Genome-wide analysis of differential RNA editing in epilepsy

Figures

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  Figure 1.. (A) Summary of study design for detecting significant differential RNA editing events associated with epilepsy. (B) The figure summarizes the results for the different categories of differential RNA editing analyzed. These categories were generated using two approaches: (1) predicted RNA-editing sites, represented in the outer circle, and (2) predicted and clustered RNA-edited sites, represented in the inner circle and table. The percentages were calculated with respect to unique genes. The outer circle refers to “all” sites, while the inner circle refers to “clustered” sites. A-to-I and C-to-U editing are represented in blue and red, respectively, while all other sites are represented in green. (C) Volcano plot summarizing mean RNA-editing percentages differences in epileptic and control mice and their significance levels. (D) Concordance between RNA-editing events detected using RNA-seq and Sanger sequencing.

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  Figure 2.. (A) Functional annotation of genes harboring differential RNA-edited clustered sites for Gene Ontology (GO) categories phenotype, molecular function, and cellular component. (B) Consequence analysis of the differential RNA-edited clustered sites.

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  Figure 3.. Relationship between RNA editing in the hippocampus and seizure frequency (here, measured as total seizure counts over a standardized period of 14 continuous days of monitoring). (A) Correlation between RNA-editing percentages and total seizure counts in the 100 epileptic mice. (B) Association between RNA-editing fold change and correlation between RNA-editing percentage and total seizures in epileptic mice. C-to-U sites are represented as solid black circles, while A-to-I sites are solid gray circles. All other sites are represented as white circles with a black outline.

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  Figure 4.. (A) For genes impacted by differential RNA editing, enrichment for de novo mutations from patients with epileptic encephalopathy (EE), autism spectrum disorder (ASD), intellectual disability (ID), and schizophrenia (SCZ); enrichment of association to genetic generalized epilepsy (“Epilepsy GWAS”) and enrichment for known epilepsy genes (Epilepsy Genes) (as defined by DisGeNET). (B) Table summarizes the enrichment P-value, odds ratio (OR), and 95th percentile of the confidence interval of the OR and lists the genes contributing to the enrichment of EE de novo mutations (top) and known epilepsy genes (bottom) among genes differentially RNA-edited in epilepsy.