Abstract

Type 1 diabetes (T1D) is a complex disease, caused by the autoimmune destruction of the insulin producing pancreatic beta cells, resulting in the body’s inability to produce insulin. While great efforts have been put into understanding the genetic and environmental factors that contribute to the etiology of the disease, the exact molecular mechanisms are still largely unknown. T1D is a heterogeneous disease, and previous research in this field is mainly focused on the analysis of single genes, or using traditional gene expression profiling, which generally does not reveal the functional context of a gene associated with a complex disorder. However, network-based analysis does take into account the interactions between the diabetes specific genes or proteins and contributes to new knowledge about disease modules, which in turn can be used for identification of potential new biomarkers for T1D. In this study, we analyzed public microarray data of T1D patients and healthy controls by applying a systems biology approach that combines network-based Weighted Gene Co-Expression Network Analysis (WGCNA) with functional enrichment analysis. Novel co-expression gene network modules associated with T1D were elucidated, which in turn provided a basis for the identification of potential pathways and biomarker genes that may be involved in development of T1D.

Highlights

  • Type 1 diabetes (T1D) is a complex trait, which develops when the insulin producing beta cells are destroyed resulting in a decreased production and secretion of insulin

  • Besides confirming some genes with previously known T1D involvement, such as fas cell surface death receptor (FAS), interleukin 1 beta (IL1B) and interleukin 8 (IL8), we identified interesting candidate genes that could be further analyzed further to understand their roles in T1D

  • Functional enrichment analysis of this module was performed with EnrichNet and ConsensusPathDB

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Summary

Introduction

Type 1 diabetes (T1D) is a complex trait, which develops when the insulin producing beta cells are destroyed resulting in a decreased production and secretion of insulin. According to National Center for Chronic Disease Prevention and Health Promotion (CDC), diabetes is one of the most common chronic diseases worldwide, having a prevalence of 9.3% of the population in United States [1]. Diabetes is a major contributor of renal diseases, amputation, cardiovascular disease [2,3], and has been projected to be the seventh leading cause of deaths in 2030 [4]. T1D is a heterogeneous disease with both underlying genetic and environmental factors that influence the development and progression of the disease [5]. PLOS ONE | DOI:10.1371/journal.pone.0156006 June 3, 2016

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