The DESeq2 vst rlog size factors computations account for differences in library composition amongst other things. Library composition differences between sample groups are one of the reasons for not using TPMs. However, we are often presented only with TPM values. I wondered if there are existing methods for quantifying a library composition problem from a set of TPM values and if not what might be a good way to quantify the risk of using the TPMs (for visualisation or other purposes). For example, would starting off by computing a matrix of pairwise Kolmogorov-Smirnov tests for sample count distributions and find significant differences do the trick?