Multi-omic insights into molecular mechanism and therapeutic targets in spinocerebellar ataxia type 7

Recent advances in molecular science have significantly enlightened our mechanistic understanding of spinocerebellar ataxia type 7. To further close remaining gaps, we performed a multi-omics analysis using SCA7(266Q/5Q) mice. Entire brain tissue samples were collected from 12-week-old mice, and RNA sequencing, methylation analysis, and proteomic analysis were performed. Results were integrated to identify genes with identical trends in expression across all three analyses. Data from RNA sequencing and methylation analysis revealed 58 significantly hypomethylated-upregulated genes and 62 hypermethylated-downregulated genes, mostly enriched in GO terms of regulation of axonogenesis, channel activity, and monoamine signaling. In the proteomic analysis, 211 upregulated and 281 downregulated DEPs associated mostly with immune response and cellular mobility were identified. Two genes, Fam107b and Tph2, showed differential expressions in both transcriptomic and proteomic analyses. Findings were validated in RT-qPCR as well as open data source analysis. Our study is the first to perform multi-omics analysis in SCA7 mice and will serve as an important reference for future studies.