I am using edgeR for DEG analysis. I am trying different methods for normalization: "RLE", "TMM", "upperquartile". The three methods give me similar results, but these results do not make any sense for the type of comparisons that I am making. I mean that genes that have to be down-regulated are up-regulated.
When I used the method "none", I obtain the opposite results and these make a lot of sense. When the normalization method "none" is chosen, it means that the normalization is performed on total counts?
Does anyone still do normalization on total counts with edgeR? I read that this type of normalization is not reccomended, but still in my case it looked the most appropriate.