Dynamic tracking of functional gene modules in treated juvenile idiopathic arthritis.
Dynamic tracking of functional gene modules in treated juvenile idiopathic arthritis.
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DOI：
10.1186/s13073-015-0227-2
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发表时间：
2015-10-24
期刊：
影响因子：
12.3
通讯作者：
Jarvis JN
中科院分区：
文献类型：
--
作者：
Du N;Jiang K;Sawle AD;Frank MB;Wallace CA;Zhang A;Jarvis JN
我们以前已经表明，儿童期发病的风湿性疾病表现出异常的基因表达模式，反映了病理相关的共表达网络。在这项研究中，我们使用了新的计算方法来研究疾病相关的网络是如何改变的一个最常见的风湿性疾病的儿童，青少年特发性关节炎（JIA）。我们在儿科风湿病临床试验中使用来自儿童的全血基因表达谱，使用网络方法来了解治疗的影响以及对治疗有反应/无反应的基础生物学。我们证明，JIA的治疗与基因表达网络的广泛重新排序有关，即使在对治疗反应不足的儿童中也是如此。此外，我们观察到的特定网络属性的演变明显的差异，当我们比较儿童谁已经成功地治疗与那些谁有不足的治疗反应。尽管全血基因表达数据存在固有的噪声，但我们的研究结果表明，在广泛的人类炎症性疾病中，治疗反应如何在病理信息细胞中进行映射和理解。
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). 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. 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. 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.