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).