Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation
Abstract
:1. Introduction
2. Results
2.1. Data Preprocessing and Meta-Analysis of Differentially Expressed Genes (DEGs)
2.2. Functional and Pathway Enrichment Analysis
2.3. Protein–Protein Interaction Network (PPI) Construction and IBD-DEG Identification
2.4. Disease Modules Screening and Identification of Potential Key Disease-Associated Genes
2.5. Immune Cell Infiltration Landscape
3. Discussion
4. Materials and Methods
4.1. Datasets Collection
4.2. Gene Expression Datasets Preprocessing and Identification of DEGs
4.3. Meta-Analysis of DEGs and Tissue Mapping of the Identified DEGs
4.4. Functional Enrichment Analysis
4.5. Protein–Protein Interaction Network (PPI) and Selection of IBD Key Genes
4.6. CIBERSORTx Estimation of Immune Cell Infiltration
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Datasets | |||||
ID | Inflamed | Non-Inflamed | Platform | References | |
CD | GSE83687 | 42 | 60 | Illumina HiSeq 2500 | [14] |
GSE179285 | 47 | 121 | Agilent-014850 Whole Human Genome | [15] | |
GSE186582 | 137 | 94 | Affymetrix Human Genome U133 Plus 2.0 Array | [16] | |
GSE75214 | 59 | 16 | Affymetrix Human Gene 1.0 ST Array | [17] | |
UC | GSE9452 | 8 | 18 | Affymetrix Human Genome U133 Plus 2.0 Array | [18] |
GSE75214 | 74 | 23 | Affymetrix Human Gene 1.0 ST Array | [17] | |
GSE48958 | 7 | 6 | Affymetrix Human Gene 1.0 ST Array | [19] | |
GSE179285 | 23 | 32 | Agilent-014850 Whole Human Genome | [15] | |
Total | 397 | 370 | For Meta-analysis | ||
Validation Datasets | |||||
ID | Patients | Healthy | Platform | ||
IBD | GSE117993 | 135 | 55 | Illumina HiSeq 2500 (Homo sapiens) | [20] |
GSE4183 | 15 | 8 | Affymetrix Human Genome U133 Plus 2.0 Array | [21] | |
GSE13367 | 8 | 10/9 1 | Affymetrix Human Genome U133 Plus 2.0 Array | [22] | |
GSE16879 | 98 | 12 | Affymetrix Human Genome U133 Plus 2.0 Array | [23] | |
GSE36807 | 28 | 7 | Affymetrix Human Genome U133 Plus 2.0 Array | [8] | |
GSE38713 | 23 | 13 | Affymetrix Human Genome U133 Plus 2.0 Array | [24] | |
GSE6731 | 12 | 17 | Affymetrix Human Genome U95 Version 2 Array | [25] | |
GSE59071 | 82 | 11/23 2 | Affymetrix Human Gene 1.0 ST Array | [26] |
Findings | Key Points |
---|---|
DEGs Identified Through Meta-analysis | 180 common DEGs were identified between CD and UC |
Key Disease-Related Genes | Nine potential IBD modulators (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, PCK1) |
Pathways Involved | TNF signaling, adipocytokine signaling, colorectal cancer, leukocyte transendothelial migration, NOD-like receptor signaling, and VEGF signaling |
Phenotypic Traits | Dysregulated inflammatory response, impaired oxidative burst, increased susceptibility to infection, and recurrent abscess formation |
Increased Immune Infiltration | Neutrophils, activated DCs, plasma cells, mast cells (resting/activated), B cells (memory/naïve), Tregs, M0 and M1 macrophages |
Reduced Immune Infiltration | Monocytes, activated NK cells, resting DCs, M2 macrophages, T cells (gamma delta, follicular helper, CD8, and CD4 memory resting) |
No Change | Resting NK cells, T cells CD4 (naïve/memory activated), and eosinophils |
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Alghamdi, K.S.; Kassar, R.H.; Farrash, W.F.; Obaid, A.A.; Idris, S.; Siddig, A.; Shakoori, A.M.; Alshehre, S.M.; Minshawi, F.; Mujalli, A. Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation. Int. J. Mol. Sci. 2024, 25, 9751. https://doi.org/10.3390/ijms25179751
Alghamdi KS, Kassar RH, Farrash WF, Obaid AA, Idris S, Siddig A, Shakoori AM, Alshehre SM, Minshawi F, Mujalli A. Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation. International Journal of Molecular Sciences. 2024; 25(17):9751. https://doi.org/10.3390/ijms25179751
Chicago/Turabian StyleAlghamdi, Kawthar S., Rahaf H. Kassar, Wesam F. Farrash, Ahmad A. Obaid, Shakir Idris, Alaa Siddig, Afnan M. Shakoori, Sallwa M. Alshehre, Faisal Minshawi, and Abdulrahman Mujalli. 2024. "Key Disease-Related Genes and Immune Cell Infiltration Landscape in Inflammatory Bowel Disease: A Bioinformatics Investigation" International Journal of Molecular Sciences 25, no. 17: 9751. https://doi.org/10.3390/ijms25179751