Fig. 3

Evolution of metabolite intensity differences identified in the prefrontal cortex of ASD individuals. a The relationship among species and individuals plotted as the first two dimensions of the multidimensional scaling (MDS) procedure based on intensities of 1366 metabolites. Circles represent individual samples. Colors represent: ASD individuals (gray), control human individuals (red), chimpanzees (blue), and macaques (green). The size of each circle is proportional to the individual’s age (smaller circles correspond to younger ages). b Metabolite intensity differences between humans and macaques measured using our data (Dataset 1) and a published dataset (Dataset 2)⁴¹. The intensity differences were calculated as log2-transformed differences between the average intensity values within each species. Dots represent individual metabolites detected in both datasets (n = 31). Colors indicate plot quadrants. c Summary of top functional pathways enriched in genes linked to metabolites represented in two categories using KEGG annotation. The categories include: all 202 ASD-related metabolites identified using ANCOVA (ASD-related) and human-specific metabolites (human-specific). The size of each circle is proportional to the number of genes within the pathway linked to metabolites in a given category (smaller circles correspond to a smaller number of genes). The color of each circle indicates BH-corrected enrichment p-values. d The ratio of human-specific and chimpanzee-specific metabolites represented in different categories: all 1366 detected metabolites (Whole Metabolome); all 202 ASD-related metabolites identified using ANCOVA (ANCOVA); and ASD-related metabolites within each module (modules 1–4). Boxes show the first and the third quartiles and the median of the data, the whiskers extend to the minimum and maximum data values located within 1.5 interquartile range from the box. Dashed gray lines indicate the inter-whisker range of the detected metabolites