OnCo
ideasIdea

A virtual cancer cell that predicts what a drug will do before you test it

Train a model on millions of experiments where genes and drugs were altered, so it can predict the effect of a new combination without running the experiment.

Perturbation foundation models trained on Perturb-seq, CRISPR screens and compound-response atlases aim to predict transcriptional and viability responses to unseen perturbations and combinations. The critical missing element is prospective, blinded validation against held-out wet-lab experiments and, eventually, clinical outcomes. Without that, these models risk repeating the overfitting seen in earlier drug-response prediction efforts.

Hypothesis
A perturbation model prospectively predicts the direction and rank order of combination effects in held-out cell contexts substantially better than a strong statistical baseline, and its errors are systematic and characterisable.
Rationale
Combination space is far too large to screen exhaustively, so some form of prediction is unavoidable; the question is whether current models generalise beyond their training distribution, which only blinded prospective tests can answer.
What would test it
A blinded challenge in which teams predict outcomes of 500 unseen perturbation experiments that are then run in a reference laboratory, with results and baselines published in full.
Maturity
speculative
Who has to act
data
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks

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