Novel putative drugs and key initiating genes for neurodegenerative disease determined using network-based genetic integrative analysis.

摘要: Understanding the genetic causes of neurodegenerative disease (ND) can be useful for their prevention and treatment. Among variations responsible ND, heritable germline variants have been discovered in genome-wide association studies (GWAS), nonheritable somatic mutations sequencing projects. Distinguishing important initiating genes ND comparing importance for treating are challenges. In this study, we analysed GWAS results, drug targets from large databanks by performing directed network-based analysis considering a randomised network hypothesis testing procedure. A disease-associated biological was created context functional interactome, nonrandom topological characteristics directed-edge classes were interpreted. Hierarchical indicated that tend to lie upstream variants. Furthermore, using path length information explanations, provide on most these node associated drugs. Finally, identified nine overlapping with seven close hierarchical six crucial controlling other analysis. Based findings, some drugs proposed treating via repurposing. Our results new insights into therapeutic actionability ND. The interesting properties each class existing relationships between them broaden our knowledge