Identification of common key genes and pathways between type 1 diabetes and multiple sclerosis using transcriptome and interactome analysis

Abstract

Abstract Purpose Type 1 diabetes (T1D) and multiple sclerosis (MS) are classified as T cell-mediated autoimmune diseases. Although convergent evidence proposed common genetic architecture for autoimmune diseases, it remains a challenge to identify them. This study aimed to determine common gene signature and pathways in T1D and MS via systems biology approach. Methods Gene expression profiles of peripheral blood mononuclear cells (PBMCs) and pancreatic-β cells in T1D as well as PBMCs and cerebrospinal fluid (CSF) in MS were analyzed in our previous published data, and differential expressed genes were integrated with protein–protein interactions data to construct Query–Query PPI (QQPPI) networks. In this study, QQPPI networks were further analyzed to investigate more central genes, functional modules and complexes shared in T1D and MS progression. Lastly, the interaction of common genes with drugs was also explored. Results Several cytokines such as IL-23A, IL-32, IL-34, and IL-37 tend to be differentially expressed in both diseases. In addition, PSMA1, MYC, SRPK1, YBX1, HNRNPM, NF-κB2, IKBKE, RAC1, FN1, ARRB2, ESR1, HSP90AB1, and PPP1CA were common high central genes in QQPPI networks corresponding to each disease. Proteasome, spliceosome, immune responses, apoptosis, cellular communication/signaling transduction mechanism, interaction with environment, and activity of intercellular mediators were shared biological processes in T1D and MS. Finally, azathioprine, melatonin, resveratrol, and geldanamycin identified as prioritized drugs for the treatment of patients with T1D and MS. Conclusions This study represented novel key genes and pathways shared between T1D and MS, which may facilitate the identification of potential therapeutic targets in these diseases.