Table 5.

Integrated pathway analysis combining significant genes and metabolites in clinical nephrosclerosis versus healthy controls

Pathway/metabolism	Enrichment analysis					Topology analysis	Rank
	Total	No. expected	No. found	P	Fold-change
Glycine, serine, threonine	68	11.36	23	0.0004	2.02	3.70	7.50
Phenylalanine, tyrosine, tryptophan	9	1.50	5	0.0089	3.32	2.06	6.85
Methionine and homocystein	63	10.53	19	0.0053	1.80	3.31	5.98
Glycerolipid	72	12.03	20	0.0116	1.66	2.60	4.31
One-carbon pool by folate	28	4.68	10	0.0116	2.14	1.71	3.65
Arginine and proline	102	17.05	30	0.0008	1.76	2.00	3.52
Glycolysis/gluconeogenesis	91	15.21	23	0.0224	1.51	2.27	3.44
N-Glycan biosynthesis	50	8.36	15	0.0134	1.80	1.40	2.51
Phenylalanine	29	4.85	13	0.0003	2.68	0.88	2.35
Butanoate	47	7.85	17	0.0009	2.16	0.88	1.89
Beta-alanine	50	8.36	19	0.0002	2.27	0.76	1.73
Linoleic acid	34	5.68	15	0.0001	2.64	0.57	1.51

Note: Pathways are ranked according to their combined enrichment and topology using multiplication.⁸⁴ The analysis is using hypergeometric test for enrichment and betweenness centrality for topology. Enrichment analysis tests if compounds involved in a particular pathway are represented more often than expected by chance, and data are presented as fold enrichment. Topology analysis takes the pathway structure into consideration when determining which pathways are more likely to be involved in the conditions under study with changes in key positions of a network triggering more severe impact on the pathway than changes on marginal or relatively isolated positions. Analyses were done using MetaboAnalyst 3.0.