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. 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. Together, these capabilities support a cumulative account of cellular responses, with predictions and biological judgments that can be revised as evidence accumulates.
Yang Wang, Hongxuan Liu, Xinghui Xu, Arjun Menon, Xiaoran Cai, Yunyu He, Alex Tarvo, Jingzong Zhou 等 43 位作者
Physical intelligence refers to intelligence systems that understand, reason about and act in accordance with the physical world and its underlying laws, dynamics, and constraints. Unlike conventional AI systems, physical intelligence interacts continuously with uncertain physical environments, and its actions produce consequences that are physically irreversible. As existing trustworthy AI frameworks have been developed primarily for digital AI systems, they do not fully capture the distinctive challenges of Physical Intelligence, such as physical safety, cyber-physical security, and physical manufacturing process. To address this gap, our paper develop a foundation for understanding, operationalizing, and governing trustworthy physical intelligence. First, we characterize the fundamental capabilities of physical intelligence. Second, we investigate the role of physical laws and principles in AI and analyze the associated challenges of physical intelligence. Third, we provide a unified structure of the end-to-end physical intelligence life cycle across five core stages and introduce the Trustworthy Physical Intelligence Operationalization (T-PAIO) framework. Fourth, we formulate the Trustworthy Physical Intelligence (T-PAI) Principles as a theoretical framework that synthesizes key trustworthiness dimensions and establishes a conceptual foundation for the governance of physical intelligence systems.
Generating drug-induced transcriptional responses requires a model to account for cellular background together with molecular identity and dose. We present scTREAT, the first diffusion framework to factorize state and drug guidance for single-cell drug-response prediction. A shared latent expression space connects baseline and response, while Guided Decomposable Attention (GD-Attn) injects a baseline representation and a dose-conditioned molecular embedding. Independent channel dropout exposes four conditioning states during training; inference combines three conditional predictions with separately specified state and drug coefficients, and dose modulates drug-guidance strength. On condition-level pseudobulk profiles derived from the Tahoe-100M single-cell atlas, scTREAT achieves the best value on 10 of 12 metrics for unseen cell line-drug combinations (UC) and 11 of 12 for unseen drugs (UD). Ablations examine condition injection, molecular representation, and guidance design. On UD, the relative gains over the second-best model reach 36.11% and 34.21% for DEG logFC-Spearman and logFC-Pearson. These results demonstrate the effectiveness of combining shared latent expression modeling with explicit state and drug conditioning for response prediction.