Network Biology Analysis of the Human Abdominal Aortic Aneurysm Plasma Proteome

Objective: Abdominal aortic aneurysm (AAA) affects up to 9% of adults, and the incidence of asymptomatic and ruptured AAA currently accounts for 1–2% of male deaths. A number of studies have applied classical proteomics methodology to identify plasma biomarkers of AAA. The use of a systems biology protein-protein interaction network analysis on proteomics results can reveal novel mechanisms. Methods: We performed a bioinformatics analysis on a compiled set of proteins previously identified in multiple proteomics studies. Results from a total of nine papers were identified and included in the analysis. The 64 proteins related to AAA were first analyzed by over-representation analysis (ORA) using Webgestalt. Afterwards, the same input list was submitted to BioProfiling. This portal used statistical methodology for the network based interpretation of the protein list (Rspider, PPIspider). The networks obtained by both Reactome and PPI analysis were further analyzed by ORA using the JEPETTO application in the Cytoscape environment. Results: This analysis revealed a strong over-representation for proteins related not only to blood clotting but also to cellular mediated response, such as cell adhesion and cytokine activation of platelets and white blood cells. Conclusions: We used a network strategy to generate statistically valid novel hypotheses about biological mechanisms related to AAA, which may be useful in providing new insights into the understanding of the pathogenesis of AAA.