In silico analysis reveals interrelation of enriched pathways and genes in type 1 diabetes
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ORIGINAL ARTICLE
In silico analysis reveals interrelation of enriched pathways and genes in type 1 diabetes Saubashya Sur 1 Received: 8 July 2020 / Accepted: 25 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 cytokinemediated 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 T1Dassociated 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. Keywords Type 1 diabetes . Genes . Enrichment pathways . Immune response . Protein-protein interactions
Introduction Diabetes is known to affect more than 463 million people on a global scale (Saeedi et al. 2019). Type 1 diabetes (T1D) is an auto-immune disorder manifested by the destruction of insulin-producing pancreatic β cells (Mehers and Gillespie 2008; Sun et al. 2019). In T1D, pancreatic islets are specifically attacked by the host immune system thereby forcing a life-long requisite for exogenous insulin in the patients (Mehers and Gillespie 2008; Pociot 2017). T1D is an evolving common chronic disease in adults and children with Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00251-020-01177-3) contains supplementary material, which is available to authorized users. * Saubashya Sur [email protected] 1
Postgraduate Department of Botany, Life Sciences Block, Ramananda College, Bishnupur, West Bengal 722122, India
increasing annual incidence of 3–4% (Pociot 2017; Pillay et al. 2015). Epidemiological studies indicated that Caucasoid populations, especially in Northern Euro
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