Fig. 3: Identification of epilepsy-associated pathways and transcriptomic shifts across neuronal subtypes. | Nature Communications

Fig. 3: Identification of epilepsy-associated pathways and transcriptomic shifts across neuronal subtypes.

From: Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis

Fig. 3: Identification of epilepsy-associated pathways and transcriptomic shifts across neuronal subtypes.The alternative text for this image may have been generated using AI.

a GO-term enrichment analysis ordered by neuronal subtype reveals both subtypes with large transcriptomic changes (>100 GO terms) and subtypes with only few or no enriched GO terms in the epileptic dataset. The total number of GO terms that passed the 0.05 threshold for the adjusted P value of the overrepresentation test is shown on the y axis. Colors of the stacked barplot represent the top-level GO term: biological process (BP), cellular component (CC), or molecular function (MF). b The major groups of GO terms clustered by their level of enrichment per subtype reveal common transcriptomic shifts across neuronal subtypes in the epileptic brain. Rows correspond to GO terms, ordered according to hierarchical clustering. Columns correspond to cell types. Colors represent –log10 of adjusted P values of the overrepresentation test, trimmed with the upper boundary of 10. c For the blue cluster in (b), the plot shows a UMAP embedding of the GO terms per each subtype. Each point corresponds to a single square on the heatmap in (b). The distances between points are proportional to the Jaccard distance of the enriched genes between two given GO terms in certain subtypes. Thus, points, which are close to each other on the plot, are represented by similar sets of the enriched genes. Left—colored by subtype, right—colored by GO term. The numbers on the right panel indicate GO terms in a subcluster outlined by the dashed line. d Heatmap showing neuronal subtypes grouped based on Jaccard similarity of the enriched “Biological Pathway” GO terms. Rows and columns correspond to cell types, and the intersection represents the weighted Jaccard similarity between the two subtypes. Bold lines separate high-order clusters; neuronal subtypes labeled by the orange and green colors correspond to GABAergic interneurons and principal neurons, respectively. Such a clustering allows to identify groups of subtypes, where each group might correspond to a local circuit/network.

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