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How cytokines co-occur across asthma patients: from bipartite network analysis to a molecular-based classification.

ABSTRACT: Asthmatic patients are currently classified as either severe or non-severe based primarily on their response to glucocorticoids. However, because this classification is based on a post-hoc assessment of treatment response, it does not inform the rational staging of disease or therapy. Recent studies in other diseases suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. We therefore measured cytokine values in bronchoalveolar lavage (BAL) samples of the lower respiratory tract obtained from 83 asthma patients, and used bipartite network visualizations with associated quantitative measures to conduct an exploratory analysis of the co-occurrence of cytokines across patients. The analysis helped to identify three clusters of patients which had a complex but understandable interaction with three clusters of cytokines, leading to insights for a state-based classification of asthma patients. Furthermore, while the patient clusters were significantly different based on key pulmonary functions, they appeared to have no significant relationship to the current classification of asthma patients. These results suggest the need to define a molecular-based classification of asthma patients, which could improve the diagnosis and treatment of this disease.

SUBMITTER: Bhavnani SK

PROVIDER: S-EPMC3277832 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

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How cytokines co-occur across asthma patients: from bipartite network analysis to a molecular-based classification.

Bhavnani Suresh K SK Victor Sundar S Calhoun William J WJ Busse William W WW Bleecker Eugene E Castro Mario M Ju Hyunsu H Pillai Regina R Oezguen Numan N Bellala Gowtham G Brasier Allan R AR

Journal of biomedical informatics 20111001

Asthmatic patients are currently classified as either severe or non-severe based primarily on their response to glucocorticoids. However, because this classification is based on a post-hoc assessment of treatment response, it does not inform the rational staging of disease or therapy. Recent studies in other diseases suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. We therefore measured cytokine values ...[more]

PMID: 21986291

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Project description:Bladder cancer (BC) is one of the most important cancers worldwide, and if it is diagnosed early, its progression in humans can be prevented and long-term survival will be achieved accordingly. This study aimed to identify novel micro-RNA (miRNA) and gene-based biomarkers for diagnosing BC. The microarray dataset of BC tissues (GSE13507) listed in the GEO database was analyzed for this purpose. The gene expression data from three BC tissues including 165 primary bladder cancer (PBC), 58 normal looking-bladder mucosae surrounding cancer (NBMSC), and 23 recurrent non-muscle invasive tumor tissues (RNIT) were used to reconstruct gene co-expression networks. After preprocessing and normalization, deferentially expressed genes (DEGs) were obtained and used to construct the weighted gene co-expression network (WGCNA). Gene co-expression modules and low-preserved modules were extracted among BC tissues using network clustering. Next, the experimentally validated mRNA-miRNA interaction information were used to reconstruct three mRNA-miRNA bipartite networks. Reactome pathway database and Gene ontology (GO) was subsequently performed for the extracted genes of three bipartite networks and miRNAs, respectively. To further analyze the data, ten hub miRNAs (miRNAs with the highest degree) were selected in each bipartite network to reconstruct three bipartite subnetworks. Finally, the obtained biomarkers were comprehensively investigated and discussed in authentic studies. The obtained results from our study indicated a group of genes including PPARD, CST4, CSNK1E, PTPN14, ETV6, and ADRM1 as well as novel miRNAs (e.g., miR-16-5p, miR-335-5p, miR-124-3p, and let-7b-5p) which might be potentially associated with BC and could be a potential biomarker. Afterward, three drug-gene interaction networks were reconstructed to explore candidate drugs for the treatment of BC. The hub miRNAs in the mRNA-miRNA bipartite network played a fundamental role in BC progression; however, these findings need further investigation.

Project description:BackgroundAsthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions.ObjectiveTo investigate inflammatory cytokines, lung function, sickness behaviour and asthma-related quality of life as determinants of self-rated health in patients with asthma, and to investigate if these variables co-vary over time.MethodsPlasma cytokines (IL-5, IL-6), lung function (FEV1), sickness behaviour, asthma-related quality of life and self-rated health were assessed in 181 patients with allergic asthma aged 18-64 years in a one-year longitudinal study. Mixed effect regression models and Spearman's correlation were performed to analyse the associations between repeated measurements.ResultsMore sickness behaviour and poorer asthma-related quality of life were associated with poorer self-rated health (p's<0.001). In men, both low and high levels of interleukin (IL)-6 and poorer lung function were related with poorer self-rated health (p's<0.05). Over the year, improved asthma-related quality of life was associated with better self-rated health (Spearman's rho = -0.34 women,-0.36 men, p's<0.01). Further, if sickness behaviour decreased, self-rated health improved, but only in women (Rho = -0.21, p<0.05). Increased FEV1 in men was associated with an increase in IL-6 (Rho = 0.24, p<0.05) as well as improved self-rated health (Rho = -0.21, p<0.05) and asthma-related quality of life (Rho = 0.29, p<0.01) over the year.ConclusionThe study highlights the importance of subjectively perceived sickness behaviour and asthma-related quality of life together with lung function as determinants of self-rated health in asthmatic patients. The importance of inflammatory activation for patient reported outcomes in chronic inflammatory conditions need further investigation.

Dataset Information

How cytokines co-occur across asthma patients: from bipartite network analysis to a molecular-based classification.

Publications

How cytokines co-occur across asthma patients: from bipartite network analysis to a molecular-based classification.

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