898:
Asthma associated transcriptomic profiles differ by tissue
Monday, March 5, 2018: 2:45 PM
S230EF (Convention Center)
Debajyoti Ghosh, PhD, , ,
RATIONALE: Gene-expression patterns in asthma show remarkable diversity across tissues. However, in most studies, differentially expressed genes across various tissues are analyzed together in an average profile framework. We hypothesize that there are tissue-specific as well as tissue-shared differentially expressed genes critical for asthma development. We expect that tissue-shared expression patterns could serve as a surrogate (e.g. nasal) biomarker for less accessible tissues (e.g. bronchial).

METHODS: We analyzed fourteen gene expression datasets from NCBI GEO database in relation to asthma across various tissues (e.g. blood, bronchial fibroblasts, alveolar macrophages, nasal epithelium, etc.). Differentially expressed asthma genes (DEAGs) for individual tissue were identified following a rank-based approach. Unique /shared DEAGs and their fold-change values were used to identify relevant pathways.

RESULTS: Little overlap in gene expression patterns across tissues were observed at the gene level compared to pathway/functional level. IL-1beta and ERK signaling pathways have been found to play a critical role in asthma manifestation in a wide range of tissue types whereas TGF-beta signaling is most relevant in airway epithelial tissue. Other relevant pathways are IL-12 (in macrophages), immunoglobulin signaling (in lymphocytes) and chemokine signaling (in nasal epithelium).

CONCLUSIONS: This analysis found both overlapping and unique pathways in different tissues that play important roles in asthma development. Tissue-specific DEAG signatures appear relevant for understanding the diverse tissue-specific patho-biology of asthma. The reported tissue-specific and shared gene signatures for asthma may provide the basis for developing novel asthma biomarkers and more selective asthma therapies.