Fig. 2

Transcriptomics and proteomics druggability analysis generated a list of new potential protein targets for TNBC. a 3D correlation plot between FC of DE genes. Dark gray in 2D projections represents upregulated genes. Unifying DE genes exhibiting an FDR ≤ 0.05 and an FC ≥ +2; FDR ≤ 0.05 and FC ≤ −2; or an FDR > 0.05 are shown as purple, orange and green circles, respectively. b Venn diagrams showing that 134 genes (B, left) were equally downregulated, while 243 (b, right) were equally upregulated in all three comparisons. c Probes covering CpG islands were related to genes based on TSS proximity and their methylation status (values for different probes were averaged) were correlated to the gene expression FC (TNBC x Non-TNBC). d Circos plot comparing CpG islands methylation FC (green or pink lines) with gene expression FC (blue line) in the TNBC x Non-TNBC (outer circle) or TNBC x normal (inner circle) (chromosome ideogram denoted in the most outer circle). Values for both methylation and gene expression FC were averaged within every 5 Mbp. FC opposite spikes indicate that the higher the methylation FC, the lower the gene expression FC of the associated region, and vice-verse. e Protein level FC (MS dataset [64] performed with the same BRCA samples used in this work) and gene expression FC correlation in the comparison TNBC x Non-TNBC. f Pipeline used for new protein targets discovering. g Number of genes found in two or more publications (25) or in 0 or 1 publication (218) following the PubMed query “gene name + triple-negative breast cancer”. The genes that were non-cited or were cited only once were then evaluated in canSAR as either having available protein structure (67) or not (151), followed by a cutoff of being structurally druggable (42) or not (25). Among the 42 genes with a druggable structure, the top 10 based on the ligand-based druggability percentile are listed