Got the negative value when used ComBat to Adjust batch effects

Question

[zhao03]

Hi, i used combat to remove the batch bais, however, there are some negative numbers in the result matrix. what is the means of those negative number, can i use this matrix to find the different gene?

i inputted FPKM for running combat.

the command is

combat_edata1 = ComBat(dat=edata, batch=batch, mod=NULL, par.prior=TRUE, prior.plots=FALSE)

thank you

Answer 1

[ATpoint]

This is normal and expected for genes with low counts, you cannot avoid this. combat was developed for arrays, not counts back in the day. Alternatively, use ComBat-Seq from the sva package on the raw counts to remove the batch and then normalized these data. This will preserve the integer-nature of the counts and will not produce negative values.