Dynamic tracking of functional gene modules in treated juvenile idiopathic arthritis.
BACKGROUND
We have previously shown that childhood-onset rheumatic diseases show aberrant patterns of gene expression that reflect pathology-associated co-expression networks. In this study, we used novel computational approaches to examine how disease-associated networks are altered in one of the most common rheumatic diseases of childhood, juvenile idiopathic arthritis (JIA).


METHODS
Using whole blood gene expression profiles derived from children in a pediatric rheumatology clinical trial, we used a network approach to understanding the impact of therapy and the underlying biology of response/non-response to therapy.


RESULTS
We demonstrate that therapy for JIA is associated with extensive re-ordering of gene expression networks, even in children who respond inadequately to therapy. Furthermore, we observe distinct differences in the evolution of specific network properties when we compare children who have been treated successfully with those who have inadequate treatment response.


CONCLUSIONS
Despite the inherent noisiness of whole blood gene expression data, our findings demonstrate how therapeutic response might be mapped and understood in pathologically informative cells in a broad range of human inflammatory diseases.
Department of Computer Sciences and Engineering, University at Buffalo, Buffalo, NY, USA. nandu2048@gmail.com.
Nan
N
Du
Department of Pediatrics, Rheumatology Research, University at Buffalo School of Medicine, Buffalo, NY, USA. kaiyujia@buffalo.edu.
Kaiyu
K
Jiang
The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA. ads2202@columbia.edu.
Ashley D
AD
Sawle
Oklahoma Medical Research Foundation, Clinical Immunology Program, Oklahoma City, OK, USA. bart-frank@omrf.org.
Mark Barton
MB
Frank
Department of Pediatrics, University of Washington, Seattle, WA, USA. cwallace@u.washington.edu.
Carol A
CA
Wallace
Department of Computer Sciences and Engineering, University at Buffalo, Buffalo, NY, USA. azhang@buffalo.edu.
Aidong
A
Zhang
Department of Pediatrics, Rheumatology Research, University at Buffalo School of Medicine, Buffalo, NY, USA. jamesjar@buffalo.edu.|Genetics, Genomics, and Bioinformatics Program, University at Buffalo, Buffalo, NY, USA. jamesjar@buffalo.edu.|Pediatric Rheumatology Research, University at Buffalo Clinical & Translational Research Center, 875 Ellicott St, Buffalo, NY, 14203, USA. jamesjar@buffalo.edu.
James N
JN
Jarvis
D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D017423:Sequence Analysis, RNA; D059467:Transcriptome
D018501:Antirheumatic Agents; D000068800:Etanercept; D011241:Prednisone; D008727:Methotrexate