Endophenotype Network Models: Common Core of Complex Diseases

Susan Dina Ghiassian, Jörg Menche, Daniel I. Chasman, Franco Giulianini, Ruisheng Wang, Piero Ricchiuto, Masanori Aikawa, Hiroshi Iwata, Christian Müller, Tania Zeller, Amitabh Sharma, Philipp Wild, Karl Lackner, Sasha Singh, Paul M. Ridker, Stefan Blankenberg, Albert László Barabási, Joseph Loscalzo

Research output: Contribution to journalArticlepeer-review

Abstract (may include machine translation)

Historically, human diseases have been differentiated and categorized based on the organ system in which they primarily manifest. Recently, an alternative view is emerging that emphasizes that different diseases often have common underlying mechanisms and shared intermediate pathophenotypes, or endo(pheno)types. Within this framework, a specific disease's expression is a consequence of the interplay between the relevant endophenotypes and their local, organ-based environment. Important examples of such endophenotypes are inflammation, fibrosis, and thrombosis and their essential roles in many developing diseases. In this study, we construct endophenotype network models and explore their relation to different diseases in general and to cardiovascular diseases in particular. We identify the local neighborhoods (module) within the interconnected map of molecular components, i.e., the subnetworks of the human interactome that represent the inflammasome, thrombosome, and fibrosome. We find that these neighborhoods are highly overlapping and significantly enriched with disease-associated genes. In particular they are also enriched with differentially expressed genes linked to cardiovascular disease (risk). Finally, using proteomic data, we explore how macrophage activation contributes to our understanding of inflammatory processes and responses. The results of our analysis show that inflammatory responses initiate from within the cross-talk of the three identified endophenotypic modules.

Original languageEnglish
Article number27414
JournalScientific Reports
Volume6
DOIs
StatePublished - 9 Jun 2016

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