stemmer
Tamar Zahavi
Maoz Kellerman
Maoz Kellerman
Liat Anabel Sinberger
Guy Shrem
Mali Salmon‐Divon
Mali Salmon‐Divon
author_facet Edia Stemmer
Tamar Zahavi
Maoz Kellerman
Maoz Kellerman
Liat Anabel Sinberger
Guy Shrem
Mali Salmon‐Divon
Mali Salmon‐Divon
author_sort Edia Stemmer
collection DOAJ
description BackgroundUnderstanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease.MethodsTo obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques.ResultsWe analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn’s disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment.ConclusionOur findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.
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spelling doaj.art-5004e7c9dfc54edc819a269439ccc84a2024-03-06T05:01:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13534021353402Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approachEdia Stemmer0Tamar Zahavi1Maoz Kellerman2Maoz Kellerman3Liat Anabel Sinberger4Guy Shrem5Mali Salmon‐Divon6Mali Salmon‐Divon7Department of Molecular Biology, Ariel University, Ariel, IsraelDepartment of Molecular Biology, Ariel University, Ariel, IsraelDepartment of Molecular Biology, Ariel University, Ariel, IsraelKaleidoo, Bar Lev High Tech Park, Misgav, IsraelDepartment of Molecular Biology, Ariel University, Ariel, IsraelObstetrics, Gynecology and Infertility (OB&GYN) Department Maccabi Healthcare Services, Tel Aviv, IsraelDepartment of Molecular Biology, Ariel University, Ariel, IsraelAdelson School of Medicine, Ariel University, Ariel, IsraelBackgroundUnderstanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease.MethodsTo obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques.ResultsWe analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn’s disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment.ConclusionOur findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353402/fullinflammatory bowel diseaseulcerative colitisCrohn’s diseasebiomarkersmega-analysismachine learning
spellingShingle Edia Stemmer
Tamar Zahavi
Maoz Kellerman
Maoz Kellerman
Liat Anabel Sinberger
Guy Shrem
Mali Salmon‐Divon
Mali Salmon‐Divon
Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach
Frontiers in Immunology
inflammatory bowel disease
ulcerative colitis
Crohn’s disease
biomarkers
mega-analysis
machine learning
title Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach
title_full Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach
title_fullStr Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach
title_full_unstemmed Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach
title_short Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach
title_sort exploring potential biomarkers and therapeutic targets in inflammatory bowel disease insights from a mega analysis approach
topic inflammatory bowel disease
ulcerative colitis
Crohn’s disease
biomarkers
mega-analysis
machine learning
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1353402/full
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