RRB sequencing
REGRESSION
RRBS raw reads were trimmed for adaptor sequences using trim galore (v. 0.6.5) (The methylation of the considered genomic feature was computed by first overlapping the CpG positions with GRCh38 genomic feature localizations using GenomicRanges R package (v. 1.48.0)Repetitive DNA feature localizations (Long interspersed nuclear elements, LINE; Short interspersed nuclear elements, SINE; and Long terminal repeat elements, LTR) were retrieved from UCSC RepeatMasker annotation (genome assembly GRCh38/hg38) using AnnotationHub R package.To investigate associations between CpG site-specific DNA methylation of genomic features and clinical response, robust linear regression models were fitted at each treatment time point for considered patients’ groups using the MASS R package (v. 7.3–58.3).Human GRCh38 annotated genes and promoters exhibiting differential DNA methylation between predefined groups of patient samples were identified using R package limma (v. 3.44.3)