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Table 1 Biochemical pathways with metabolites changed by antipurinergic therapy in the Fragile X mouse model

From: Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model

No. Pathway name Measured metabolites in the pathway (N) Expected pathway proportion (P = N/673) Expected hits in sample of 58 (P * 58) Observed hits in the top 58 metabolites Fold enrichment (Obs/Exp) Impact (Sum VIP score) Fraction of impact (VIP) explained (% of 136.0) Suramin treatment effect (KO-Sur/KO-Sal)
1 Purine metabolism 41 0.061 3.54 5 1.41 27.2 20.0% 4/5 Decreased
2 Fatty acid oxidation and synthesis 39 0.057 3.37 9 2.67 16.8 12.4% 9/9 Decreased
3 Eicosanoid and resolvin metabolism 36 0.053 3.11 6 1.93 14.7 10.8% 4/6 Increased
4 Ganglioside metabolism 12 0.018 1.04 6 5.79 13.4 9.8% 6/6 Increased
5 Phospholipid metabolism 115 0.18 9.93 6 0.60 11.5 8.5% 6/6 Increased
6 Sphingolipid metabolism 72 0.105 6.21 5 0.80 11.1 8.2% 3/5 Decreased
7 Microbiome metabolism 33 0.047 2.85 3 1.05 6.7 4.9% 2/3 Decreased
8 SAM, SAH, methionine, cysteine, glutathione metabolism 22 0.032 1.90 3 1.58 6.7 4.9% 3/3 Increased
9 Vitamin B3 (Niacin, NAD+) metabolism 8 0.012 0.69 2 2.90 5.2 3.8% 1/2 Increased
10 Glycolysis and gluconeogenesis 18 0.026 1.55 2 1.29 4.2 3.1% 2/2 Decreased
11 Cholesterol, cortisol, non-gonadal steroid metabolism 29 0.042 2.50 2 0.80 3.2 2.4% 2/2 Increased
12 Nitric oxide, superoxide, peroxide metabolism 6 0.009 0.52 1 1.93 2.1 1.5% Increased
13 Cardiolipin metabolism 12 0.018 1.04 1 0.97 2.0 1.4% Decreased
14 Bile salt metabolism 8 0.012 0.69 1 1.45 1.8 1.3% Increased
15 Branch chain amino acid metabolism 13 0.019 1.12 1 0.89 1.7 1.2% Increased
16 Isoleucine, valine, threonine, or methionine metabolism 4 0.006 0.35 1 2.90 1.7 1.2% Increased
17 Pyrimidine metabolism 31 0.051 2.68 1 0.37 1.6 1.1% Decreased
18 Krebs cycle 17 0.025 1.47 1 0.68 1.6 1.1% Increased
19 Vitamin B6 (pyridoxine) metabolism 5 0.007 0.43 1 2.32 1.5 1.1% Increased
20 Pentose phosphate, gluconate metabolism 11 0.016 0.95 1 1.05 1.5 1.1% Increased
  20 of 60 pathways dysregulated 532 (0.79 x 673) 79% (532/673) 46 (0.79 x 58) 58   136.0 100% 33/58 Increased
  1. Pathways were ranked by their impact measured by summed VIP (ΣVIP; variable importance in projection) scores. A total of 58 metabolites were found to discriminate suramin-treated and saline-treated Fragile X knockout groups by multivariate partial least squares discriminant analysis (PLSDA). Significant metabolites had VIP scores of ≥1.5. Twenty (33%) of the 60 pathways interrogated had at least one metabolite with VIP scores ≥1.5. The total impact of these 58 metabolites corresponded to a summed VIP score of 136. The fractional impact of each pathway is quantified as the percent of the summed VIP score and displayed in the final column on the right in the table. Antipurinergic therapy with suramin not only corrected purine metabolism, but also produced changes in 19 other pathways associated with multi-system improvements in ASD-like symptoms.