Fig 1.
Identification of DEGs associated with CHD8 deficiency.
(A) Volcano plot of DEGs between wild-type (WT) and CHD8A + /– samples (GSE236993). Red and blue dots represent significantly up- and downregulated genes, respectively; gray indicates non-significant changes. (B) Volcano plot of DEGs between WT and CHD8B + /– samples (GSE236993), as in (A). (C) Venn diagram showing the overlap of DEGs from CHD8A and CHD8B groups with Notch pathway-related genes. A total of 298 genes are primarily linked to Notch signaling. (D) Heatmap depicting expression patterns of the identified DEGs in WT and CHD8-deficient samples. Red represents upregulation, blue represents downregulation.
Fig 2.
GO and KEGG enrichment analyses of shared DEGs.
(A) GO enrichment results showing significant involvement in cell development, nervous system development, neurogenesis, and the Notch signaling pathway. (B) KEGG pathway enrichment highlighting pathways such as PI3K-Akt, TGF-β, and ECM–receptor interaction.
Fig 3.
PPI network and hub gene analysis.
(A) PPI network of identified DEGs, highlighting hub genes such as NOTCH1, FN1, BDNF, and PAX6. (B) Expanded network showing complex interactions among hub genes, indicating a shared regulatory network involved in ASD pathogenesis.
Fig 4.
Validation of hub genes in GSE85417.
(A) Volcano plot of DEGs between wild-type and CHD8-deficient samples from GSE85417. (B) Venn diagram showing seven genes overlapping between GSE236993-derived key genes and GSE85417 DEGs. (C) Heatmap illustrating expression changes of the seven common genes, with LOX, COL11A1, and ITGA6 upregulated, and FBN2 and CXCR4 downregulated in CHD8-deficient samples, supporting their critical roles in ASD pathogenesis.
Fig 5.
Drug–gene interaction network.
Key genes (FN1, COL11A1, CXCR4, IGF2, FBN2) and their potential small-molecule modulators are shown, suggesting possible therapeutic interventions for ASD.
Fig 6.
miRNA–hub gene interaction network.
Identified hub genes (IGF2, COL11A1, CXCR4, ITGA6, LOX, FBN2, FN1) are regulated by multiple miRNAs, suggesting important roles in ASD and potential therapeutic targets.