RT Journal Article SR Electronic T1 Integrated molecular phenotyping identifies genes and pathways disrupted in osteoarthritis JF bioRxiv FD Cold Spring Harbor Laboratory SP 038067 DO 10.1101/038067 A1 Graham R. S. Ritchie A1 Theodoros I. Roumeliotis A1 Julia Steinberg A1 Abbie L. A. Binch A1 Rachael Coyle A1 Mercedes Pardo A1 Christine L. Le Maitre A1 Jyoti S. Choudhary A1 J. Mark Wilkinson A1 Eleftheria Zeggini YR 2016 UL http://biorxiv.org/content/early/2016/01/28/038067.abstract AB Osteoarthritis (OA) is a degenerative joint disease with substantial global health economic burden and no curative therapy. Here we investigate genes and pathways underpinning disease progression, combining methylation typing, RNA sequencing and quantitative proteomics in chondrocytes from matched damaged and healthy articular cartilage samples from OA patients undergoing knee replacement surgery. Our data highlight 49 genes differentially regulated at multiple levels, identifying 19 novel genes with a potential role in OA progression. An integrated pathway analysis identifies established and emerging biological processes. We perform an in silico search for drugs predicted to target the differentially regulated factors and identify several established therapeutic compounds which now warrant further investigation in OA. Overall this work provides a first integrated view of the molecular landscape of human primary chondrocytes and offers insights into the mechanisms of cartilage degeneration. The results point to new therapeutic avenues, highlighting the translational potential of integrated functional genomics. All data from these experiments are freely available for access in the appropriate repositories.