Network strategy to investigate differential pathways in sporadic amyotrophic lateral sclerosis

Objective: The objective of this paper was to investigate differential pathways in sporadic amyotrophic lateral sclerosis (SALS) based on pathway network analysis. Materials and Methods: To achieve this goal, first, differentially expressed genes (DEGs) between SALS and normal controls were identified, and a target network was defined as DEGs correlated interactions from the search tool for the retrieval of interacting genes/proteins (STRING). Second, topological centrality analysis was conducted on the target network to identify hub genes and hub network. Third, pathway network was constructed by taking intersections of Reactome database and STRING protein-protein interaction network. Finally, based on extracting the common interactions between target network, hub network and pathway network, we built randomized network, performed randomization test, and denoted differential pathways and hub differential pathways with P < 0.05. Results: There were 485 DEGs and 627 interactions in the target network. The pathway network was comprised 117,370 interactions. What was more, we found that 217 pathways had intersections with the target network. By accessing randomization test and removing the intersected count <10, 21 differential pathways with P values were nearly to be 0 were obtained, of which 6 rightly were the hub differential pathways, such as gene expression, mRNA Splicing, and mRNA splicing-major pathway. Conclusion: We have investigated 217 differential pathways and 21 significant differential pathways between SALS and normal controls based on network strategy. The findings might provide potential biomarkers for detection and therapy of SALS clinically and give great insights to reveal molecular mechanism underlying this disease. However, how these pathways cooperated with each other is still not clear, and future study should focus on this aspect.