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For a global understanding of OA development, the systematic integration of known OA-related proteins with protein\u2013protein 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.<\/jats:p>","DOI":"10.1098\/rspb.2013.2907","type":"journal-article","created":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T10:14:15Z","timestamp":1389780855000},"page":"20132907","update-policy":"http:\/\/dx.doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Network medicine analysis of chondrocyte proteins towards new treatments of osteoarthritis"],"prefix":"10.1098","volume":"281","author":[{"given":"Jose C.","family":"Nacher","sequence":"first","affiliation":[{"name":"Department of Information Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Keith","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Marc","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2014,3,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290816"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2008.09.011"},{"key":"e_1_3_3_4_2","volume-title":"Arthritis and allied conditions: a textbook of rheumatology","author":"Koopman WJ","year":"2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950171208"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar148"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2918"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.01.016"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.041376"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404315101"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/504300"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq076"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1295"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.02.013"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000641"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-7552(98)00110-X"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","DOI":"10.1515\/9781400830329","volume-title":"Google's PageRank and beyond: the science of search engine rankings","author":"Langville AN","year":"2006"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-73"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq680"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054204"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010137"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-7-10"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.02.482"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn892"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1171104"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2172"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27265"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2007.12.003"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1002\/art.27491","article-title":"Granulin-epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein","volume":"62","author":"Guo F","year":"2010","journal-title":"Arthritis Rheum."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.06.005"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1002\/elps.200890074","article-title":"Micro-high-performance liquid chromatography platform for the depletion of high-abundance proteins and subsequent on-line concentration\/capturing of medium- and low-abundance proteins from serum. 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