Published in the RNA Journal in 2020 - this paper argues that if the original RNA amount in the different samples is different, TPM should not be used to find differentially expressed genes.
Seems like a lot of people like to use DESeq/EdgeR, which the paper asserts that fundamentally:
Most genes are not DE.
DE and non-DE genes behave similarly.
Balanced expression changes, that is, the number and magnitude of up- and down-regulated genes are comparable.
When comparing across samples of different RNA amounts, or, worse, across different strains of the same species - is the only way out DESeq/EdgeR? Is DESeq/EdgeR sufficiently robust for a use in such a case?