Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers
Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers
复制标题
DOI：
10.1038/msb.2012.24
复制
发表时间：
2012-07-01
影响因子：
9.9
通讯作者：
Roberts, Christopher
中科院分区：
文献类型：
--
作者：
Wang, I-Ming;Zhang, Bin;Roberts, Christopher
通过分析从11种啮齿动物炎性疾病模型分离的9种不同组织中获得的12个表达谱数据集，鉴定了常见的炎性基因特征以及疾病特异性特征。炎症组特征与已知的药物靶标和与代谢紊乱和癌症相关的共表达基因模块显著重叠。该特征中的大部分基因在由多个独立的小鼠和人类队列构建的组织特异性贝叶斯网络（BN）中紧密连接。炎性组签名和相应的共有BN都高度富集支持为肥胖、脂肪因子、糖尿病、主动脉病变、骨、肌肉和胆固醇性状的因果关系的免疫应答相关基因，表明炎性组对于多种疾病的因果性质。将这种炎性组签名与BN整合，发现了151个关键驱动因素，这些驱动因素在对疾病表型的影响方面似乎比非驱动因素更具有生物学重要性。对这种炎症特征、其网络结构和关键驱动因素的识别不仅突出了共同的病因，而且还确定了各种常见疾病干预的潜在靶点。分子系统生物学8：594;在线发表2012年7月17日; doi：10.1038/msb.2012.24主题分类：代谢和调控网络;疾病的分子生物学
Common inflammatome gene signatures as well as disease-specific signatures were identified by analyzing 12 expression profiling data sets derived from 9 different tissues isolated from 11 rodent inflammatory disease models. The inflammatome signature significantly overlaps with known drug targets and co-expressed gene modules linked to metabolic disorders and cancer. A large proportion of genes in this signature are tightly connected in tissue-specific Bayesian networks (BNs) built from multiple independent mouse and human cohorts. Both the inflammatome signature and the corresponding consensus BNs are highly enriched for immune response-related genes supported as causal for adiposity, adipokine, diabetes, aortic lesion, bone, muscle, and cholesterol traits, suggesting the causal nature of the inflammatome for a variety of diseases. Integration of this inflammatome signature with the BNs uncovered 151 key drivers that appeared to be more biologically important than the non-drivers in terms of their impact on disease phenotypes. The identification of this inflammatome signature, its network architecture, and key drivers not only highlights the shared etiology but also pinpoints potential targets for intervention of various common diseases. Molecular Systems Biology 8: 594; published online 17 July 2012; doi:10.1038/msb.2012.24 Subject Categories: metabolic and regulatory networks; molecular biology of disease