Fig. 3.

Cross-species functional analysis of ASD-associated circRNA-miRNA-mRNA regulatory axes. a The CircMiMi-identified circRNA-miRNA-mRNA axes that simultaneously comprised DE-circRNAs and DE-miRNAs in ASD. The DE-circRNAs [13] and DE-miRNAs [52] were previously identified using the RNA-seq data from the same postmortem brain samples. b Enrichment analysis of 5 groups of ASD-relevant genes for the target genes of the 1777 axes. ASD-relevant genes included ASD risk genes (i.e., SFARI genes), genes encoding PSD proteins, genes encoding transcripts bound by FMR1 (FMR1 target), ELAVL1 (ELAVL1 target), and RBFOX1 (RBFOX1 target). c Visualization of the 70 circRNA-miRNA-mRNA axes that simultaneously involved DE-circRNAs, DE-miRNAs, and SFARI genes according to the Cytoscape-executable file generated by CircMiMi. The SFARI genes that are also belonged to other groups of ASD-relevant genes are marked in parentheses. d CircMiMi-identified circRNA-miRNA-mRNA axes based on 3 mouse circRNAs that were orthologous to human DE-circRNAs. e Enrichment analysis of SFARI genes (mouse models) for the target genes of the axes illustrated in (d). For (b, e), P values were determined using one-tailed Fisher’s exact test and empirical enrichment analysis, respectively. P values were then FDR adjusted using Benjamini–Hochberg correction. The enrichment odd ratios were shown in parentheses