Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods.
BMC Med Genomics
; 8: 1, 2015 Jan 13.
Article
en En
| MEDLINE
| ID: mdl-25582225
ABSTRACT
BACKGROUND:
Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.METHODS:
Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study. Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.RESULTS:
Individual genes were not found to be significantly associated with the number of exacerbations. However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association. A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection. Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections. The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.CONCLUSION:
A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness. While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biología Computacional
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Predisposición Genética a la Enfermedad
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Perfilación de la Expresión Génica
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Enfermedad Pulmonar Obstructiva Crónica
Tipo de estudio:
Clinical_trials
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
BMC Med Genomics
Asunto de la revista:
GENETICA MEDICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos