Does bisulfite sequencing need higher sequencing depth than regular genomic sequencing?

Question

[Qingyang Xiao]

Hello! What's the biggest differences between bisulfite sequencing and regular genomic sequencing?

Is it higher depth for BS-sequencing is nessary to identify methylation signature than other kinds of genotyping?

For the bisulfite treatment, I it will reduce the DNA sequence complexity. Apart from this, are there some other trick points in this library preparation(steps/techniques) than other regular genomic libraries?

Personally, short clear answers in one or two sentences are preferred. And bomb me with the links. Wish you all guys have a nice weekend.

Answer 1

[Chris Miller]

It depends on your experimental design and what information you hope to retrieve.

That said, if anything, lower coverage is needed. 2-3x gives reasonable results when you leverage the fact that the methylation of nearby CpGs are heavily correlated. 10x gives really nice CpG-level resolution across the genome.

Choose your bisulfite read aligner carefully - some are much better than others.