Exploring metabolic pathway disruption in the subchronic phencyclidine model of schizophrenia with the Generalized Singular Value Decomposition

Table 4 Hypergeometric probability of KEGG defined metabolic pathways in the top cluster in Figure 11

KEGG Path-way Identity	KEGG Pathway	Number of metabolites in cluster(A)	Total number of pathway metabolites detected (B)	Hypergeometric Probability (P(X) ≥ k)
ko00190	Oxidative phosphorylation	1	1	0.224
ko00230	Purine metabolism	3	13	0.598
ko00240	Pyrimidine metabolism	2	6	0.406
ko00250	Alanine, Aspartate and Glutamate metabolism	4	7	0.043
ko00260	Glycine, Serine and Threonine metabolism	4	7	0.043
ko00270	Cysteine and Methionine metabolism	3	7	0.186
map00300	Lysine biosynthesis	1	3	0.538
ko00330	Arginine and Proline metabolism	7	10	0.001
ko00340	Histidine metabolism	2	5	0.312
ko00410	beta-Alanine metabolism	2	5	0.312
ko00430	Taurine and Hypotaurine metabolism	1	3	0.538
ko00471	D-glutamine and D-glutamate metabolism	1	1	0.224
ko00480	Glutathione metabolism	1	5	0.728
ko00564	Glycerophospholipid metabolism	1	11	0.949
ko00600	Sphingolipid metabolism	2	3	0.126
ko00640	Propanoate metabolism	1	2	0.400
map00650	Butanoate metabolism	3	4	0.034
ko00680	Methane metabolism	1	1	0.224
ko00760	Nicotinate and Nicotinamide metabolism	3	4	0.034
ko00770	Pantothenate and CoA biosynthesis	2	5	0.312
ko00920	Sulphur metabolism	1	3	0.538
ko04080	Neuroactive ligand-receptor interaction	4	7	0.043

Table 4 shows the hypergeometric probability of at least the observed number of metabolites arising by chance for a given KEGG defined metabolic pathway in the top cluster of Figure 11, identified through the GSVD algorithm as being present in control but not PCP-treated animals. Further computational details are given in the Methods section. The cluster size was 22 metabolites from a total population of 98. There was a significant over representation of metabolites of (i) Alanine, Aspartate and Glutamate metabolism [ko00250], (ii) Arginine and Proline metabolism [ko00330], (iii) Butanoate metabolism [ko00650], (iv) Nicotinate and Nicotinamide metabolism [ko00760], (v) Glycine, Serine and Threonine metabolism and (vi) those metabolites active as neurotransmitter ligands [ko04080] (all highlighted in bold) suggesting that these pathways are disrupted in the PFC of PCP-treated animals.

ISSN: 1752-0509