I am doing a project in which I am using data generated from GTEx v10. I am trying to compare how the same gene differs quantitatively, for example: in liver vs blood (provided they are expressed in both), and perform downstream statistical analyses. However, the GTEx portal states the following, in regards to TPM:
It is not possible to directly compare these values across tissues. Unfortunately, no computational method can be applied for proper between-sample normalization across the diverse set of tissues represented in GTEx. For further details, please see this paper: https://doi.org/10.1016/j.cell.2012.10.012. The gene expression visualizations therefore provide a qualitative measure of relative expression.
For cross-tissue comparison, what is the best approach? I have thought about using Combat, but I don't have batch information. Also, does DESeq2 driven normalization work in this case?