{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:31:22Z","timestamp":1793046682764,"version":"4.5.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>An integrative analysis focused on multi-tissue transcriptomics has not been done for asthma. Tissue-specific DEGs remain undetected in many multi-tissue analyses, which influences identification of disease-relevant pathways and potential drug candidates. Transcriptome data from 609 cases and 196 controls, generated using airway epithelium, bronchial, nasal, airway macrophages, distal lung fibroblasts, proximal lung fibroblasts, CD4+ lymphocytes, CD8+ lymphocytes from whole blood and induced sputum samples, were retrieved from Gene Expression Omnibus (GEO). Differentially regulated asthma-relevant genes identified from each sample type were used to identify (a) tissue-specific and tissue\u2013shared asthma pathways, (b) their connection to GWAS-identified disease genes to identify candidate tissue for functional studies, (c) to select surrogate sample for invasive tissues, and finally (d) to identify potential drug candidates via connectivity map analysis. We found that inter-tissue similarity in gene expression was more pronounced at pathway\/functional level than at gene level with highest similarity between bronchial epithelial cells and lung fibroblasts, and lowest between airway epithelium and whole blood samples. Although public-domain gene expression data are limited by inadequately annotated per-sample demographic and clinical information which limited the analysis, our tissue-resolved analysis clearly demonstrated relative importance of unique and shared asthma pathways, At the pathway level, IL-1b signaling and ERK signaling were significant in many tissue types, while Insulin-like growth factor and TGF-beta signaling were relevant in only airway epithelial tissue. IL-12 (in macrophages) and Immunoglobulin signaling (in lymphocytes) and chemokines (in nasal epithelium) were the highest expressed pathways. Overall, the IL-1 signaling genes (inflammatory) were relevant in the airway compartment, while pro-Th2 genes including IL-13 and STAT6 were more relevant in fibroblasts, lymphocytes, macrophages and bronchial biopsies. These genes were also associated with asthma in the GWAS catalog. Support Vector Machine showed that DEGs based on macrophages and epithelial cells have the highest and lowest discriminatory accuracy, respectively. Drug (entinostat, BMS-345541) and genetic perturbagens (KLF6, BCL10, INFB1 and BAMBI) negatively connected to disease at multi-tissue level could potentially repurposed for treating asthma. Collectively, our study indicates that the DEGs, perturbagens and disease are connected differentially depending on tissue\/cell types. While most of the existing literature describes asthma transcriptome data from individual sample types, the present work demonstrates the utility of multi-tissue transcriptome data. Future studies should focus on collecting transcriptomic data from multiple tissues, age and race groups, genetic background, disease subtypes and on the availability of better-annotated data in the public domain.<\/jats:p>","DOI":"10.1534\/g3.120.401718","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T01:20:15Z","timestamp":1599614415000},"page":"4049-4062","source":"Crossref","is-referenced-by-count":18,"title":["The Utility of Resolving Asthma Molecular Signatures Using Tissue-Specific Transcriptome Data"],"prefix":"10.1093","volume":"10","author":[{"given":"Debajyoti","family":"Ghosh","sequence":"first","affiliation":[{"name":"Immunology and Allergy, Department of Internal Medicine, University of Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Epidemiology, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Immunology and Allergy, Department of Internal Medicine, University of Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tesfaye B","family":"Mersha","sequence":"additional","affiliation":[{"name":"Division of Asthma Research, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,1]]},"reference":[{"key":"2021042011184363000_bib1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1111\/cea.12879","article-title":"Mast cells are permissive for rhinovirus replication: potential implications for asthma exacerbations.","volume":"47","author":"Akoto","year":"2017","journal-title":"Clin. Exp. Allergy"},{"key":"2021042011184363000_bib2","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1016\/j.rmed.2014.08.008","article-title":"Transforming growth factor beta and severe asthma: a perfect storm.","volume":"108","author":"Al-Alawi","year":"2014","journal-title":"Respir. Med."},{"key":"2021042011184363000_bib3","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nrg3891","article-title":"The role of regulatory variation in complex traits and disease.","volume":"16","author":"Albert","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"2021042011184363000_bib4","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1002\/jcb.25536","article-title":"Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of beta1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.","volume":"117","author":"\u00c1lvarez-Santos","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"2021042011184363000_bib5","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2013update.","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2021042011184363000_bib6","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.jtemb.2017.08.011","article-title":"The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients.","volume":"44","author":"Besiktepe","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"2021042011184363000_bib7","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1164\/rccm.201706-1070OC","article-title":"IFN-stimulated Gene Expression, Type 2 Inflammation, and Endoplasmic Reticulum Stress in Asthma.","volume":"197","author":"Bhakta","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021042011184363000_bib8","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.jaci.2007.09.017","article-title":"Time for a paradigm shift in asthma treatment: from relieving bronchospasm to controlling systemic inflammation.","volume":"120","author":"Bjermer","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042011184363000_bib9","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/01902140902745174","article-title":"A comparison of two sets of microarray experiments to define allergic asthma expression pattern.","volume":"35","author":"Chamberland","year":"2009","journal-title":"Exp. Lung Res."},{"key":"2021042011184363000_bib10","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.molimm.2015.12.012","article-title":"MiR-23b controls TGF-beta1 induced airway smooth muscle cell proliferation via TGFbetaR2\/p-Smad3 signals.","volume":"70","author":"Chen","year":"2016","journal-title":"Mol. Immunol."},{"key":"2021042011184363000_bib11","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.4049\/jimmunol.1002568","article-title":"Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways.","volume":"186","author":"Choy","year":"2011","journal-title":"J. Immunol."},{"key":"2021042011184363000_bib12","doi-asserted-by":"publisher","first-page":"L545","DOI":"10.1152\/ajplung.2000.278.3.L545","article-title":"IGFBP-3 mediates TGF-beta1-induced cell growth in human airway smooth muscle cells.","volume":"278","author":"Cohen","year":"2000","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"2021042011184363000_bib13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/tpj.2013.5","article-title":"A genome-wide association study of bronchodilator response in asthmatics.","volume":"14","author":"Duan","year":"2014","journal-title":"Pharmacogenomics J."},{"key":"2021042011184363000_bib14","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2021042011184363000_bib15","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1186\/1471-2164-8-461","article-title":"Literature Lab: a method of automated literature interrogation to infer biology from microarray analysis.","volume":"8","author":"Febbo","year":"2007","journal-title":"BMC Genomics"},{"key":"2021042011184363000_bib16","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/ijc.26364","article-title":"Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.","volume":"131","author":"Fekete","year":"2012","journal-title":"Int. J. Cancer"},{"key":"2021042011184363000_bib17","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.ajhg.2018.04.002","article-title":"The Post-GWAS Era: From Association to Function.","volume":"102","author":"Gallagher","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"2021042011184363000_bib18","doi-asserted-by":"publisher","first-page":"442","DOI":"10.5551\/jat.ED017","article-title":"From Association to Function in the Post-GWAS Era.","volume":"22","author":"Gotoda","year":"2015","journal-title":"J. Atheroscler. Thromb."},{"key":"2021042011184363000_bib19","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1165\/rcmb.2010-0027TR","article-title":"Role of transforming growth factor-beta in airway remodeling in asthma.","volume":"44","author":"Halwani","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021042011184363000_bib20","doi-asserted-by":"publisher","first-page":"9362","DOI":"10.1073\/pnas.0903103106","article-title":"Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.","volume":"106","author":"Hindorff","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042011184363000_bib21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.","volume":"37","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2021042011184363000_bib22","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.","volume":"4","year":"2009","journal-title":"Nat. Protoc."},{"key":"2021042011184363000_bib23","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1164\/rccm.201009-1452OC","article-title":"Airway fibroblasts in asthma manifest an invasive phenotype.","volume":"183","author":"Ingram","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021042011184363000_bib24","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1164\/rccm.200907-1071OC","article-title":"Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium.","volume":"181","author":"Kicic","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021042011184363000_bib25","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1084\/jem.20051982","article-title":"The Bcl10-Malt1 complex segregates Fc epsilon RI-mediated nuclear factor kappa B activation and cytokine production from mast cell degranulation.","volume":"203","author":"Klemm","year":"2006","journal-title":"J. Exp. Med."},{"key":"2021042011184363000_bib26","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/mp.2015.226","article-title":"Understanding how non-coding genomic polymorphisms affect gene expression.","volume":"21","author":"Koester","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"2021042011184363000_bib27","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1155\/2008\/202615","article-title":"Quality of bronchial biopsies for morphology study and cell sampling: a comparison of asthmatic and healthy subjects.","volume":"15","author":"Labont\u00e9","year":"2008","journal-title":"Can. Respir. J."},{"key":"2021042011184363000_bib28","doi-asserted-by":"publisher","first-page":"20870","DOI":"10.1073\/pnas.0810772105","article-title":"A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes.","volume":"105","author":"Lage","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042011184363000_bib29","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","article-title":"The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.","volume":"313","author":"Lamb","year":"2006","journal-title":"Science"},{"key":"2021042011184363000_bib30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1471-2164-5-21","article-title":"Functional classes of bronchial mucosa genes that are differentially expressed in asthma.","volume":"5","author":"Laprise","year":"2004","journal-title":"BMC Genomics"},{"key":"2021042011184363000_bib31","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/nm1105","article-title":"Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung.","volume":"10","author":"Lee","year":"2004","journal-title":"Nat. Med."},{"key":"2021042011184363000_bib32","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1111\/bjd.12178","article-title":"Association of KIF3A, but not OVOL1 and ACTL9, with atopic eczema in Italian patients.","volume":"168","author":"Lepre","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"2021042011184363000_bib33","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1109\/TVCG.2014.2346248","article-title":"UpSet: Visualization of Intersecting Sets.","volume":"20","author":"Lex","year":"2014","journal-title":"IEEE Trans. Vis. Comput. Graph."},{"key":"2021042011184363000_bib34","doi-asserted-by":"publisher","first-page":"e0043","DOI":"10.1097\/MD.0000000000010043","article-title":"Genome-wide association study of maternal genetic effects and parent-of-origin effects on food allergy.","volume":"97","author":"Liu","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"2021042011184363000_bib35","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.humimm.2009.11.005","article-title":"Alveolar macrophages in allergic asthma: an expression signature characterized by heat shock protein pathways.","volume":"71","author":"Madore","year":"2010","journal-title":"Hum. Immunol."},{"key":"2021042011184363000_bib36","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.jaci.2006.07.026","article-title":"Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march.","volume":"118","author":"Marenholz","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042011184363000_bib37","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1165\/rcmb.2007-0325OC","article-title":"Nasal epithelial cells as surrogates for bronchial epithelial cells in airway inflammation studies.","volume":"39","author":"McDougall","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021042011184363000_bib38","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1186\/1743-422X-8-409","article-title":"Kruppel-like factor 6 regulates transforming growth factor-beta gene expression during human respiratory syncytial virus infection.","volume":"8","author":"Mgbemena","year":"2011","journal-title":"Virol. J."},{"key":"2021042011184363000_bib39","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1164\/rccm.201607-1407OC","article-title":"Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.","volume":"195","author":"Modena","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021042011184363000_bib40","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1164\/ajrccm.160.6.9903131","article-title":"Bronchoalveolar lavage fluid from asthmatic subjects is mitogenic for human airway smooth muscle.","volume":"160","author":"Naureckas","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021042011184363000_bib41","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1165\/ajrcmb.15.3.8810646","article-title":"Transforming growth factor beta 1 (TGF beta 1) gene expression by eosinophils in asthmatic airway inflammation.","volume":"15","author":"Ohno","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021042011184363000_bib42","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1038\/46794","article-title":"Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.","volume":"401","author":"Onichtchouk","year":"1999","journal-title":"Nature"},{"key":"2021042011184363000_bib43","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/1471-2105-10-62","article-title":"RankAggreg, an R package for weighted rank aggregation.","volume":"10","author":"Pihur","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2021042011184363000_bib44","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.jaci.2013.11.025","article-title":"Dissecting childhood asthma with nasal transcriptomics distinguishes subphenotypes of disease.","volume":"133","author":"Poole","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"2021042011184363000_bib45","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1165\/ajrcmb.18.6.3152","article-title":"Catalytic activation of extracellular signal-regulated kinases induces cyclin D1 expression in primary tracheal myocytes.","volume":"18","author":"Ramakrishnan","year":"1998","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021042011184363000_bib46","doi-asserted-by":"publisher","first-page":"8A","DOI":"10.1016\/j.chest.2019.02.028","article-title":"OVEREXPRESSION OF BCL10 IN SEVERE ASTHMATIC BRONCHIAL FIBROBLASTS.","volume":"155","author":"Ramakrishnan","year":"2019","journal-title":"Chest"},{"key":"2021042011184363000_bib47","doi-asserted-by":"publisher","first-page":"e184","DOI":"10.1371\/journal.pmed.0050184","article-title":"Key issues in conducting a meta-analysis of gene expression microarray datasets.","volume":"5","author":"Ramasamy","year":"2008","journal-title":"PLoS Med."},{"key":"2021042011184363000_bib48","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1039\/C4MB00328D","article-title":"Connecting gene expression data from connectivity map and in silico target predictions for small molecule mechanism-of-action analysis.","volume":"11","author":"Ravindranath","year":"2015","journal-title":"Mol. Biosyst."},{"key":"2021042011184363000_bib49","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1756-0381-1-8","article-title":"Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes.","volume":"1","author":"Reverter","year":"2008","journal-title":"BioData Min."},{"key":"2021042011184363000_bib50","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature14248","article-title":"Integrative analysis of 111 reference human epigenomes.","volume":"518","author":"Roadmap Epigenomics Consortium","year":"2015","journal-title":"Nature"},{"key":"2021042011184363000_bib51","doi-asserted-by":"publisher","first-page":"8658","DOI":"10.1038\/ncomms9658","article-title":"Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.","volume":"6","author":"Soler Artigas","year":"2015","journal-title":"Nat. Commun."},{"key":"2021042011184363000_bib52","doi-asserted-by":"publisher","first-page":"e64483","DOI":"10.1371\/journal.pone.0064483","article-title":"Identification of novel tissue-specific genes by analysis of microarray databases: a human and mouse model.","volume":"8","author":"Song","year":"2013","journal-title":"PLoS One"},{"key":"2021042011184363000_bib53","first-page":"1437","article-title":"A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.","volume-title":"Cell","author":"Subramanian","year":"2017"},{"key":"2021042011184363000_bib54","doi-asserted-by":"publisher","first-page":"1702173","DOI":"10.1183\/13993003.02173-2017","article-title":"Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis.","volume":"51","author":"Takahashi","year":"2018","journal-title":"Eur. Respir. J."},{"key":"2021042011184363000_bib55","doi-asserted-by":"publisher","first-page":"e85802","DOI":"10.1371\/journal.pone.0085802","article-title":"Nasal epithelial cells can act as a physiological surrogate for paediatric asthma studies.","volume":"9","author":"Thavagnanam","year":"2014","journal-title":"PLoS One"},{"key":"2021042011184363000_bib56","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1242\/dmm.030114","article-title":"Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis.","volume":"10","author":"Tjin","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"2021042011184363000_bib57","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/ng.888","article-title":"Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.","volume":"43","author":"Torgerson","year":"2011","journal-title":"Nat. Genet."},{"key":"2021042011184363000_bib58","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jaci.2011.08.011","article-title":"Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma.","volume":"129","author":"Tsitsiou","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042011184363000_bib59","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma.","volume":"25","author":"Vieira Braga","year":"2019","journal-title":"Nat. Med."},{"key":"2021042011184363000_bib60","article-title":"The deletion of Bambi attenuates experimental asthma in mice.","volume":"50","author":"Vock","year":"2017","journal-title":"Eur. Respir. J."},{"key":"2021042011184363000_bib61","doi-asserted-by":"publisher","author":"Vock","year":"2015","DOI":"10.1055\/s-0035-1548658"},{"key":"2021042011184363000_bib62","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1465-9921-15-9","article-title":"dsRNA-induced changes in gene expression profiles of primary nasal and bronchial epithelial cells from patients with asthma, rhinitis and controls.","volume":"15","author":"Wagener","year":"2014","journal-title":"Respir. Res."},{"key":"2021042011184363000_bib63","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/ng.3787","article-title":"Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.","volume":"49","author":"Wain","year":"2017","journal-title":"Nat. Genet."},{"key":"2021042011184363000_bib64","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1039\/C5MB00379B","article-title":"Dissecting Xuesaitong\u2019s mechanisms on preventing stroke based on the microarray and connectivity map.","volume":"11","author":"Wang","year":"2015","journal-title":"Mol. Biosyst."},{"key":"2021042011184363000_bib65","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-1-4939-8955-3_5","article-title":"Transcriptomic Data Mining and Repurposing for Computational Drug Discovery.","volume":"1903","author":"Wang","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"2021042011184363000_bib66","doi-asserted-by":"publisher","first-page":"31911","DOI":"10.1038\/srep31911","article-title":"TGF-beta\/BAMBI pathway dysfunction contributes to peripheral Th17\/Treg imbalance in chronic obstructive pulmonary disease.","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"2021042011184363000_bib67","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S1569-9048(03)00154-X","article-title":"Mitogenic signaling pathways in airway smooth muscle.","volume":"137","author":"Zhou","year":"2003","journal-title":"Respir. Physiol. Neurobiol."},{"key":"2021042011184363000_bib68","first-page":"1998","article-title":"BMS345541 inhibits airway inflammation and epithelialmesenchymal transition in airway remodeling of asthmatic mice.","volume":"42","author":"Zhu","year":"2018","journal-title":"Int. J. Mol. Med."}],"container-title":["G3 Genes|Genomes|Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/10\/11\/4049\/37192369\/g3journal4049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/g3journal\/article-pdf\/10\/11\/4049\/37192369\/g3journal4049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T14:05:20Z","timestamp":1618927520000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/g3journal\/article\/10\/11\/4049\/6048622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,1]]},"references-count":68,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1534\/g3.120.401718","relation":{},"ISSN":["2160-1836"],"issn-type":[{"value":"2160-1836","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,11,1]]},"published":{"date-parts":[[2020,11,1]]}}}