Fig. 5: Integrative analysis of Acetylome and RNA-seq highlights histone marks and genes specifically involved in the crucial step of neuronal differentiation in RTS.

a Individual plot of multifactorial analysis (MFA) integrating the two data types: Gr1 (Acetylome) data corresponds to the logFC for acetylation of 25 histones marks provided by the acetylation analysis. For data of Gr2, the logFC of the top DEG genes is provided by the DESeq2 DEG analysis. At each time points, all controls samples are pooled to serve as baseline for individual acetylation or DEG analysis of RTS samples. As in Fig. 3a, the strongest signal (component 1) separates D20 samples from D10 and D60. b Individual plots of MFA analysis focused on neurone development. The analysis integrates two groups data types. Gr1 are similar to in (a). For Gr2, the analysis is restricted to the logFC of the seven selected genes related to neurone development. As in panel (a), the strongest signal (component 1) for RTS samples vs controls separates D20 samples from D10 and D60. c The barplot shows the Confidence Intervals for variable weights driving Component 1 of MFA analysis in (a). Only variables with robust contribution to component 1 are shown: CI do not overlap with 0 on 2000 fold Bootstrap. Except for H2BK23, all histone marks show stronger hypoacetlylation for RTS samples vs controls at D20 (vs. D10 and D60). Correspondingly, positive weights shows DEGs for RTS samples vs. controls that are more strongly downregulated at D20 (vs. D10 and D60) and negative weights corresponds to DEGs for RTS vs controls that are less downregulated at D20 (vs. D10 and D60). d The barplot shows the Confidence Intervals for variable weights in Component 1 for the MFA in (b). Only variables with robust contribution to component 1 are shown: CI do not overlap with 0 on 500-fold Bootstrap. All variable weights are positive: for RTS samples vs. controls. SOX3 gene shows a stronger downregulation at D20 (vs. D10 and D60), as well as stronger hypoacetylation of 11 histone marks at D20 (vs. D10 and D60).