Epigenetic_variability_chrX

This repository contains the scripts (R Markdown files) that were used for the analyses accompanying the manuscript "The inactive X chromosome accumulates widespread epigenetic variability with age".

In this manuscript, we systematic annotated, interpretated of age-related differences in DNA methylation at the X chromosome at the level of both differences in mean (age-related differentially methylated CpGs, aDMCs) and differences in variability (age-related variably methylated CpGs, aVMCs).

Examples of aDMCs and aVMCs detected in our analysis

The scripts were run in order (from 1 to 10). The purpose of each script is as follows:

• Script 1: Prepare X-chromosome methylation data from BIOS biobank

• Script 2: aDMCs identification by double generalized linear model (DGLM)

• Script 3: aVMCs identification by double generalized linear model (DGLM)

• Script 4: Compare if DGLM results are robust and convincing

• Script 5: aDMCs replication based on two external datasets

• Script 6: aVMCs replication based on two external datasets

• Script 7: Create an annotation file of the Illumina Infinium 450K array with CGI features and XCI status

• Script 8: Fuctional annotatation of XCI related features of aDMCs and aVMCs

• Script 9: Test assocaition between aDMCs/aVMCs methylation and X chromosome gene expression

• Script 10: Identify differentially methylated regions (DMRs) on replicated aDMCs and aVMCs