Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease.
Sudhir GhandikotaMihika SharmaHarshavardhana H EdigaSatish K MadalaAnil G JeggaPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- lung function
- idiopathic pulmonary fibrosis
- network analysis
- genome wide
- cystic fibrosis
- chronic obstructive pulmonary disease
- air pollution
- copy number
- genome wide identification
- binding protein
- dna methylation
- poor prognosis
- extracellular matrix
- interstitial lung disease
- cell migration
- respiratory failure
- early onset
- single cell
- magnetic resonance
- systemic sclerosis
- multiple sclerosis
- big data
- genome wide analysis
- computed tomography
- induced apoptosis
- bone marrow
- mesenchymal stem cells
- stem cells
- machine learning
- transcription factor
- contrast enhanced
- cell proliferation
- magnetic resonance imaging
- cell therapy
- mechanical ventilation
- single molecule
- case control
- acute respiratory distress syndrome
- bone regeneration
- cell cycle arrest