Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease.
Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease.
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DOI:
10.3390/ijms23105447
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发表时间:
2022-05-13
影响因子:
5.6
通讯作者:
中科院分区:
文献类型:
--
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Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease characterized by irreversible scarring of the lung parenchyma leading to dyspnea, progressive decline in lung function, and respiratory failure. We analyzed lung transcriptomic data from independent IPF cohorts using weighted gene co-expression network analysis (WGCNA) to identify gene modules based on their preservation status in these cohorts. The consensus gene modules were characterized by leveraging existing clinical and molecular data such as lung function, biological processes, pathways, and lung cell types. From a total of 32 consensus gene modules identified, two modules were found to be significantly correlated with the disease, lung function, and preserved in other IPF datasets. The upregulated gene module was enriched for extracellular matrix, collagen metabolic process, and BMP signaling while the downregulated module consisted of genes associated with tube morphogenesis, blood vessel development, and cell migration. Using a combination of connectivity-based and trait-based significance measures, we identified and prioritized 103 “hub” genes (including 25 secretory candidate biomarkers) by their similarity to known IPF genetic markers. Our validation studies demonstrate the dysregulated expression of CRABP2, a retinol-binding protein, in multiple lung cells of IPF, and its correlation with the decline in lung function.
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影响因子:
3
作者:
Langfelder P;Horvath S
通讯作者:
Horvath S
影响因子:
4.3
作者:
Langfelder P;Luo R;Oldham MC;Horvath S
通讯作者:
Horvath S
影响因子:
14.9
作者:
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者:
Parkinson, Helen
DOI:
10.1165/rcmb.2013-0310oc
发表时间:
2015-02-01
影响因子:
6.4
作者:
Bauer, Yasmina;Tedrow, John;Kaminski, Naftali
通讯作者:
Kaminski, Naftali
影响因子:
4.3
作者:
Horvath, Steve;Dong, Jun
通讯作者:
Dong, Jun