Batch correction without biological covariates

Question

[as823jk]

In general, is it ever acceptable to use Combat-seq (or any other batch correction method) without providing any biological covariates?

Combat-seq will run fine if you don't provide any biological covariates, but wouldn't this prevent the model from being able to distinguish between biological variation and batch variation?

Answer 1

[swbarnes2]

Well, hopefully your batch variation has nothing to do with your biological variation.

If they overlap, like all your controls are one batch, and all your treateds are a second batch, there is no way to batch correct that.