I have recently tried to implement the Samon-Tximport-DESeq2 pipeline with my latest RNA-Seq dataset however I have a problem with some of the downstream analysis and potential compatibility with other programs. I have found that the dataset has quite large batch effects and I am hoping to regress these out prior to downstream analysis (mainly WGCNA). My general workflow at present has been to use tximport to get gene-level count estimates and then to run the standard DESeq2 pipeline from there.
I was then planning to normalize these counts (vst) and run a simple regression on the transformed object to remove the effects of batch. The residuals I would then use for WGCNA. My concern however is that it is mentioned throughout the documentation that one should not normally use these transformed objects for any purpose involving DE. I was hoping to get some advice on whether this would be appropriate and if not, what other methods may be more suitable. I have a general population cohort and I am looking at more covariates of interest than disease status (age, gender, family history etc etc).