Extended Data Fig. 6: The prefrontal cortex of PD patients does not exhibit differences in the proportion of brain cell types.
From: Epigenomic analysis of Parkinson’s disease neurons identifies Tet2 loss as neuroprotective
Cell-type deconvolution in 24 PD and 12 control prefrontal cortex transcriptomes was performed using 834 cell-type-specific gene signatures63,81. a, Cell-type proportions in the prefrontal cortex of PD patients (orange) and controls (gray). There were no significant differences between PD patients and controls in brain cell types, as determined by a repeated-measures ANOVA and post hoc Tukey HSD test. Boxplot center line is the mean, the bounds of the box are the lower and upper quartiles, and the whiskers extend to minimum and maximum data points within 1.5 times the interquartile range. b, Correlation of neuronal proportions in transcriptomic data with the correction for sources of unknown variation. Statistical analysis of transcriptomic changes in the prefrontal cortex of PD patients was corrected for unknown sources variation, as determined by RUVseq30. P = 10−9 is the significance of Pearson’s correlation by two-tailed t-test, with 95% confidence intervals shown in gray. c, Comparison of statistical models that identifies differentially expressed genes in the PD prefrontal cortex after controlling for unknown sources of variation or neuronal proportion. Differentially expressed genes in the prefrontal cortex of PD patients were identified using a generalized linear model, adjusting for age, sex, RIN, and neuronal proportion or sources of unknown variation (q < 0.05, absolute logFC≥0.5, multiple testing corrected). The outcome of both models is comparable, showing significant overlap of differentially expressed genes in PD (P = 10−228, Fisher’s exact test). d, TET1 and TET3 transcript levels in the prefrontal cortex of PD patients relative to controls. Differentially expressed genes in the prefrontal cortex of PD patients were identified using a generalized linear model, adjusting for age, sex, RIN, and sources of unknown variation. There are no significant changes in TET1 and TET3 transcript levels between PD patients and controls (nominal P = 0.96 and 0.09, respectively). Boxplot center line is the mean, the bounds of the box are the lower and upper quartiles, and the whiskers extend to minimum and maximum data points within 1.5 times the interquartile range. a‒d, n = 12 controls, 24 PD. e, Increased TET2 transcript levels are correlated with reduced TH protein levels in the prefrontal cortex. n = 11 individuals. P = 0.03 is the significance of inverse association between TET2 mRNA and TH protein levels by linear regression. The 95% confidence intervals are shown in gray.
