| Experiment Id | GSE213899 | Name | Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease relevant pathologies |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-07-10 |
| description | There are hundreds of risk genes for autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We used neuron-specific proximity-labeling proteomics (BioID) to identify protein-protein interaction (PPI) networks for 41 ASD-risk genes. Neuron-specific PPI networks included synaptic transmission proteins, which are disrupted by de novo missense variants. The PPI network map revealed convergent pathways including mitochondrial/metabolic processes, Wnt signaling, ion channel activity and MAPK signaling. CRISPR knockout validations revealed an association between mitochondrial activity and ASD-risk genes. The PPI network showed an enrichment of 112 additional ASD-risk genes and differentially expressed genes from post-mortem ASD patients. Clustering of risk genes based on PPI networks identified gene groups corresponding to clinical behavior score severity. Our data reveal that cell type-specific PPI networks can identify previously unknown individual and convergent ASD signaling networks, provide a method to assess patient variants, and reveal biological insight into disease mechanisms and sub-cohorts of ASD. Cortices from Day 21-23 Taok2 WT and KO mice were used for RNA sequencing analysis, with 3 male mice per condition. |
