Comprehensive Bioinformatics Analysis of Nobiletin

Data collection and processingCytotoxicity and mRNA arrays data were obtained from the NCI 60 DTP website (http.dtp.nci.nih.gov) (Monks et al., 1997). COMPARE analysis with the public library produces a list of drugs that have similarities with nobiletin, as well as a list of gene expressions on the NCI 60 cell line panel (Mahmoud et al., 2018). The similarity pattern is expressed as the Pearson correlation coefficient. In this study, the list of compounds and genes was limited to the Pearson correlation coefficient <-0.5 and> 0.5.
Functional and pathway enrichment analysisGene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out by The Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 (Huang da et al., 2009), with p<0.05 was selected as the cutoff value. Moreover, pathway enrichment was also conducted busing Overrepresentation Enrichment Analysis (ORA) from WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) with FDR<0.05 was selected as the cutoff value (Wang et al., 2017a).
Construction of PPI network and module analysisProtein-protein interaction (PPI) network was constructed with STRING-DB v11.0 (Szklarczyk et al., 2015). Confidence scores >0.7 were considered significant. PPI network was visualized by Cytoscape software. Genes with a degree score more than 5, analyzed by CytoHubba plugin, were selected as hub genes.