[timy2shoes]

> this does not sound to me like we know the "function" of these genes, only that they're nessary for each phenotype

But they're not even measuring the phenotype. They're using the transciptional signature as a substitute for phenotype/cell function (i.e. the bag of RNA model). This is a poor substitute if you try to apply this to practical applications such as cell engineering. Let's say I perturb a cell to match it's transcriptional signature to that of a neuron. Does that make it a neuron? Not if it doesn't function like a neuron.

[twic]

I think this is a really important point. With a few exceptions (like the neat implied aneuploidy assay), they haven't measured an outcome or phenotype for the genes. They have measured the impact on transcription (well, mRNA levels, via transcription or some other effect). That is an extremely useful dataset, but it's not enough to say what the phenotypic effect of knocking out any given gene is, much less what the actual mechanistic function of the gene product is.

It's also important to note that there are loads of genes whose effects are not mediated by changes in mRNA levels. If you knock out Arp2, a cell can't move properly, because Arp2 is involved in assembling cytoskeletal structures needed to do that, but you probably won't be able to tell that by looking at the cell's mRNA.