Fig. 4: Phenotype-specific transcriptomic alterations.

A Circular heatmap of the distribution of the eight neurological phenotypes across the 151 NDD datasets. B The signed -log₁₀ P value of the Cerebellar Purkinje cell layer formation GO-BP term across the different datasets. A negative and positive signed -log₁₀ P value were calculated through Gene Set Enrichment Analysis (GSEA) and indicates down- and upregulated expression, respectively. C log₂ odds ratio (OR) of differential expression in seizure- versus non-seizure-associated neurodevelopmental disorders for all genes associated with cerebellar Purkinje cell layer formation. LHX1 has the highest OR. The lines indicate different types of protein-protein and gene-gene relationships from GeneMANIA (version 3.5.3). D log₂FC profile and their 95% confidence interval of the LHX1 gene in seizure- and non-seizure-associated neurodevelopmental disorders. E LHX1 expression levels across different brain regions in six different datasets available from the Human Protein Atlas: HPA (Human), FANTOM, GTEx, HPA (Pig), HPA (Mouse), and Allen Mouse Brain Atlas. The Z-score was calculated for each dataset separately. F UMAP plot of the cerebellar vermis scRNA-seq data from the Human Brain Atlas v1.0. The LHX1 expression in the different superclusters is shown. Specifically, 51 and 28% of the cerebellar inhibitory and upper rhombic lip cells, respectively, express LHX1.