Cargando…
Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease
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...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141193/ https://www.ncbi.nlm.nih.gov/pubmed/35628257 http://dx.doi.org/10.3390/ijms23105447 |
_version_ | 1784715285022900224 |
---|---|
author | Ghandikota, Sudhir Sharma, Mihika Ediga, Harshavardhana H. Madala, Satish K. Jegga, Anil G. |
author_facet | Ghandikota, Sudhir Sharma, Mihika Ediga, Harshavardhana H. Madala, Satish K. Jegga, Anil G. |
author_sort | Ghandikota, Sudhir |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9141193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91411932022-05-28 Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease Ghandikota, Sudhir Sharma, Mihika Ediga, Harshavardhana H. Madala, Satish K. Jegga, Anil G. Int J Mol Sci Article 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. MDPI 2022-05-13 /pmc/articles/PMC9141193/ /pubmed/35628257 http://dx.doi.org/10.3390/ijms23105447 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ghandikota, Sudhir Sharma, Mihika Ediga, Harshavardhana H. Madala, Satish K. Jegga, Anil G. Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease |
title | Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease |
title_full | Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease |
title_fullStr | Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease |
title_full_unstemmed | Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease |
title_short | Consensus Gene Co-Expression Network Analysis Identifies Novel Genes Associated with Severity of Fibrotic Lung Disease |
title_sort | consensus gene co-expression network analysis identifies novel genes associated with severity of fibrotic lung disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141193/ https://www.ncbi.nlm.nih.gov/pubmed/35628257 http://dx.doi.org/10.3390/ijms23105447 |
work_keys_str_mv | AT ghandikotasudhir consensusgenecoexpressionnetworkanalysisidentifiesnovelgenesassociatedwithseverityoffibroticlungdisease AT sharmamihika consensusgenecoexpressionnetworkanalysisidentifiesnovelgenesassociatedwithseverityoffibroticlungdisease AT edigaharshavardhanah consensusgenecoexpressionnetworkanalysisidentifiesnovelgenesassociatedwithseverityoffibroticlungdisease AT madalasatishk consensusgenecoexpressionnetworkanalysisidentifiesnovelgenesassociatedwithseverityoffibroticlungdisease AT jeggaanilg consensusgenecoexpressionnetworkanalysisidentifiesnovelgenesassociatedwithseverityoffibroticlungdisease |