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In silico analysis reveals interrelation of enriched pathways and genes in type 1 diabetes

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Abstract

Type 1 diabetes (T1D) is a multifactorial, polygenic complex autoimmune disease damaging pancreatic islet β cells. Numerous genes linked to T1D have been discovered through genetical studies, GWAS and polymorphisms. Most genetical studies focused on independent genes while others overemphasized on SNPs. Here, a collective analysis of documented T1D-associated genes was performed using bioinformatics tools. Enriched biological pathways, functions, enrichment clustering, networks and interactomes were analysed. Besides, meta-analyses of T1D-associated genes and T1D-related genes from SNPs were investigated to find common genes, pathways, enrichment and interrelationships. Notable enriched pathways comprised of cytokine-mediated signalling, cytokine production, interferon gamma production, myeloid leukocyte activation, activation of immune response, lymphocyte activation, adaptive immune response, Th17 cell differentiation etc. Enrichment analysis of T1D-associated genes emphasized the role of immune-linked machineries in metabolism, disease progression and aetiology of type 1 diabetes. Interactome analysis revealed overrepresentation of T1D-associated genes compared with T1D-related genes from SNPs. MCODE components highlighted the significance of pathways linked to vitamin D metabolism, signalling by interleukins, toll-like receptors, chemokines, PD-1, NOTCH, antigen processes etc. About 153 genes from MCODE complexes representing enriched pathways of T1D-associated genes and T1D-related genes from SNPs play a crucial role and may be important for further investigations. The information may be valuable for designing precision medicine–based therapeutics.

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Acknowledgements

The author thanks Prof. Justin O’Sullivan of the Liggins Institute, University of Auckland, New Zealand for allowing use of some data of T1D-associated eQTLs and genes from his published work (Nyaga et al. 2018). The author is also grateful to the anonymous reviewers for their constructive comments.

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  1. Postgraduate Department of Botany, Life Sciences Block, Ramananda College, Bishnupur, West Bengal, 722122, India

    Saubashya Sur

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This study was conceived and designed by SS. All the bioinformatic analysis, manuscript drafting and editing was done by SS.

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Correspondence to Saubashya Sur.

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Sur, S. In silico analysis reveals interrelation of enriched pathways and genes in type 1 diabetes. Immunogenetics 72, 399–412 (2020). https://doi.org/10.1007/s00251-020-01177-3

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