Epic Methylation analysis on Glycogen Storage Disorder type 1a and Healthy Controls fibroblasts

An analysis of differences in the genomic methylation pattern between GSD1a and HC samples using the Illumina EPIC V2 array as shown in the Disease-associated programming of cell memory in glycogen storage disorder type 1a manuscript. To assess the global differences between samples from the two groups, we used the full dataset of processed probes and initially performed a regression analysis with the aim to assess the in-group variability for each of HC and GSD1a groups tested. Results from this analysis showed lower variability in the GSD1a group which implies that GSD1a fibroblasts present a methylation phenotype that is consistent between group samples as compared to the HC samples. These differences were also observed by an unsupervised clustering analysis that we performed based on K-means searching for two clusters between our 8 tested samples and by PCA. Differential methylation analysis comparing GSD1a to HC cells was performed. Thousands of significantly different probe signals between the groups were found. Differential methylation region analysis which is based on methylated probes distribution located at similar regions in the genome, obtained many differentially methylated regions (DMR) between the groups. GSEA comparing GSD1a cells to HC cells using the methylation dataset and the GO database revealed significantly enriched pathways related to lysosomal and metabolic pathways. In addition, pathways related to epigenetic modifications are also differentially enriched between GSD1a and HC cells. An integratino of this experiment with ATAC-seq and RNA-seq data is shown in the manuscript.