I am using DESeq2 in my RNA-Seq analysis, and I am wondering whether it is possible to use the median of ratio normalization for calculation of a signature score (an average across the genes in a signature)?
This post (https://hbctraining.github.io/Training-modules/planning_successful_rnaseq/lessons/sample_level_QC.html) claims that the median of ratios normalization is not suitable for within sample comparisons. I struggle to understand why this is the case, since a sum of negative binomial distributions is a negative binomial distribution. Or is MRN not suitable for within sample comparisons but suitable for a signature score calculation?
Thank you so much!