Bioinformatics and Connectivity Map Analysis Suggest Viral Infection as a Critical Causative Factor of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a common autoimmune disease, and its prevalence is rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed the features of HT through bioinformatics analysis so as to identify the markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG-pathway-enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed a Gene Set Enrichment Analysis (GSEA) by using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, a connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with the general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. The GSEA results revealed activation of autoimmune-disease-related pathways and several viral-infection pathways. Autoimmune-disease and viral-infection pathways were highly interconnected by common genes, while the HLA genes, which are shared by both, were significantly upregulated. The CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor which responds to viral activity, might serve as potential marker of HT.