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Can I use raw read counts from the GTEx data for cross-tissue comparison?

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?

rnaseq gtex statistics normalization

1 answer

This was addressed in a prior thread --> Can I use GTEx RNA-seq gene read data compare the gene expression difference between two tissues?

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