Sreekumar et al, 2009. E. D. B. A. C. Ben. PCa. Quantification of metabolite. Log2 (UDP-GlcNA c). Quantification of metabolite. Fold expression. Fold expression.
Autoimmune thyroid disease Arachidonic acid metabolism Renal cell carcinoma Synthesis and degradation of ketone bodies Oxidative phosphorylation Galactose metabolism Pyruvate metabolism Butanoate metabolism Linoleic acid metabolism Reductive carboxylate cycle (CO2 fixation) Methionine metabolism Phenylalanine metabolism Urea cycle and metabolism of amino groups Glutamate metabolism Epithelial cell signaling in Helicobacter pylori infection Pathways in cancer GnRH signaling pathway Parkinson's disease Valine, leucine and isoleucine degradation Pentose phosphate pathway Alanine and aspartate metabolism Pantothenate and CoA biosynthesis Benzoate degradation via CoA ligation Tryptophan metabolism Aminophosphonate metabolism Glyoxylate and dicarboxylate metabolism Glycerophospholipid metabolism beta−Alanine metabolism Propanoate metabolism Tyrosine metabolism Inositol phosphate metabolism Porphyrin and chlorophyll metabolism Sulfur metabolism Taurine and hypotaurine metabolism Methane metabolism Glycolysis / Gluconeogenesis Phenylalanine, tyrosine and tryptophan biosynthesis Biosynthesis of steroids Ether lipid metabolism Starch and sucrose metabolism Biosynthesis of unsaturated fatty acids Citrate cycle (TCA cycle) Glycerolipid metabolism C21−Steroid hormone metabolism Long−term depression Styrene degradation Caffeine metabolism Pentose and glucuronate interconversions Fc epsilon RI signaling pathway Sphingolipid metabolism gamma−Hexachlorocyclohexane degradation Glutathione metabolism Peptidoglycan biosynthesis Lysine biosynthesis Vitamin B6 metabolism Fructose and mannose metabolism Phosphatidylinositol signaling system Thiamine metabolism Hedgehog signaling pathway Taste transduction Bile acid biosynthesis Ascorbate and aldarate metabolism Huntington's disease Lysine degradation Glycine, serine and threonine metabolism Basal cell carcinoma Alkaloid biosynthesis II Arginine and proline metabolism Gap junction Long−term potentiation Nicotinate and nicotinamide metabolism Fatty acid biosynthesis Amyotrophic lateral sclerosis (ALS) D−Glutamine and D−glutamate metabolism Histidine metabolism Alkaloid biosynthesis I Aminoacyl−tRNA biosynthesis Pyrimidine metabolism Purine metabolism Cyanoamino acid metabolism Nitrogen metabolism Cysteine metabolism Valine, leucine and isoleucine biosynthesis Aminosugars metabolism Biotin metabolism Riboflavin metabolism
−log(0.03) −log(0.1)
0.05 −log(0.3)
−50 0 50 Rank Difference (gene − metabolite)
Node Degree
15
10
5
−log(1) 0
0.00
−log(0.01)
−log10(p)
A
Supplementary Figure 1. Results of integrative analysis carried out using gene-expression and metabolomics data. A) Heatmap overview of matched prostate cancer derived gene expression and metabolomic data (Benign=16, PCa=12). B) Top pathways independently enriched using gene expression and metabolomic data with associated gene (blue)/metabolite (red) ranks. C) Chart representing the concordance between gene-expression and metabolomics data. X axis represents the pathway rank difference derived from gene and metabolite data. Y axis represent common pathways independently enriched using gene and metabolite data. D) Graphical representation of overall enrichment of 5 pathways (refer to main text). The length of each arrow correlates with overall enrichment p value. Y axis represents overall density of interaction across biochemical network in KEGG. X axis depicts the total number of interactions for 5 enriched pathways.