Integrative Analysis of Whole Exome Sequencing and Gene Expression to Uncover Genetic Mechanisms in Inflammatory Bowel Disease.
8 affiliations
- 1Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 2Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 3Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 4Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 5Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 6Department of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 7Department of Medical Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
- 8Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Abstract
Background/Objectives: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract. This study aimed to nominate candidate genes and pathways for IBD by integrating exome sequencing and gene expression data. Methods: Whole-exome sequencing (WES) was performed on 10 patients with Crohn's disease (CD). Differential expression was analyzed with GEO2R in an independent RNA-seq dataset (GSE193677; 2490 biopsies from 1162 subjects). Immune-related differentially expressed genes (DEGs) were identified with ImmPort, hub genes by protein-protein interaction analysis, and enriched pathways with Enrichr. Missense variants were modeled with AlphaFold 3. Results: WES identified 484 genes with rare coding variants in all 10 patients, and 732 genes were differentially expressed in CD or ulcerative colitis, 234 of them immune-related. Network, pathway, and database filtering prioritized ATM, CSF1R, FN1, and IL11, which together carry eight rare missense variants, with in silico predictions ranging from tolerated to deleterious. Enriched pathways included cytokine and interleukin signaling, and structural modeling predicted conformational changes. Conclusions: ATM, CSF1R, FN1, and IL11 are candidate genes in immune-related pathways in IBD. Because the genomic and expression data came from different cohorts, these genes need replication and experimental validation.
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BibTeX
@article{banaganapalli2026integrative,
title = {{Integrative Analysis of Whole Exome Sequencing and Gene Expression to Uncover Genetic Mechanisms in Inflammatory Bowel Disease.}},
author = {Babajan Banaganapalli and Waad Fahad Alharbi and Wejdan Abdullah Alzahrani and Ashraf A El-Harouni and Mahmoud Almutadares and Khalidah Khalid Nasser and Omar I Saadah and Mahmoud Mosli and Ragdah Hussain Arif and Hadeel A Alsufyani and Dareen Alyousfi and Noor Ahmad Shaik},
journal = {Genes},
year = {2026},
month = oct,
doi = {10.3390/genes17101306},
url = {https://europepmc.org/article/MED/42938422},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrative Analysis of Whole Exome Sequencing and Gene Expression to Uncover Genetic Mechanisms in Inflammatory Bowel Disease.
AU - Babajan Banaganapalli
AU - Waad Fahad Alharbi
AU - Wejdan Abdullah Alzahrani
AU - Ashraf A El-Harouni
AU - Mahmoud Almutadares
AU - Khalidah Khalid Nasser
AU - Omar I Saadah
AU - Mahmoud Mosli
AU - Ragdah Hussain Arif
AU - Hadeel A Alsufyani
AU - Dareen Alyousfi
AU - Noor Ahmad Shaik
PY - 2026
DA - 2026/10/20
JO - Genes
DO - 10.3390/genes17101306
UR - https://europepmc.org/article/MED/42938422
AB - Background/Objectives: Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract. This study aimed to nominate candidate genes and pathways for IBD by integrating exome sequencing and gene expression data. Methods: Whole-exome sequencing (WES) was performed on 10 patients with Crohn's disease (CD). Differential expression was analyzed with GEO2R in an independent RNA-seq dataset (GSE193677; 2490 biopsies from 1162 subjects). Immune-related differentially expressed genes (DEGs) were identified with ImmPort, hub genes by protein-protein interaction analysis, and enriched pathways with Enrichr. Missense variants were modeled with AlphaFold 3. Results: WES identified 484 genes with rare coding variants in all 10 patients, and 732 genes were differentially expressed in CD or ulcerative colitis, 234 of them immune-related. Network, pathway, and database filtering prioritized ATM, CSF1R, FN1, and IL11, which together carry eight rare missense variants, with in silico predictions ranging from tolerated to deleterious. Enriched pathways included cytokine and interleukin signaling, and structural modeling predicted conformational changes. Conclusions: ATM, CSF1R, FN1, and IL11 are candidate genes in immune-related pathways in IBD. Because the genomic and expression data came from different cohorts, these genes need replication and experimental validation.
SN - 2073-4425
ER -