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10.1164/rccm.201406-1099OC http://scihub22266oqcxt.onion/10.1164/rccm.201406-1099OC C4294630!4294630 !25338189     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25338189 &cmd=llinks): Failed to open stream: HTTP request failed! 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Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways |pdf=|usr=}}{{25338189 }} gab.com Text Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways JO: Am J Respir Crit Care Med http://www.kidney.de/pget.php?&tw=1&pmid=25338189 #FOAvip RATIONALE: Although asthma is recognized as a heterogeneous disease associated with clinical phenotypes, the molecular basis of these phenotypes remains poorly understood. Although genomic studies have successfully broadened our understanding in diseases such as cancer, they have not been widely used in asthma studies. OBJECTIVES: To link gene expression patterns to clinical asthma phenotypes. METHODS: We used a microarray platform to analyze bronchial airway epithelial cell gene expression in relation to the asthma biomarker fractional exhaled nitric oxide (FeNO) in 155 subjects with asthma and healthy control subjects from the Severe Asthma Research Program (SARP). MEASUREMENTS AND MAIN RESULTS: We first identified a diverse set of 549 genes whose expression correlated with FeNO. We used k-means to cluster the patient samples according to the expression of these genes, identifying five asthma clusters/phenotypes with distinct clinical, physiological, cellular, and gene transcription characteristics-termed "subject clusters" (SCs). To then investigate differences in gene expression between SCs, a total of 1,384 genes were identified that highly differentiated the SCs at an unadjusted P value < 10(-6). Hierarchical clustering of these 1,384 genes identified nine gene clusters or "biclusters," whose coexpression suggested biological characteristics unique to each SC. Although genes related to type 2 inflammation were present, novel pathways, including those related to neuronal function, WNT pathways, and actin cytoskeleton, were noted. CONCLUSIONS: These findings show that bronchial epithelial cell gene expression, as related to the asthma biomarker FeNO, can identify distinct asthma phenotypes, while also suggesting the presence of underlying novel gene pathways relevant to these phenotypes. Twit Text FOAVip Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways ????Am J Respir Crit Care Med http://www.kidney.de/pget.php?&tw=1&pmid=25338189 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25338189 #FOAvip English Wikipedia <ref>{{Cite pmid|25338189 }}</ref> Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways #MMPMID25338189 Modena BD ; Tedrow JR ; Milosevic J ; Bleecker ER ; Meyers DA ; Wu W ; Bar-Joseph Z ; Erzurum SC ; Gaston BM ; Busse WW ; Jarjour NN ; Kaminski N ; Wenzel SE Am J Respir Crit Care Med 2014[Dec]; 190 (12 ): 1363-72 PMID25338189 show ga RATIONALE: Although asthma is recognized as a heterogeneous disease associated with clinical phenotypes, the molecular basis of these phenotypes remains poorly understood. Although genomic studies have successfully broadened our understanding in diseases such as cancer, they have not been widely used in asthma studies. OBJECTIVES: To link gene expression patterns to clinical asthma phenotypes. METHODS: We used a microarray platform to analyze bronchial airway epithelial cell gene expression in relation to the asthma biomarker fractional exhaled nitric oxide (FeNO) in 155 subjects with asthma and healthy control subjects from the Severe Asthma Research Program (SARP). MEASUREMENTS AND MAIN RESULTS: We first identified a diverse set of 549 genes whose expression correlated with FeNO. We used k-means to cluster the patient samples according to the expression of these genes, identifying five asthma clusters/phenotypes with distinct clinical, physiological, cellular, and gene transcription characteristics-termed "subject clusters" (SCs). To then investigate differences in gene expression between SCs, a total of 1,384 genes were identified that highly differentiated the SCs at an unadjusted P value < 10(-6). Hierarchical clustering of these 1,384 genes identified nine gene clusters or "biclusters," whose coexpression suggested biological characteristics unique to each SC. Although genes related to type 2 inflammation were present, novel pathways, including those related to neuronal function, WNT pathways, and actin cytoskeleton, were noted. CONCLUSIONS: These findings show that bronchial epithelial cell gene expression, as related to the asthma biomarker FeNO, can identify distinct asthma phenotypes, while also suggesting the presence of underlying novel gene pathways relevant to these phenotypes. |Adult [MESH] |Asthma/*genetics/metabolism [MESH] |Biomarkers [MESH] |Bronchi/cytology/metabolism [MESH] |Case-Control Studies [MESH] |Female [MESH] |Gene Expression/*genetics [MESH] |Humans [MESH] |Male [MESH] |Middle Aged [MESH] |Multigene Family/genetics [MESH] |Nitric Oxide/*metabolism [MESH] |Oligonucleotide Array Sequence Analysis [MESH] |Phenotype [MESH]Gene expression in relation to exhaled nitric oxide identifies novel a(epmc).pdf DeepDyve Pubget Overpricing