What are the limitations of whole genome bisulfite sequencing (WGBS)?

WGBS is expensive compared to targeted methods due to the extensive sequencing coverage required for comprehensive genome-wide analysis. It also requires high amounts of input DNA and requires a high number of reads to get the right sequencing depth. The analysis of WGBS data requires significant computational resources, particularly for alignment. Another con is that because of the excessive PCR cycles and the use of a DNA polymerase insensitive to uracil, it can lead to an overrepresentation of methylated DNA sequences in the data.