Dataset Information

Delineation of a gene network underlying the pulmonary response to oxidative stress in asthma.

ABSTRACT: Cigarette smoke exposure induces a respiratory epithelial response that is mediated in part by oxidative stress. The contribution of oxidative stress to cigarette smoke-induced responses in asthmatic respiratory epithelium is not well understood. We sought to increase this understanding by employing data integration and systems biology approaches to publicly available microarray data deposited over the last several years. In this study, we analyzed 14 publicly available asthma- or tobacco-relevant data series and found 4 (2 mice and 2 human) that fulfilled adequate signal/noise thresholds using unsupervised clustering and F test statistics. Using significance filters and a 4-way Venn diagram approach, we identified 26 overlapping genes in the epithelial transcriptional stress response to cigarette smoke and asthma. This test set corresponded to a 26-member gene/protein network containing 18 members that were highly regulated in a fifth data series of direct lung oxidative stress. Of those network members, 2 stood out (ie, tissue inhibitor of metalloproteinase 1 and thrombospondin 1) owing to central location within the network and marked up-regulation sustained at later times in response to oxidative stress. These analyses identified key relationships and primary hypothetical targets for future studies of cigarette smoke-induced oxidative stress in asthma.

SUBMITTER: Freishtat RJ

PROVIDER: S-EPMC3328512 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Delineation of a gene network underlying the pulmonary response to oxidative stress in asthma.

Freishtat Robert J RJ Benton Angela S AS Watson Alan M AM Wang Zuyi Z Rose Mary C MC Hoffman Eric P EP

Journal of investigative medicine : the official publication of the American Federation for Clinical Research 20091001 7

Cigarette smoke exposure induces a respiratory epithelial response that is mediated in part by oxidative stress. The contribution of oxidative stress to cigarette smoke-induced responses in asthmatic respiratory epithelium is not well understood. We sought to increase this understanding by employing data integration and systems biology approaches to publicly available microarray data deposited over the last several years. In this study, we analyzed 14 publicly available asthma- or tobacco-releva ...[more]

PMID: 19730131

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Project description:BackgroundThe prevalence of diabetes is increasing worldwide. It has been long known that increased rates of inflammatory diseases, such as obesity (OBS), hypertension (HT) and cardiovascular diseases (CVD) are highly associated with type 2 diabetes (T2D). T2D and/or OBS can develop independently, due to genetic, behavioral or lifestyle-related variables but both lead to oxidative stress generation. The underlying mechanisms by which theses complications arise and manifest together remain poorly understood. Protein-protein interactions regulate nearly every living process. Availability of high-throughput genomic data has enabled unprecedented views of gene and protein co-expression, co-regulations and interactions in cellular systems.MethodsThe present work, applied a systems biology approach to develop gene interaction network models, comprised of high throughput genomic and PPI data for T2D. The genes differentially regulated through T2D were 'mined' and their 'wirings' were studied to get a more complete understanding of the overall gene network topology and their role in disease progression.ResultsBy analyzing the genes related to T2D, HT and OBS, a highly regulated gene-disease integrated network model has been developed that provides useful functional linkages among groups of genes and thus addressing how different inflammatory diseases are connected and propagated at genetic level. Based on the investigations around the 'hubs' that provided more meaningful insights about the cross-talk within gene-disease networks in terms of disease phenotype association with oxidative stress and inflammation, a hypothetical co-regulation disease mechanism model been proposed. The results from this study revealed that the oxidative stress mediated regulation cascade is the common mechanistic link among the pathogenesis of T2D, HT and other inflammatory diseases such as OBS.ConclusionThe findings provide a novel comprehensive approach for understanding the pathogenesis of various co-associated chronic inflammatory diseases by combining the power of pathway analysis with gene regulatory network evaluation.

Dataset Information

Delineation of a gene network underlying the pulmonary response to oxidative stress in asthma.

Publications

Delineation of a gene network underlying the pulmonary response to oxidative stress in asthma.

Similar Datasets

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