Identification of Novel Genes and Biological Pathways That Overlap in Infectious and Nonallergic Diseases of the Upper and Lower Airways Using Network Analyses

In this report, we compared [1] pathways identified from network analysis using genes derived from published genome-wide family-based and association studies for otitis media, sinusitis, and lung phenotypes, to [2] pathways identified using differentially expressed genes from RNA-sequence data from lower airway, sinus, and middle ear tissues, in particular cholesteatoma tissue compared to middle ear mucosa. For otitis media, a large number of genes (n = 1,806) were identified as differentially expressed between cholesteatoma and middle ear mucosa, which in turn led to the identification of 68 pathways that are enriched in cholesteatoma. Two differentially expressed genes CR1 and SAA1 overlap in middle ear, sinus, and lower airway samples and are potentially novel genes for otitis media susceptibility. In addition, 56 genes were differentially expressed in both tissues from the middle ear and either sinus or lower airways. Pathways that are common in upper and lower airway diseases, whether from published DNA studies or from our RNA-sequencing analyses, include chromatin organization/remodeling, endocytosis, immune system process, protein folding, and viral process. Taken together, our findings from genetic susceptibility and differential tissue expression studies support the hypothesis that the unified airway theory wherein the upper and lower respiratory tracts act as an integrated unit also applies to infectious and nonallergic airway epithelial disease. Our results may be ...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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