> Two, all the functional annotation is based off transcription profiles. They essentially looked for clusters of genes with correlated expression, and assigned

> Two, all the functional annotation is based off transcription profiles. They essentially looked for clusters of genes with correlated expression, and assigned function based on genes with previous annotations This is an important point, because if you've ever worked with single cell data you'll know that the transcriptional profile is extremely noisy and your transcriptional profile to cell type map has many researcher degrees of freedom. I heard a story about a paper early in the single cell work that started with 53 cell types and after review ended up with 37 cell types. Are those true cell types? Did the experimenters validate that those cell types all performed different functions? Well, of course not. That's way too much work. Then add on technological biases, which make mapping between technologies difficult. I say this because they used a new sequencing technology that appears to have homopolymer bias (https://twitter.com/lpachter/status/1533875723995185153 https://twitter.com/lpachter/status/1533875723995185153), which will bias the gene quantification.