Pathway topology analysis in the discovery set
To analyze the most relevant pathways after identifying differential
metabolites, the metabolic pathway topology enrichment analysis was
applied with the impact value to evaluate the importance of the pathways
underlying the pathophysiology mechanism in different asthma phenotypes
and healthy subjects (Figure 3). As a result, histidine metabolism
(P = 0.019; impact value = 0.189) was identified between asthma
patients and healthy subjects. Differential metabolites between EA and
NA were involved in glycerophospholipid metabolism (P = 0.015;
impact value = 0.121), nicotinate and nicotinamide metabolism (P= 0.020; impact value = 0.332) and histidine metabolism (P =
0.022; impact value = 0.189). Differential metabolites between EA and
PGA were involved in glycerophospholipid metabolism (P = 0.001;
impact value = 0.186), linoleic acid metabolism (P = 0.001;
impact value = 1.000), histidine metabolism (P = 0.014; impact
value = 0.189) and phenylalanine, tyrosine and tryptophan biosynthesis
(P = 0.046; impact value = 0.500). Differential metabolites
between NA and PGA were involved in linoleic acid metabolism (P =
0.002; impact value = 1.000), glycerophospholipid metabolism (P =
0.010; impact value = 0.160) and nicotinate and nicotinamide metabolism
(P = 0.015; impact value = 0.332).