According to the Chromvar vignette (https://bioconductor.org/packages/release/bioc/vignettes/chromVAR/inst/doc/Introduction.html), "If analyzing single cell data, it can make sense to use peaks derived from bulk ATAC-seq". The wording is confusing. Do they mean use annotation of peaks defined by bulk ATAC-seq as the 'reference' against which to align single cell ATAC-seq reads? Why can't we use a consensus peak set derived from the single cell data instead?
I've read the methods section of the Nature Methods paper (https://www.nature.com/articles/nmeth.4401#Sec3) and I'm still a little unclear on this.
Thanks for your help!
I guess they mean that you should use bulk peaks to create the count matrix that chromVAR analyzes as bulk has higher coverage and therefore creates more reliable peaks.
Thank you! That makes a lot of sense. I'm very new to this (if that wasn't obvious) and I really appreciate your help.
erased and rephrased original q