Epithelial structure maintenance

Abstract: Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group. Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients. We considered the top 708 SNPs, using a p-value cutoff of 5 × 10− 5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through a literature search, 7 out of the 8 gene products were found to be implicated in both pulmonary and cardiac diseases. Gene ontology and PPI analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.

Abstract: Background: Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group. Methods: Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients. Results: We considered the top 708 SNPs, using a p-value cutoff of 5x10-5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top-ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through literature search, 7 out of the 8 genes were found to be implicated in both pulmonary and cardiac diseases. Conclusion: Gene ontology and protein-protein interaction analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients.

Abstract: Module-based network analysis of diverse pharmacological mechanisms is critical to systematically understand combination therapies and disease outcomes. We first constructed drug-target ischemic networks in baicalin, jasminoidin, ursodeoxycholic acid, and their combinations baicalin and jasminoidin as well as jasminoidin and ursodeoxycholic acid groups and identified modules using the entropy-based clustering algorithm. The modules 11, 7, 4, 8 and 3 were identified as baicalin, jasminoidin, ursodeoxycholic acid, baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid-emerged responsive modules, while 12, 8, 15, 17 and 9 were identified as disappeared responsive modules based on variation of topological similarity, respectively. No overlapping differential biological processes were enriched between baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid pure emerged responsive modules, but two were enriched by their co-disappeared responsive modules including nucleotide-excision repair and epithelial structure maintenance. We found an additive effect of baicalin and jasminoidin in a divergent pattern and a synergistic effect of jasminoidin and ursodeoxycholic acid in a convergent pattern on "central hit strategy" of regulating inflammation against cerebral ischemia. The proposed module-based approach may provide us a holistic view to understand multiple pharmacological mechanisms associated with differential phenotypes from the standpoint of modular pharmacology.