A system for fast, accurate, and flexible whole genome bisulfite sequencing (WGBS) data analysis of two-condition comparisons. Principal Component BiSulfite, 'PCBS', assigns methylated loci eigenvector values from the treatment-delineating principal component in lieu of running millions of pairwise statistical tests, which dramatically increases analysis flexibility and reduces computational requirements. Methods: < https://katlande.github.io/PCBS/articles/Differential_Methylation.html>.