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Fig. 4 Integrated omics identify SCGN as a key regulator of immune response and oxytocin signaling pathways. a Multi-omics profiling of zebrafish and mice samples. Zebrafish whole brain and Mice hypothalamus were extracted for transcriptome analysis. Mice serum was collected for metabolome analysis. Transcriptome and metabolome from mice were further integrated for association analysis. b Volcano plots of GSEA results based on differentially expressed genes in the hypothalamus of scgn+/+ and scgn−/− mice. The dot color indicated the −log10 p-value in each pathway, while the dot size represented the gene number of each pathway. NES Normalized Enrichment Score. Volcano plots shows inflammatory and immune response pathways were signatures based on mice transcriptome analysis. c GSEA plot shows the signatures of the immune response in hypothalamu transcriptomes by scgn−/− mice compared to scgn+/+ mice. NES Normalized Enrichment Score. P, p-value. FDR False Discovery Rate. d, e Relative mRNA expression of immune and inflammation related genes upon brain tissue in scgn+/+ and scgn−/− mice after exposure to Bleed challenges (n = 3). d IL-6; e TNF. N = 3 for each group. Data were presented as mean ± SD, P-values were calculated using one-way ANOVA, Tukey’s multiple comparisons test. ***p < 0.001, **p < 0.01, *p < 0.05, ns not significant. f Plasma IL-6 protein level is increased in scgn−/− mice relative to control. **p < 0.01. Differences among groups by unpaired Student t-test. Experiments above were repeated three times. g Plasma IL-1β protein level is increased in scgn−/−mice. ***p < 0.001. P-values were calculated using unpaired Student t-test. Experiments above were repeated three times. h Mice transcriptome& metabolome association analysis reveals difference of oxytocin signaling pathways and neuroactive ligand-receptor interaction. i Plasma oxytocin concentrations of scgn−/− mice is decreased. N = 8 for each group. Data were presented as mean ± SD, P-values were calculated using one-way ANOVA, Tukey’s multiple comparisons test. **p < 0.01. j Plasma concentrations of oxytocin in 3 control individuals, 2 ASD children without scgn mutation, ASD0010 and ASD0014 proband. ASD0010 and ASD0014 showed a lower plasma oxytocin levels than control and ASD1, ASD2. Ctl: control, healthy children; ASD1 and ASD2: ASD probands who do not carry scgn mutations; ASD0010: ASD individual carries mutation SCGN p.R79W; ASD0014: ASD individual with mutation scgn c.702 + 2 T > G. All individual in this test ages are around 3 years old. Experiments above were repeated three times