Identification of dysregulated pathways underlying HTLV-1-associated myelopathy/tropical spastic paraparesis through co-expression network analysis

Human T cell lymphotropic virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a pathogen-caused disease which is associated with the progressive neurological disorder. HAM/TSP affects the expression level of several proteins and dysregulates some biological pathways. To identify the interaction patterns among expressed genes in HAM/TSP patients, weighted gene co-expression network analysis (WGCNA) was applied. Three microarray datasets regarding HAM/TSP were merged, and the co-expression network was constructed among genes. A total of 38 modules were identified. Three preserved modules in HAM/TSP in comparison to the healthy subjects which also had the most connected proteins and enriched in the biological pathways were selected. These modules were enriched in pathways related to immune systems, cell cycle, viral infection, and neuronal systems. Moreover, the involvement of novel immunological-related proteins including C1QB, GBP5, PSME1, SERPING1, and UBE2C; neurological-related proteins including TUBA4A, TUBB8, and TP63; and also proteins including TRPC6, PRKG2, OPRD1, PRKACA, and TUBB4A involved in the cGMP-PKG signaling pathway, thyroid hormone synthesis, and recruitment of mitotic centrosome proteins and complexes were found. Therefore, tracing these proteins and the identified modules can shed light on the pathogenesis mechanism of HAM/TSP and help to find potential therapeutic targets. However, further experimental validation should be performed to confirm the proposed functional players.