CellCanon: An Agentic Cellular World Model for Prediction, Explanation, and Observation-Driven

In simulated experimental feedback, Update uses one measured source context per drug to exceed the best fine-tuned baselines in differential-expression AUPRC and Macro-F1 without changing model weights. It comes from a paper posted to arXiv on 5 November 2026. Biological discovery requires using molecular knowledge and new measurements to infer responses beyond the conditions already observed. We introduce CellCanon, the first agentic cellular world model to unify single-cell expression prediction, evidence-grounded explanation, and observation-driven updating. Its predictive core reuses condition-level biological evidence across gene-specific numerical readouts to guide single-cell expression generation. A shared world state links predictions, acquired measurements, and source-linked claims, supporting explanation and revision. On 339 held-out SciPlex3 conditions across three cell lines, CellCanon improves differential-expression AUPRC and Macro-F1 over the best baseline for each metric by 63.3% and 17.3%, respectively, and direction Macro-F1 by 7.2%. Relative to gene-wise reasoning on matched drug-cell cohorts, measured language-model token use falls by 99.77% for Predict and 98.41% for Explain. On the source-grounded benchmark, Explain correctly answers all answerable questions with supporting proofs and identifies all insufficient-evidence cases. Together, these capabilities support a cumulative account of cellular responses, with predictions and biological judgments that can be revised as evidence accumulates.

Why it counts

In simulated experimental feedback, Update uses one measured source context per drug to exceed the best fine-tuned baselines in differential-expression AUPRC and Macro-F1 without changing model weights. On 339 held-out SciPlex3 conditions across three cell lines, CellCanon improves differential-expression AUPRC and Macro-F1 over the best baseline for each metric by 63.3% and 17.3%, respectively, and direction Macro-F1 by 7.2%. We introduce CellCanon, the first agentic cellular world model to unify single-cell expression prediction, evidence-grounded explanation, and observation-driven updating.

Sources

Primary source: primary source

What is not known

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