Yuwei Miao, Jingquan Yan, Hehuan Ma, Thao M. Dang, Lin Xu, Siyuan Zhang, Junzhou Huang
Predicting gene expression under perturbations from single-cell data is a fundamental task for modeling cellular responses, with applications in discovering gene function and designing therapeutics. However, existing methods often struggle to generalize across datasets due to differences in experimental protocols, biological contexts, and species. We present \textbf{CytoWave}, a perturbation-centric pretraining framework for single-cell genetic perturbation response prediction. We leverage large-scale cross-species perturbation datasets unified via orthology and train CytoWave in a two-stage manner. In the first stage, we learn reference control cell states via masked gene expression recovery on unperturbed cells. In the second stage, we pretrain the model to predict perturbed gene expression given control states and perturbation signals, together with a contrastive objective that aligns latent representations of perturbation responses with perturbation signals. We perform strict dataset-held-out evaluation across multiple condition combinations and case studies of pathway activity changes, demonstrating consistent and effective performance of CytoWave in predicting single-cell genetic perturbation responses.
Boyuan Zhang, Yingjun Du, Xiantong Zhen, Ling Shao
Joint-embedding world models enable visual planning by learning action-conditioned dynamics in latent space. Yet they are commonly trained for one-step prediction on encoded states, while planning recursively applies the learned transition to its own predictions. One-step accuracy therefore does not capture how prediction errors propagate under recursive rollout. We decompose multi-step rollout error into the errors introduced at individual steps and their propagation through subsequent transitions. We show that state-affine dynamics are precisely the differentiable transitions with state-independent Jacobians, eliminating the nonlinear propagation residual and making the error propagation operators depend only on the action sequence. Guided by this result, we introduce SALT (State-Affine Latent Transition), an action-conditioned state-affine dynamics model in which the action modulates both the state transformation and the additive update. We train SALT through recursive multi-step rollout supervision, feeding each predicted latent state back into the transition so that training matches how the model is used during planning. Across four visual planning environments, SALT exhibits $1.48$--$2.19\times$ higher one-step prediction error than the matched LeWM baseline, yet improves closed-loop success in every environment by $10.0$ percentage points on average. On OGBench-Cube, the fraction of episodes that fail with a sharp rise in model-predicted cost after execution decreases from $23.3%$ to $2.0%$.
Underdamped Langevin dynamics (ULD) is a widely-used sampler for Gibbs distributions $π\propto e^{-V}$, and is often empirically effective in high dimensions. However, existing non-asymptotic convergence guarantees for discretized ULD typically scale polynomially with the ambient dimension $d$, leading to vacuous bounds when $d$ is large. The main known dimension-free result concerns the randomized midpoint discretization in Wasserstein-2 distance (Liu et al.,2023), while dimension-independent guarantees for ULD discretizations in KL divergence have remained open. We close this gap by proving the first dimension-free KL divergence bounds for discretized ULD. Our analysis refines the KL local error framework (Altschuler et al., 2025) to a dimension-free setting and yields bounds that depend on $\mathrm{tr}(\mathbf{H})$, where $\mathbf{H}$ upper bounds the Hessian of $V$, rather than on $d$. As a consequence, we obtain improved iteration complexity for underdamped Langevin Monte Carlo relative to overdamped Langevin methods in regimes where $\mathrm{tr}(\mathbf{H})\ll d$.
Self-driving laboratories couple a learned design surrogate to an instrument, and on every new target domain it must answer four questions: when it can be trusted, how many target measurements it needs, which to make first, and when to stop adapting, switch models or escalate. We state a framework making each measurable (a competence ratio, a budget $k^*(\varepsilon)$, a time-to-target and a priced decision) and instantiate it without wet experiments on six public droplet-microfluidic and liposome tables as offline laboratories: 107 leave-one-group tiers whose rows are hidden labels. A sealed, pre-registered programme (two sealed negative validations and a pre-registered test on three more tables) and seven frozen closed-loop protocols, each run twice, yield 23 findings. Shift cost is stratified by shift type; no label-free statistic certifies individual candidates; random-split model-family rankings predicted neither the sealed nor the loop rankings. Warm-start residual boosting returns a surrogate to $1.25\times$ its development reference within 20 target rows in 94% of chemistry tiers (27% under a strict noise-floor reading), 90% of laboratory and 40% of device tiers, and a budget planned from the shift type on other tables is not measurably worse on a new one. In the loop, one gain survives drift and shuffled-label controls on all tiers, carried by the sparsely sampled ones: proposing at once and warm-starting on every measurement reaches a 10% target in 2.80 measurements against 3.31 for the reference, and in 5.72 against 11.35 for random proposals on 301 hard units at a 3% tolerance. No label-free acquisition rule survives the shuffled-label control, no interval-aware proposal or other model family does better, and no threshold rule on the tested diagnostics beats always continuing once escalation is priced. No wet-lab validation is claimed.
Machine learning models are now widely used to predict environmental variable dynamics in domains like hydrology, climate science, agriculture, and ecology. These models are usually compared on fixed benchmark datasets using a single average accuracy score. As models improve, their scores become very close when averaged over large regions and long time periods, so the benchmark can no longer tell them apart, and a single number hides \emph{where} and \emph{when} a model fails. Three failures are common across environmental domains: models get worse as the climate shifts (non-stationarity), models fail at unmonitored sites (spatial extrapolation), and models miss rare but important regimes such as floods and droughts. We present \textbf{EvoBench}, a benchmark framework that shows where a model fails, tracks failures over time, and evolves to focus on model capability gaps. We apply EvoBench to daily streamflow prediction as a case study (\textbf{CAMELS-Evolve}, about 9{,}000 U.S. basins, 1985--2024) and compare an operational physical model (NWM), a conceptual reference (HBV), and several data-driven models. No model wins on every testing scenarios (e.g., in terms of average accuracy, performance at low flows and unmonitored basins). Also we observe that all data-driven models under-predict floods. Additionally, we show that targeted fix based on the reported failures could mitigate weaknesses the benchmark identified in certain scenarios. EvoBench turns model evaluation from a saturated ranking into a moving map of model limitations.
Daogao Liu, Edith Cohen, Badih Ghazi, Peter Kairouz, Pritish Kamath, Alexander Knop, Ravi Kumar, Pasin Manurangsi 等 11 位作者
We introduce $Urania$, a novel framework for generating insights about LLM chatbot interactions with rigorous differential privacy (DP) guarantees. The framework employs a private clustering mechanism and innovative keyword extraction methods, including frequency-based, TF-IDF-based, and LLM-guided approaches. By leveraging DP tools such as clustering, partition selection, and histogram-based summarization, $Urania$ provides end-to-end privacy protection. Our evaluation assesses lexical and semantic content preservation, pair similarity, and LLM-based metrics, benchmarking against a non-private Clio-inspired pipeline (Tamkin et al., 2024). Moreover, we develop a simple empirical privacy evaluation that demonstrates the enhanced robustness of our DP pipeline. The results show the framework's ability to extract meaningful conversational insights while maintaining stringent user privacy, effectively balancing data utility with privacy preservation.