Computational protocol: The Use of Functional Chemical-Protein Associations to Identify Multi-Pathway Renoprotectants

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Protocol publication

[…] In this study, chemicals that are associated with multiple proteins (n≥10) were retrieved from the STITCH 3.1 database. A confidence score of 0.900 was selected as the threshold . All chemical-protein associations were imported into Cytoscape for data storage and topological analysis. The number of associated proteins was calculated for each chemical. Subsequently, each chemical was investigated to determine which signaling pathway with its associated proteins would be most significantly affected. This was accomplished by uploading their official gene symbol names onto the online functional annotation tool of DAVID . Homo sapiens was selected as the species background and the “KEGG_pathway” annotation was chosen. Over-represented regulation on a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was considered statistically significant only if Benjamini-adjusted p<0.05 . The parameter PW for each chemical was calculated as the number of significantly over-represented KEGG pathways affected, divided by the number of the associated proteins. A high PW value indicates that a given chemical is efficient in intervening signaling pathways as much as possible by virtue of a limited number of targets. To investigate whether the affected pathways were nephropathy-related, the Gene Prospector online tool in HuGE Navigator was applied to find literature-reported nephropathy-related genes . The online functional annotation tool of DAVID was then used to identify nephropathy-related pathways. […]

Pipeline specifications

Software tools DAVID, Gene Prospector
Databases HuGE Navigator KEGG KEGG PATHWAY
Application GWAS
Organisms Homo sapiens
Diseases Kidney Diseases
Chemicals Chlorophyll, Curcumin, Heme