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Raw differential gene expression data, data S1, from: Molecular cascades and cell type-specific signatures in ASD revealed by single cell genomics

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DataONE2024-01-16 更新2024-06-08 收录
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Genomic profiling in post-mortem brain from autistic individuals has consistently revealed convergent molecular changes. What drives these changes and how they relate to genetic susceptibility in this complex condition is not understood. We performed deep single nuclear RNA sequencing (snRNAseq) to examine cell composition and transcriptomics, identifying dysregulation of cell type-specific gene regulatory networks (GRNs) in autism, which we corroborated using snATAC-seq and spatial transcriptomics. Transcriptomic changes were primarily cell type-specific, involving multiple cell types, most prominently interhemispheric and callosal-projecting neurons, interneurons within superficial laminae, and distinct glial reactive states involving oligodendrocytes, microglia, and astrocytes. Autism-associated GRN drivers and their targets were enriched in rare and common genetic risk variants, connecting autism genetic susceptibility and cellular and circuit alterations in the human brain. This da..., Please see Manuscript for detailed information. In Brief: we generated Pseudobulk expression ASD vs CTL analysis by cell type. We generated pseudobulk counts for each sample by adding counts from the same cell type. Then pseudobulk counts are normalized by variance stabilizing transformation method. To identify genes differentially expressed in ASD compared to control in each cell type, we examined covariates with top 5 PCs from normalized pseudo-bulk expression matrix. We identified the following covariates consistently correlated with top 5PCs for each cell type: age, PMI, BrainRegion, SeqBatch, Mito_perc, and ngenes. We then randomly selected subjects 500 times and calculated average beta to regress out effects of these covariates. Then we used limma-voom to identify differentially expressed genes for each cluster., , # Raw differential gene expression data, data S1, from: Molecular cascades and cell type-specific signatures in ASD revealed by single cell genomics Raw Differential Gene Expression data, Data S1, from \"Molecular cascades and cell type-specific signatures in ASD revealed by single cell genomics\" ## Description of the data and file structure Excell document with raw differential gene expression ASD vs. CTL per cell-type cluster. The first column is a drop-down selection to select which cell-type to view the differential gene expression results. The second (ASDvCTL) and third (CTLvASD) columns are the LOGFC value for each differential gene for a given cell type, the fourth (ASDvCTL) and fifth (CTLvASD) column are the p-values for each gene for a given cell type, the sixth (ASDvCTL) and seventh (CTLvASD) columns are the FDR-values for each gene for a given cell type, and the last column is the gene name. ## Sharing/Access information Links to other publicly accessible locations of t...
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2025-07-26
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