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.
Jiayi Luo, Yang Zhang, Liliang Chen, Nan Wang, Chen Gao, Boxiang Qiu, Zhuoxuan Li, Baorui Peng 等 16 位作者
Action-conditioned world models offer a scalable alternative to costly real-world interaction for improving robot policies. However, existing world-model-based methods largely treat world models as forward-only surrogates of the physical environment, leaving untapped a capability no physical environment affords: rewinding to past decision points to explore counterfactual futures. We introduce Rollback, a policy improvement paradigm that turns world models from passive simulators into counterfactual engines: it rolls back to critical decision points, branches into alternative actions, and contrasts their outcomes to attribute success to individual decisions. This concentrates imagination where it matters most and distills counterfactual outcomes into fine-grained, action-level supervision without a separately learned value model. We build a scalable training system that unifies distributed world-model search with asynchronous real-robot execution, forming a self-reinforcing cycle: real-world experience continually sharpens the world model, and a sharper world model in turn drives further policy improvement. We term the world-model side of this cycle test-time physics grounding, a capability that hand-built physics simulators lack: while the world model serves as the training environment, real transitions from the policy it trains correct its dynamics through a lightweight LoRA pipeline. Experiments on three challenging real-world tasks show that Rollback improves success rates over the strongest baseline by an absolute 10.67%, 11.11%, and 11.85% on block extraction, ball tossing, and tabletop curling, respectively, while achieving more stable improvement throughout training. Although initialized from teleoperated demonstrations far below human level, Rollback surpasses the average success rate of human players on both ball tossing and tabletop curling within 8 hours of training.
George Nigmatulin, Valentin Mohl, Sascha Frey, Kang Li, Aramis Marti-Shahandeh, Mihai Cucuringu, Anisoara Calinescu, Jakob Foerster 等 9 位作者
Realistic market impact is essential for generative limit order book (LOB) models to serve as world models for trading agents. If a simulator misprices this mechanism, agents learn policies that are optimal in the simulator but wrong in the real market. Existing metrics assess generated streams purely through distributional comparison with historical data, leaving counterfactual response to an agent's own orders largely unexplored. Here, we show that market impact emerges naturally in neural LOB generators trained solely for next-token prediction. We inject execution-style metaorders into the generated message flow of five autoregressive models across five NASDAQ stocks and measure the response using estimators from the empirical impact literature, validated on baselines whose physics is known in advance. Our benchmark evaluates any message-level generator in three phases: free generation (reading order-flow persistence against price diffusivity); metaorder injection (yielding the impact law's exponent and amplitude); and a post-execution window (measuring relaxation). In addition, comparing each visible injection to a blind, simulator-only control isolates the model's learned response from standard book mechanics. For every model on every stock, we measure how the impact responds as a function of cumulative metaorder participation. Interestingly, we observe emergent impact in generative models of market data, with exponents in the range of 0.63 to 1.21, slightly above the traditional 0.5 of the square-root law of impact. In the family of models tested, we are so far unable to observe impact decay during relaxation. We tentatively attribute this to the still-short context windows of the models. We release the benchmark as open source to validate future generative models for market data.