title: A systems approach to rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily attacks synovial joints. Despite the advances in diagnosis and treatment of RA, novel molecular targets are still needed to improve the accuracy of diagnosis and the therapeutic outcomes. Here, we present a systems approach that can effectively 1) identify core RA-associated genes (RAGs), 2) reconstruct RA-perturbed networks, and 3) select potential targets for diagnosis and treatments of RA. By integrating multiple gene expression datasets previously reported, we first identified 983 core RAGs that show RA dominant differential expression, compared to osteoarthritis (OA), in the multiple datasets. Using the core RAGs, we then reconstructed RA-perturbed networks that delineate key RA associated cellular processes and transcriptional regulation. The networks revealed that synovial fibroblasts play major roles in defining RA-perturbed processes, anti-TNF-α therapy restored many RA-perturbed processes, and 19 transcription factors (TFs) have major contribution to deregulation of the core RAGs in the RA-perturbed networks. Finally, we selected a list of potential molecular targets that can act as metrics or modulators of the RA-perturbed networks. Therefore, these network models identify a panel of potential targets that will serve as an important resource for the discovery of therapeutic targets and diagnostic markers, as well as providing novel insights into RA pathogenesis.
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, POSTECH, Pohang, Korea.
authors.forename: Sungyong
authors.initials: S
authors.lastname: You
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Inyoul
authors.initials: I
authors.lastname: Lee
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D058990:Molecular Targeted Therapy; D010003:Osteoarthritis / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism; D049490:Systems Biology; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha