BioAcyl Corp
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Ghiassian, S. D., Menche, J., Chasman, D. I., & others. (2016). Endophenotype Network Models: Common Core of Complex Diseases. Sci. Rep. 6. Added by: Dr. Enrique Feoli (01/02/2021, 22:13) Last edited by: Dr. Enrique Feoli (01/02/2021, 23:05) |
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| Resource type: Journal Article DOI: 10.1038/srep27414 BibTeX citation key: Ghiassian2016 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Network Medicine Creators: Chasman, Ghiassian, Menche, others Collection: Sci. Rep. |
Views: 3/358
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| Abstract |
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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.
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| Notes |
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Topological characteristics of seed genes within the Human Interactome. (A) Venn diagram of inflammatory (red), thrombotic (blue), and fibrotic (orange) seed genes. (B–D) correspond to subgraphs of the human interactome containing inflammatory, thrombotic, and fibrotic seed genes, respectively. These genes form a giant connected component, suggesting the existence of a local network neighborhood enriched with inflammatory, thrombotic, and fibrotic genes. The randomized distribution of the LCC size is shown in the histograms. For the effect of literature bias, see SI.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
