Increased A-to-I RNA editing in atherosclerosis and cardiomyopathies

Figures

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  Fig 1. RNA editing in coding sequences is exceptionally high in arteries. (a) Coding Editing Index of all GTEx samples, presenting the editing level per donor as a weighted average over 314 coding editing sites. (b) Clustering tissues by the profile of editing levels for the 314 sites (calculated for pooled GTEx data). Columns correspond to editing sites meeting cutoff values of ≥ 5% editing and expression in at least five tissues. Colors represent the editing percent at each site. The values correspond to the pulled average per site for all samples meeting the specified cutoffs for each site. Arrows indicate the positions of IGFBP7, FLNA, NEIL1, CCN1 and SRP9, the sites where most cardiovascular editing takes place. (c) The relative contribution of specific coding sites to the overall recoding activity. Notably, all highly edited sites are recoded (editing causes an amino-acid change) and evolutionarily conserved across mammals—samples from left ventricles of unselected GTEx donors.

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  Fig 2. RNA-editing in Alu sequences in atherosclerosis and cardiomyopathies. AEI demonstrates consistently increased editing levels of all Alu sequences in (a) atherosclerosis (ASCVD: red; controls: White; Cerebrovascular: yellow) and (b) CMPs (Patients: red; Controls: white) patients, and hypo-editing in cerebrovascular patients. The DCM and ICM groups are compared to the same control group. Note that due to differences in read length, the nominal index values cannot be compared across the two panels. The exact p-values are detailed in Tables 1 and 2.

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  Fig 3. Interferon stimulated genes and ADAR1 expression in CMPs. Interferon Signature (ISG) Score in (a) CMPs and (b) ICM patients. ADAR1 expression levels in transcript per million units in patients with (c) CMPs and (d) ICM. The exact p-values are detailed in Tables 1 and 2.

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  Fig 4. The landscape of coding editing in cardiovascular patients. Coding Editing Index distribution in (a) Aortae of cerebrovascular and (b) ASCVD patients. (c) Heatmap summarizing all significant (FDR cutoff of ≤ 0.05) and meaningful (editing index difference ≥ 5%) coding editing sites in cardiovascular tissues from GTEx data. Columns are editing sites. Rows represent individual samples of cardiovascular tissue taken from donors with either cardiac or cerebral disease. The heatmap presents 139 patients who have information for at least 70 editing sites. We calculated the change in editing levels for each patient in each site by subtracting the control group average at that site. The color represents the direction of change (blue, elevated editing levels; red, reduced editing levels). (d) Summary of the significant changes in editing in the cardiomyopathies cohorts. Columns are editing sites that differentiate patients from controls in at least one disease type. Colors represent the mean difference in editing levels compared to controls. Gray cells represent missing data or differences not meeting the significance cutoff. Significance is defined by the Wilcoxon rank-sum test p-values…