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Fig. 2 | Genome Medicine

Fig. 2

From: Integrated proteotranscriptomics of breast cancer reveals globally increased protein-mRNA concordance associated with subtypes and survival

Fig. 2

Pathway association of differentially expressed proteins and transcripts. a Enrichment of differentially expressed proteins between tumors and adjacent non-cancerous tissue (n = 2643; 2165 upregulated and 478 downregulated tumor proteins) in KEGG pathways. Enriched pathways at ≤ 10% FDR are shown for two categories, proteins upregulated (red) and downregulated (green) in tumors. The red and green bars highlight the pathways with enrichment for proteins without a similar enrichment for differentially expressed mRNAs. The gray bars indicate those pathways that were enriched for both proteins and mRNA in tumors. Several metabolism pathways, such as the pentose phosphate pathway, starch and sucrose metabolism, gluconeogenesis and glycolysis, galactose metabolism, and glutathione metabolism, were only enriched for upregulated proteins in tumors but not upregulated mRNAs. Four other pathways, TCA cycle, gap junction, pyruvate metabolism, and long-term depression, showed enrichment for proteins upregulated in tumors whereas pathway-associated mRNAs tended to be downregulated in these same tumors (green-bordered bars). For analysis, all proteins were ranked using Wald statistic and imported into the GSEA pre-ranked module. The KEGG gene sets of MSigDB were selected as the reference database. b Heatmap showing subtype-specific enrichment of proteins in KEGG BRITE categories and pathways. Hierarchical clustering using the pathway enrichment scores [FDR-based] yielded three branches with differential enrichment of proteins in KEGG pathways by breast cancer molecular subtype (luminal A, HER2-positive, ER-negative, triple-negative, and basal-like). Shown are unique and common features between subtypes. Red indicates upregulated proteins that are significantly enriched in pathways, whereas blue indicates downregulated proteins with pathway enrichment

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