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Network Cluster Analysis of PPI and Phenotype Ontology for Type 1 Diabetes Mellitus

Davood Zaeifi1, Mahnaz Azarnia1,2

  • 1Department of Cellular and Molecular Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran.

Iranian Journal of Biotechnology
|June 3, 2024
PubMed
Abstract

Insights

This study identifies key gene pathways and networks in Type 1 Diabetes Mellitus (T1DM), revealing IL-2 as a significant hotspot. Understanding these genetic factors offers potential for T1DM treatment and prevention strategies.

Area of Science:

  • Immunology
  • Genetics
  • Bioinformatics

Background:

  • Type 1 Diabetes Mellitus (T1DM) pathogenesis involves T-cell-mediated beta-cell destruction.
  • The complete etiology of T1DM remains incompletely understood.

Purpose of the Study:

  • To investigate key gene pathways and co-expression networks associated with T1DM.
  • To identify critical genetic regulators and molecular interactions in T1DM.

Main Methods:

  • Identified T1DM-associated genes from 13 databases.
  • Performed pathway enrichment analysis and protein-protein interaction network analysis.
  • Constructed gene co-expression networks, functional modules, and transcription factor networks.

Main Results:

  • Identified 172 expressed genes and four single nucleotide polymorphisms (SNPs) linked to T1DM.
  • Pathway analysis highlighted inflammatory bowel disease, T1DM, cytokine-cytokine interaction, Th17 cell differentiation, JAK-STAT signaling, and graft-versus-host disease.
  • Weighted correlation network analysis revealed a module strongly correlated with T1DM, enriched in T cell activation and immune regulation pathways. Key regulators included IRF2, IRF4, IRF8, and CDX2.

Conclusions:

  • Identified Interleukin-2 (IL-2) as a significant T1DM hotspot.
  • Highlighted the crucial roles of hub genes and transcription factors in this autoimmune disease.
  • Findings offer potential targets for T1DM treatment and prevention.
Keywords:
Autoimmune diseaseBiomarkerPPI networkSNPT1DM

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