Metabolomic changes during cellular transformation monitored by metabolite-metabolite correlation analysis and correlated with gene expression.
To investigate metabolic changes during cellular transformation, we used a1H NMR based metabolite-metabolite correlation analysis (MMCA) method, which permits analysis of homeostatic mechanisms in cells at the steady state, in an inducible cell transformation model. Transcriptomic data were used to further explain the results. Transformed cells showed many more metabolite-metabolite correlations than control cells. Some had intuitively plausible explanations: a shift from glycolysis to amino acid oxidation after transformation was accompanied by a strongly positive correlation between glucose and glutamine and a strongly negative one between lactate and glutamate; there were also many correlations between the branched chain amino acids and the aromatic amino acids. Others remain puzzling: after transformation strong positive correlations developed between choline and a group of five amino acids, whereas the same amino acids showednegativecorrelations with phosphocholine, a membrane phospholipid precursor. MMCA in conjunction with transcriptome analysis has opened a new window into the metabolome.
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
Basetti
B
Madhu
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
Masako
M
Narita
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Early Clinical Biometrics, AstraZeneca AB R&D, Mölndal, Sweden.
Alexandra
A
Jauhiainen
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
Suraj
S
Menon
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
Marion
M
Stubbs
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
Simon
S
Tavaré
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
Masashi
M
Narita
Li Ka Shing Centre, Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE UK.
John R
JR
Griffiths
Cellular transformation; Metabolite correlations; Metabolomics; NMR