NDLI: Network medicine analysis of chondrocyte proteins towards new treatments of osteoarthritis

Content Provider	PubMed Central
Author	Nacher, Jose C. Keith, Benjamin Schwartz, Jean-marc
Copyright Year	2014
Abstract	Osteoarthritis (OA) is a progressive disorder with high incidence in the ageing human population that still has no treatment currently. This disorder induces the breakdown of articular cartilage, leading to the exposure and damage of bone surfaces. For a global understanding of OA development, the systematic integration of known OA-related proteins with protein–protein interaction (PPI) networks is required. In this work, the OA-related interactome was reconstructed using multiple data sources to have the most up-to-date information on OA-related proteins and their interactions. We then combined emergent concepts in network medicine to detect new unclassified OA-related proteins. The mapping of known OA-related proteins with PPI networks showed that these proteins are locally connected to each other and agglomerated in a large component. To expand this module, we applied a diffusion-based algorithm that probabilistically induces more searches in the vicinity of the seed OA-related proteins. As a result, the 10 topmost ranked proteins were connected to the OA disease module, supporting the local hypothesis. We computed structural modules and selected those that had the highest enrichment of OA-related proteins. The identified molecules show a link between structural topology and disease dysfunctionality. Interestingly, the protein Q6EEV6 was highlighted for OA association by both methods, reinforcing the potential involvement of this protein. These results suggest that similar disease-connected modules may exist in different human disorders, which could lead to systematic identification of genes or proteins that have a joint role in specific disease phenotypes.
Related Links	http://dx.doi.org/10.1098/rspb.2013.2907
Starting Page	20132907
File Format	PDF
ISSN	09628452
e-ISSN	14712954
Journal	Proceedings of the Royal Society B: Biological Sciences
Issue Number	1778
Volume Number	281
Language	English
Publisher	The Royal Society
Publisher Date	2014-01-15
Access Restriction	Open
Rights Holder	The Royal Society
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Agricultural and Biological Sciences(all) Environmental Science(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology Environmental Science Agricultural and Biological Sciences

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