But what I’ll say is, ideally they would demonstrate whether this model can perform any better than simple linear models for predicting gene expression interactions.
We’ve seen that some of the single cell “foundation” models aren’t actually the best at in silico perturbation modeling. Simple linear models can outperform them.
So this article makes me wonder: if we take this dataset they’ve acquired, and run very standard single cell RNA seq analyses (including pathway analyses), would this published association pop out?
My guess is that yes… it would. You’d just need the right scientist, right computational biologist, and right question.
However, I don’t say this to discredit the work in TFA. We are still in the early days of scSeq foundation models, and I am excited about their potential.
Cellular level computational simulation existed a very long time and it's more impressive by the day because of large collections of experimental datasets available.
However to infer or predict celular acitivities you need a ton of domain knowledge and experties about particular cell types, biological processes and specific environments. Typically the successful ones are human curated and validated (e.g large interaction networks based on literature).
In cancer it's even more unpredictable because of the lack of good (experimental) models, in-vivo or in-vitro, representing what actually happens the clinically and biologically underneath. Given the single cell resolution, its uncertainty will also amplify because of how heterogeneous inter- and intra- tumours are.
Having said that, a foundation model is definitely the future for futher development. But with all of these things, the bigger the model, the harder the validation process.
j_bum|4 months ago
But what I’ll say is, ideally they would demonstrate whether this model can perform any better than simple linear models for predicting gene expression interactions.
We’ve seen that some of the single cell “foundation” models aren’t actually the best at in silico perturbation modeling. Simple linear models can outperform them.
So this article makes me wonder: if we take this dataset they’ve acquired, and run very standard single cell RNA seq analyses (including pathway analyses), would this published association pop out?
My guess is that yes… it would. You’d just need the right scientist, right computational biologist, and right question.
However, I don’t say this to discredit the work in TFA. We are still in the early days of scSeq foundation models, and I am excited about their potential.
dumb1224|4 months ago
However to infer or predict celular acitivities you need a ton of domain knowledge and experties about particular cell types, biological processes and specific environments. Typically the successful ones are human curated and validated (e.g large interaction networks based on literature).
In cancer it's even more unpredictable because of the lack of good (experimental) models, in-vivo or in-vitro, representing what actually happens the clinically and biologically underneath. Given the single cell resolution, its uncertainty will also amplify because of how heterogeneous inter- and intra- tumours are.
Having said that, a foundation model is definitely the future for futher development. But with all of these things, the bigger the model, the harder the validation process.