Figure 1.

Normal and NTDs human fetal brain metabolome

(A) PLS-DA to distinguish the global metabolic differences between groups and identify the differential metabolites between NTDs and Con group (n = 30).

(B) Heatmap of all differential 111 metabolites between the NTDs and Con fetal brain tissue (n = 30, all p < 0.05, the p values are described in Table S1).

(C) PCA analysis was performed to visually explore the similarity and variations between NTDs subgroups samples’metabolic composition. The percentages in parentheses refer to the proportions of variation explained by each ordination axis. N = 8 in Anencephaly subgroup. N = 17 in Spina Bifida subgroup. N = 5 in Anencephaly and Spina Bifida subgroup. (D, left) Brain folate concentration was related to brain metabolites by Mantel tests. Edge width corresponds to the Mantel’s P statistic, and edge color red/blue connections indicate a positive/negative correlation. Top10 metabolites that strongly correlate with brain folate concentrations are shown. Pairwise comparisons of these brain metabolites are shown, with a color gradient denoting Spearman’s correlation coefficients. (D, right) Bubble plots of metabolite abundance in each NTDs subgroup,∗<0.05,∗∗<0.01 “Spina Bifida” compared to “Anencephaly and Spina Bifida” subgroup; #<0.05, ##<0.01 “Anencephaly”compared to “Anencephaly and Spina Bifida” subgroup, the p values are described in Table S2.

(E) Diagnostic outcomes are shown via receiver operating characteristic (ROC) curves for brain folate concentration among 60 subjects.

(F) Functional pathways significantly regulated by brain metabolite of NTDs and controls (all p value < 0.05, the p values are described in Table S3).