Genome-wide DNA Methylation Profiling

Genomic DNA underwent bisulfite conversion using the EZ DNA Methylation kit (D5004, Zymo Research), followed by amplification, fragmentation, and hybridization to Infinium EPIC 850k Human DNA Methylation BeadChips (20020530, Illumina) according to manufacturer’s instructions at the University of Southern California Molecular Genomics Core. Bioinformatic analysis was performed in R (v4.2.1). SFT or meningioma DNA methylation data were preprocessed using the minifi pipeline^{30 (link)}. In brief, probes were filtered and analyzed using normal-exponential out-of-band background correction, nonlinear dye bias correction, p-value with out-of-band array hybridization masking, and β value calculation (β=methylated/[methylated+unmethylated]). Principal component analysis was performed on the β methylation values from minfi pre-processing pipeline in R. Variable probes were identified from the first three principal components (PCs). PCs greater than 4 contributed to less than 5% of β value variance. The top 2000 probes were selected for analysis by ranking the absolute gene loading score values within PCs and the tumors were projected along the first two PCs.