Asthma Bridge: The Asthma Biorepository For Integrative Genomic Exploration

Raby, Benjamin A.; Barnes, Kathleen C.; Beaty, Terri H.; Bosco, Anthony; Carey, Vincent J.; Castro, Mario; Cheadle, Chris; Gilliland, Frank D.; Islam, Kamrul; Salam, Muhammad T.; Kelly, Roxanne; Klanderman, Barbara J.; Lemanske, Robert; Guilbert, Theresa W.; London, Stephanie J.; Liu, Andy; Martínez, Fernando J.; Mathias, Rasika A.; Nicolae, Dan L.; Ober, Carole; Qiu, Weiliang; Solway, Julian; Strunk, Robert C.; Sylvia, Jody M.; Tubbs, Diana; Weiss, Scott T.

doi:10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a6189

Cited by 9 publications

(12 citation statements)

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“…To address these deficiencies and determine the transcriptomic bases of chronic and acute asthma control, we performed a large-scale gene expressionphenotype association analysis of 1,170 adults with asthma ( Figure 1), consisting of four nonoverlapping cohorts from Asthma BRIDGE (Asthma BioRepository for Integrative Genomic Exploration) (9) and the CAMP (Childhood Asthma Management Program) study (10). Asthma control was assessed using modified forms of the validated Asthma Control Test (ACT), a composite clinical measure of asthma symptom control (11).…”

Section: Discussionmentioning

confidence: 99%

“…The Asthma BRIDGE dataset, which has been described previously (9,14,15), comprises a cohort of subjects selected from the EVE asthma genetics consortium (16). Additional detail on subject ascertainment is presented in the METHODS section of the online supplement.…”

Section: Methodsmentioning

confidence: 99%

“…Using clinical phenotype data available in Asthma BRIDGE and in CAMP, we developed two composite scores summarizing self-reported asthma control in the preceding 6 months (chronic, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 7 days (acute, 0-28), respectively, each modeled on the ACT questionnaire (11), where higher scores indicate worse asthma control. Based on the medians of the corresponding phenotypic distributions, optimal chronic asthma control was defined as a score less than or equal to six in BRIDGE WB and moderately suboptimal asthma control was defined as a score less than or equal to 11 in BRIDGE CD4 ( Figure 2).…”

Section: Methodsmentioning

confidence: 99%

“…Subjects were typed on either the HumanHT-12 v4 Expression or HumanRef8 v2 BeadChip platforms (Illumina, Inc., San Diego, CA) (9,18). Log 2 -transformed and quantile-normalized data that passed stringent and commonly used quality control metrics were available for 10,456 gene expression probes found across BRIDGE WB, BRIDGE CD4, and CAMP WB and for a further subset of 6,555 probes in CAMP CD4.…”

Section: Methodsmentioning

confidence: 99%

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Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Croteau‐Chonka¹,

Qiu²,

Martínez

et al. 2017

Am J Respir Crit Care Med

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Rationale: Maintaining optimal symptom control remains the primary objective of asthma treatment. Better understanding of the biologic underpinnings of asthma control may lead to the development of improved clinical and pharmaceutical approaches.Objectives: To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control.Methods: We performed gene set enrichment analyses of asthma control in 1,170 adults with asthma, each with gene expression data derived from either whole blood (WB) or unstimulated CD4 1 T lymphocytes (CD4), and a self-reported asthma control score representing either the preceding 6 months (chronic) or 7 days (acute). Our study comprised a discovery WB cohort (n = 245, chronic) and three independent, nonoverlapping replication cohorts: a second WB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute). Measurements and Main Results:In the WB discovery cohort, we found significant overrepresentation of genes associated with asthma control in 1,106 gene sets from the Molecular Signatures Database (false discovery rate, ,5%). Of these, 583 (53%) replicated in at least one replication cohort (false discovery rate, ,25%). Suboptimal control was associated with signatures of eosinophilic and granulocytic inflammatory signals, whereas optimal control signatures were enriched for immature lymphocytic patterns. These signatures included two related biologic processes related to activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and lipopolysaccharide. Conclusions:Together, these results demonstrate the existence of specific, reproducible transcriptomic components in blood that vary with degree of asthma control and implicate a novel biologic target (TREM-1).

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Croteau‐Chonka¹,

Qiu²,

Martínez

et al. 2017

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

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“…This classifier was applied to 870 whole blood samples selected from the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE) (24,25). Cross-platform replication of the TEA cluster clinical phenotypes was conducted (24,25).…”

Section: Validation Studiesmentioning

confidence: 99%

Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma

Yan

Chu

Gómez

et al. 2015

Am J Respir Crit Care Med

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102

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Rationale: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.Objectives: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.Methods: Gene expression in the sputum and blood of patients with asthma was measured using Affymetrix microarrays. Unsupervised clustering analysis based on pathways from the Kyoto Encyclopedia of Genes and Genomes was used to identify TEA clusters. Logistic regression analysis of matched blood samples defined an expression profile in the circulation to determine the TEA cluster assignment in a cohort of children with asthma to replicate clinical phenotypes.Measurements and Main Results: Three TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower prebronchodilator FEV 1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04) compared with the other TEA clusters. TEA cluster 2, the smallest cluster, had the most subjects that were hospitalized for asthma (P = 0.04). TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 3 10 26) and hospitalization (P = 0.01), respectively.Conclusions: There are common patterns of gene expression in the sputum and blood of children and adults that are associated with near-fatal, severe, and milder asthma.

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Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

Mirzakhani

Krause

et al. 2021

iScience

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Summary RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung.

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Asthma Bridge: The Asthma Biorepository For Integrative Genomic Exploration

Cited by 9 publications

References 0 publications

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

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