Fig. 2

Selection of candidate target genes expressed under epigenetic regulation. Pipeline indicating the criteria followed for the selection of candidates: 1. Identification of the genes differentially expressed in the four paired cisplatin-sensitive and cisplatin-resistant cell lines A2780S/R and OVCAR3S/R that were consistent with those identified in the 123 patients interrogated in the TCGA with the same pathology and methodology (expression arrays). 2. We subsequently observed which genes coincided with those identified in the cell lines subjected to epigenetic reactivation treatment and that contained CpGs islands in the promoter regions. 3. From these, we selected those represented among the genes identified as differentially methylated in the global epigenome analysis (WGBS) conducted between the cisplatin-sensitive and cisplatin-resistant lines (4097 genes). These 29 candidates showed promoter hypermethylation as a consequence of cisplatin treatment and might therefore be involved in the onset of resistance in our in vitro model. These candidates were therefore selected by our pipeline for further screening based on the genomic location of methylated areas and the degree of methylation exhibited. This analysis was supported by external resources such as the Ensembl API, the Encyclopedia of DNA Elements (ENCODE) and patient biological data stored in TCGA