Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis.
Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis.
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DOI：
10.1136/thoraxjnl-2018-211929
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发表时间：
2019-03
期刊：
影响因子：
10
通讯作者：
Wuyts WA
中科院分区：
文献类型：
--
作者：
McDonough JE;Kaminski N;Thienpont B;Hogg JC;Vanaudenaerde BM;Wuyts WA
特发性肺纤维化（IPF）是一种以广泛病理改变为特征的严重肺部疾病。本研究的目的是确定IPF疾病病理基础的基因网络和调节因子及其与肺功能的相关性。将包含262名IPF和对照受试者（GSE 47460）的Lung Tissue Research Consortium数据集随机分为两个非重叠组，用于交叉验证的差异基因表达分析。共识加权基因共表达网络分析确定了两个IPF组之间重叠的共表达基因模块。模块与肺功能（弥散容量，DLCO; 1秒用力呼气量，FEV 1;用力肺活量，FVC）相关，富集分析用于识别生物功能和转录因子。与miRNA数据（GSE 72967）的模块相关性鉴定了相关的调节子。在外周血基因表达数据集（GSE 93606）中评估IPF的临床相关性，以确定与生存相关的模块。相关网络分析确定了IPF的16个模块。上调的模块与纤毛，DNA复制和修复，收缩纤维，B细胞和未折叠的蛋白质反应，和细胞外基质。下调模块与血管，T细胞和干扰素反应，白细胞活化和脱粒，表面活性剂代谢，细胞代谢和分解代谢过程。肺功能与9个模块相关（8个与DLCO相关，5个与FVC相关）。转录因子和miRNA的模块间网络显示了纤维化、免疫反应和收缩模块的聚集。纤毛相关模块能够预测独立外周血IPF队列的生存率（p=0.0097）。我们确定了一个相关基因表达网络与相关的调节因子在IPF，提供了新的见解，这种疾病的病理过程。
Idiopathic pulmonary fibrosis (IPF) is a severe lung disease characterised by extensive pathological changes. The objective for this study was to identify the gene network and regulators underlying disease pathology in IPF and its association with lung function. Lung Tissue Research Consortium dataset with 262 IPF and control subjects (GSE47460) was randomly divided into two non-overlapping groups for cross-validated differential gene expression analysis. Consensus weighted gene coexpression network analysis identified overlapping coexpressed gene modules between both IPF groups. Modules were correlated with lung function (diffusion capacity, DLCO; forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC) and enrichment analyses used to identify biological function and transcription factors. Module correlation with miRNA data (GSE72967) identified associated regulators. Clinical relevance in IPF was assessed in a peripheral blood gene expression dataset (GSE93606) to identify modules related to survival. Correlation network analysis identified 16 modules in IPF. Upregulated modules were associated with cilia, DNA replication and repair, contractile fibres, B-cell and unfolded protein response, and extracellular matrix. Downregulated modules were associated with blood vessels, T-cell and interferon responses, leucocyte activation and degranulation, surfactant metabolism, and cellular metabolic and catabolic processes. Lung function correlated with nine modules (eight with DLCO, five with FVC). Intermodular network of transcription factors and miRNA showed clustering of fibrosis, immune response and contractile modules. The cilia-associated module was able to predict survival (p=0.0097) in an independent peripheral blood IPF cohort. We identified a correlation gene expression network with associated regulators in IPF that provides novel insight into the pathological process of this disease.
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影响因子：
32.4
作者：
Wang L;Wildt KF;Castro E;Xiong Y;Feigenbaum L;Tessarollo L;Bosselut R
通讯作者：
Bosselut R
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
14.9
作者：
Reimand J;Arak T;Adler P;Kolberg L;Reisberg S;Peterson H;Vilo J
通讯作者：
Vilo J
影响因子：
3.7
作者：
Seibold MA;Smith RW;Urbanek C;Groshong SD;Cosgrove GP;Brown KK;Schwarz MI;Schwartz DA;Reynolds SD
通讯作者：
Reynolds SD