NeurIPS 2026 Papers

Structure-based drug design increasingly employs LLM agents to iteratively refine ligands against a target pocket, yet a viable ligand must satisfy two often-conflicting objectives---binding affinity and druggability---which single optimization steps rarely improve together. To quantify this difficulty, we introduce two diagnostic metrics: the first measures how often a single edit improves both objectives, and the second measures how often a gain on one objective comes with a loss on the other. Applying these diagnostics to current LLM-agent pipelines exposes a consistent failure mode: the agent performs molecular editing without knowing how the pocket-ligand complex responds to local modifications, thus rarely achieving joint improvement. Inspired by medicinal chemists, who probe the pocket-ligand complex with controlled analog edits before choosing an optimization direction, we propose PROBE, an optimization framework built around edit--response probing. PROBE first decomposes the ligand into editable sites and builds a pocket-specific site map that flags where joint gains are plausible, where the two objectives are likely in tension, and where liability substructures should be changed; it then performs controlled probe edits whose responses are distilled into an EditManual. Guided by the site map and EditManual, PROBE runs an iterative multi-agent loop in which an affinity agent, a druggability agent, and a co-optimization agent jointly produce edits. On the CrossDocked2020 benchmark, PROBE achieves state-of-the-art performance and substantially mitigates the failure modes exposed by our diagnostics metrics.

Diffusion and flow-based generative models dominate visual synthesis, with guidance aligning samples to user input and improving perceptual quality. However, Classifier-Free Guidance (CFG) and extrapolation-based methods are heuristic linear combinations of velocities/scores that ignore the generative manifold geometry, breaking probability conservation and driving samples off the learned manifold under strong guidance. We analyse guidance through the continuity equation and show its effect decomposes into a divergence term and a score-parallel term defined invariantly across parameterisations. We prove the divergence term blows up structurally as sampling approaches the data manifold, motivating a time-dependent schedule alongside score-parallel attenuation. The resulting plug-and-play rule, Adaptive Manifold Guidance (AdaMaG), bounds both terms at no additional inference cost. Finally, we show that most empirical heuristics for reducing saturation or improving generation quality correspond directly to the two terms in our decomposition. Across image generation benchmarks, AdaMaG improves realism, reduces hallucinations, and induces controlled desaturation in high-guidance regimes.

Tiny Recursive Models (TRM) solve complex reasoning tasks with a fraction of the parameters of modern large language models (LLMs) by iteratively refining a latent state and final answer. While powerful, their deterministic recursion can lead to convergence at suboptimal solutions, without escape mechanism. A common workaround relies on task-specific input perturbations at test time combined with answer aggregation via voting. We introduce Probabilistic TRM (PTRM), a task-agnostic framework for test-time compute scaling that addresses this limitation through stochastic exploration. PTRM injects Gaussian noise at each deep recursion step, enabling parallel trajectories to explore diverse solution basins, and selects among them using the model’s existing Q head (used for early stopping in the original TRM). Without requiring retraining or task-specific augmentations, PTRM enables substantial accuracy gains across benchmarks, including Sudoku-Extreme (87.4% to 98.75%) and on various puzzles from Pencil Puzzle Bench (65% to 91%). On the latter, PTRM achieves nearly double the accuracy of frontier LLMs (91% vs. 55%) at less than 0.0001x the cost, using only 7M parameters.

The signature transform is a principled feature map for continuous-time paths, valued for its uniqueness and universality. Recovering a path from its truncated signature is, however, structurally ill-posed because the truncated signature map is not injective. We therefore reformulate truncated signature inversion as a probabilistic problem---learning the conditional distribution of a path given its truncated signature---and adopt a signature-conditioned flow matching model as a practical estimator. This probabilistic reformulation elucidates the fundamental difficulty of inversion: Bayes reconstruction error quantifies the irreducible uncertainty remaining after conditioning on a statistic. We derive the Bayes-optimal error under linear statistics, obtaining a closed form for log-GBM and numerically tractable formulas for log-fBM and OU---yielding a concrete theoretical baseline for model validation. This baseline upper-bounds the Bayes error under truncated-signature conditioning, since truncated signatures provide richer information than linear statistics. Experiments show that empirical reconstruction errors under linear-statistics conditioning closely match the theory-derived baseline, while errors decrease when the statistic is replaced with the truncated signature. Moreover, generated paths faithfully recover the conditioning signature while preserving key distributional and temporal structure, indicating that the estimator is well calibrated to the target conditional distribution. Together, these results establish a well-posed probabilistic framework for truncated-signature inversion, with applicability demonstrated on real financial data beyond the parametric process families covered by theory.

How should future neural reasoning systems implement extended computation? Recursive Reasoning Models (RRMs) offer a promising alternative to autoregressive sequence extension by performing iterative latent-state refinement with shared transition functions. Yet existing RRMs are largely deterministic, following a single latent trajectory and converging to a single prediction. We introduce Generative Recursive reAsoning Models (GRAM), a framework that turns recursive latent reasoning into probabilistic multi-trajectory computation. GRAM models reasoning as a stochastic latent trajectory, enabling multiple hypotheses, alternative solution strategies, and inference-time scaling through both recursive depth and parallel trajectory sampling. This yields a latent-variable generative model supporting conditional reasoning via $p_\theta(y \mid x)$ and, with fixed or absent inputs, unconditional generation via $p_\theta(x)$. Trained with amortized variational inference, GRAM improves over deterministic recurrent and recursive baselines on structured reasoning and multi-solution constraint satisfaction tasks, while demonstrating an unconditional generation capability.

Astrophysical observations from Earth are subject to weather, environmental, and scientific constraints that lead to characteristically sparse and unevenly sampled multi-wavelength time series (light curves), severely limiting the performance on downstream tasks. Interpolating light curves help in mitigating this problem, where Gaussian Processes (GPs) are the current standard. However, GPs struggle with cross-wavelength correlations, require *a priori* kernel specification, and cannot handle ensembles of diverse transient and variable classes. Furthermore, GPs and other existing models (*e.g.*, Bayesian neural networks), scale poorly and must be fit to each light curve individually, transferring no information between light curves. We introduce Attentive Neural Processes (ANPs) for light curve reconstruction, combining the probabilistic framework of GPs with the scalability of deep learning, and we demonstrate their use as a fast, data-driven, universal light curve interpolator. Unlike prior processes tailored to single object classes, our approach is morphologically agnostic. By meta-learning on a diverse population of simulated transients, ANPs shift the computation cost to the training phase, enabling amortized inference - particularly important at the eve of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST), which will produce massive datasets for transient astrophysics. We evaluate our models on realistic LSST cadences for its 6-filters across 14 transient classes. The ANP outperforms all our benchmark models, including a suite of GP and neural-network based models, on all regression quality, feature recovery, and rigorous probabilistic calibration metrics. Our ANP performs probabilistic interpolation on all filters in $\sim 10^{-6} $ seconds -- over four orders of magnitude faster than the next-best neural benchmark and over five orders of magnitude faster than GPs -- making them suitable for on-line use on the LSST alert stream estimated to carry $\sim10^{7}$ events/night. The ANP avoids neural networks' overconfidence and GPs' underconfidence, delivering sharp, highly calibrated uncertainties. This work establishes the neural process family as a scalable, probabilistic foundation for real-time transient science in the LSST era.

Patient history taking is a strategic, multi-turn process that refines diagnostic hypotheses through iterative questioning, mirroring clinical reasoning where each inquiry updates beliefs over candidate diagnoses. Deploying AI in this setting is constrained by privacy, cost, and latency, making Small Language Models (SLMs) a more desirable backbone compared to larger LLMs. However, SLMs capture only the fast, intuitive "System 1" side of this process and lack explicit mechanisms for the deliberative "System 2'' reasoning needed to maintain and update diagnostic uncertainty over time. Bayesian Networks (BayesNets) offer a natural complement, providing an interpretable framework for auditable probabilistic belief tracking. Yet, clinical BayesNets are difficult to construct due to reliance on expert-curated structure, dependencies, and parameters. We introduce ProbMedTOD, that automatically synthesizes a clinical BayesNet from a small number of clinical notes in three stages: ontology building, structure prediction, and parameter estimation. ProbMedTOD then integrates the resulting BayesNet with SLMs enabling probabilistic reasoning in multi-turn dialogues. A BayesNet Agent maintains real-time posterior distributions over diagnoses, while a Policy Agent picks the diagnostically informative questions. Experiments on DDXPlus and MIMIC-IV Notes show that ProbMedTOD outperforms LLM-only and retrieval-based baselines, with especially strong gains for smaller models.

Most LLM benchmarks score how well a model responds to explicit requests. They leave unmeasured a different conversational ability: noticing and acting on needs the user has implied but not said. We call this conversational proactivity. ProactBench decomposes it into three phase-tied types: Emergent, inference from a single disclosed anchor; Critical, synthesis across multiple anchors; and Recovery, grounded forward-looking value after task completion. We operationalise the benchmark with three agents: a Planner, a User Agent, and an Assistant Model. Their information asymmetries defend against style-confounded scoring, rubric leakage, external-context contamination, and information dumps. The released corpus contains 198 curated dialogues with 624 trigger points across 24 communication styles drawn from a psychometric inventory and audited by an independent LLM judge. Across 16 frontier and open-weight models, Recovery is both difficult and weakly predicted by six standard benchmarks, making it a useful new evaluation signal.

In real-world AI for Science scenarios, retrieval systems are increasingly expected to support experimental workflows such as experimental design and method reproduction. These workflows require retrieving protocols that satisfy a set of interdependent constraints, such as specific materials and operating conditions. However, systematic evaluation of retrievers in such multi-constraint scenarios remains lacking. To address this gap, we introduce ProSearch, a scientific retrieval benchmark for multi-constraint experimental protocol retrieval. ProSearch has three key features: (1) realism, as queries are instantiated from real method paragraphs using expert-defined experimental fields, query templates, and filtering rules; (2) complexity, involving 60 distinct fields, such as experimental subjects, materials, and operating conditions, together with dependencies among these fields; and (3) diagnosticity, as each query contains 3 to 5 explicit hard constraints and covers challenging cases such as numeric constraints and negation constraints. We construct ProSearch through LLM-based extraction, data-driven constraint selection, controlled query generation, and evidence-based relevance validation. The final benchmark contains 1,551 high-quality queries across six experimental science domains. We use ProSearch to systematically evaluate 19 representative retrievers, spanning lexical matching, general dense retrieval, scientific retrieval, and reasoning-oriented retrieval. The results reveal that current retrievers generally struggle with multi-constraint protocol retrieval, with the best-performing model achieving an average nDCG@10 of 0.290. Further constraint-wise and error analyses reveal key failure modes of existing retrievers.

Multi-modal large language models (MLLMs) with impressive perception and understanding capabilities will enable a range of downstream applications. However, their substantial computational and memory requirements hinder the real-world implementation, particularly for resources-constrained edge devices. Quantization has emerged as an effective solution for deploying large models. While post-training quantization (PTQ) successfully retrains the performance at moderate bit-width (\textit{e.g.}, W8A8), it suffers from severe performance degradation under low-bit quantization (\textit{e.g.}, W4A8/W8A8), especially for small-scale models that are more suitable for edge deployment. In this paper, we propose \texttt{ProQuant}, a novel weight-activation quantization-aware training (QAT) framework tailored for low-bit MLLMs. First, to align the limited finetuning dataset distribution with the pretrained dataset distribution, we propose a self-relabeling (SRL) scheme to resample the responses of the open-source multimodal dataset. Second, we are the \textit{first} to take a decoupled view of multi-modal (MM) understanding and language modeling abilities. We propose a progressive block activation (PBA) mechanism to prioritize the MM understanding recovery. We also introduce a vision-sensitive factor $\vec{\tau}$ that effectively identifies the MM-critical layers. Extensive experiments across various benchmarks, covering models with 2B$\sim$8B parameters, show that \texttt{ProQuant} significantly outperforms existing methods. For example, our W4A8 \texttt{Qwen3-VL-2B-Instruct} improves average accuracy by impressively 6.6\% and achieves performance comparable to full precision counterparts with only $\sim$1\% performance drop. Code will be released upon acceptance.

Feed-forward 3D foundation models have recently reshaped multi-view reconstruction, yet dynamic 4D understanding still often relies on large-scale motion supervision or hand-crafted, architecture-specific heuristics. We ask whether frozen 3D foundation model tokens already encode motion-relevant information that can be exposed by lightweight readout functions, rather than re-learning motion-specific features with high-capacity decoders. Through probing on three representative backbones, we find that static--dynamic separation is decodable from frozen token representations. Our rank-restricted and spectral analyses on $\pi^3$X reveal that the recovered motion cues are concentrated in a low-dimensional subspace. Building on this, we propose Probing-based Motion Distillation (PMD), which converts pairwise motion-state compatibility scores against a fixed anchor token into dense motion masks. Trained on only 160 YouTube-VOS videos using a single 16 GB GPU, PMD transfers zero-shot to DAVIS, SegTrackv2, and FBMS-59 without target-benchmark fine-tuning. With multi-view pretrained geometric backbones, PMD outperforms training-free heuristics and approaches substantially heavier supervised and self-supervised methods, suggesting that motion decoding from frozen 3D foundation models can be lightweight and data-efficient.

Structured visual artifacts such as geometry diagrams, circuit schematics, and flowcharts are increasingly important targets for image generation, yet visual plausibility alone is insufficient---a single missing object, wrong relation, broken connection, or extra element can invalidate the output. Existing image generators remain brittle on such tasks, and generic step-by-step or agentic methods often fail because intermediate edits may corrupt previously correct structures and ignore generator-specific failure modes. To address this, we present ProGraf, a profile-guided framework for structured non-natural image generation. We first build a benchmark of 304 tasks across geometry, circuit, flowchart, and general diagrams, each annotated with fine-grained verification points. From repeated generator outputs, we derive model-specific capability profiles capturing category-level reliability, component-level weaknesses, and recurrent failure patterns. ProGraf uses these profiles to guide closed-loop decomposition, verifies each intermediate result, commits only accepted states, and replans after failures. On generator-specific hardest subsets, ProGraf recovers 43.7--77.8\% of previously failed tasks across generators and categories, outperforming fixed-step and adapted agent baselines; ablation studies further show that benchmark-derived profiles are a key source of the gain.

Ante-hoc interpretability methods based on prototypes provide highly accurate explanations by utilizing the intuitive "this looks like that" reasoning paradigm. On the other hand, post-hoc models can explain predictions for a single image without relying on an underlying dataset or requiring costly neural network retraining. Recent approaches successfully solve the retraining problem for prototype-based networks. However, they still face a fundamental limitation: they require access to a subset of data (e.g., a test or validation set) to search for and extract the visual prototypes. In this paper, we address this issue and introduce ProDG: Data-Free Generative Prototypes for Post-Hoc Explainability, a novel framework that leverages generative models to synthesize pure, high-fidelity prototypes directly from the frozen model's weights, completely eliminating the dependency on any external data. By establishing this new frontier in Data-Free XAI, DGP unlocks robust visual interpretability for privacy-sensitive domains, where original data is strictly restricted or fundamentally inaccessible.

Time series imputation has progressed from statistical and deep learning approaches to diffusion-based models, which have shown strong recent performance. Existing diffusion-based methods typically condition the reverse process using local contextual information from the current or neighbouring windows. Meanwhile, global dataset-level structure often remains implicit, limiting performance when local observations are sparse, noisy, or unrepresentative. To address this issue, we propose ProCTI, a diffusion-imputation framework that augments local conditioning with retrieved global dataset-level priors through learned prototypes. A hybrid conditioning mechanism integrates this global context with local signals during reverse diffusion, enabling more accurate reconstruction under varying missingness scenarios. Experiments across multiple benchmark datasets show that ProCTI outperforms strong baselines overall under random missingness, while remaining competitive under attribute-wise missingness. We further introduce a theoretical framework that distinguishes between local and global conditioning in diffusion-based imputation, showing that combining both can reduce conditional uncertainty and improve imputation quality.

Real-world studies (RWS) analyze routinely collected healthcare data, such as electronic health records and insurance claims, to estimate treatment effects, monitor safety, and identify risk factors outside randomized trials. Automating RWS with large language model agents is appealing but brittle: valid analyses depend on dataset-specific clinical semantics, including index dates, follow-up windows, patient/event-level units, and outcome boundaries that are often implicit in observational data. This leads to schema mismatches, temporal errors, inconsistent analytical granularity, and unsupported clinical claims. We present ProCARE, a profile-grounded framework that reformulates RWS automation as constrained compilation. ProCARE converts heterogeneous data profiles into Evidence Contracts specifying available variables, temporal attributes, distributions, and evidentiary limits, and compiles study objectives into RWS-IR, a strongly typed intermediate representation for variables, time relations, analysis units, and statistical tasks. Deterministic validation and localized repair then check and revise generated workflows across schema mapping, cohort construction, variable derivation, analysis, and interpretation. On 36 EHR-based benchmark tasks, ProCARE outperforms strong LLM-agent baselines in code executability, semantic consistency, and conclusion traceability, with automated violation diagnoses showing moderate-to-substantial agreement with blinded expert review. Code, benchmark prompts, evaluation scripts, and the fully de-identified HCC benchmark tables are publicly available at https://anonymous.4open.science/r/ProCARE-7E52.

Aerial-Ground Person Re-Identification (AG-ReID) aims to match pedestrian images captured by unmanned aerial vehicles (UAVs) and ground-based surveillance cameras. The task remains highly challenging due to severe viewpoint discrepancies, frequent occlusions, and substantial domain gaps between aerial and ground imagery. Beyond these observable factors, existing methods often overlook two fundamental structural issues: cumulative positional drift during hierarchical feature extraction and semantic inconsistency across cross-view feature distributions. To address these challenges, we propose ProAlign, a Progressive Positional and Prototype-Guided Alignment Network for AG-ReID. ProAlign comprises two key components: a Layer-wise Progressive Positional Embedding (LPPE) module and a View-Aware Prototype Contrastive Learning (PCL) module. LPPE performs adaptive positional calibration throughout transformer layers by employing conditional positional encoding in shallow layers to mitigate local spatial distortions, while introducing learnable static positional embeddings in deeper layers to reinforce global semantic priors. Meanwhile, PCL maintains view-specific aerial and ground prototypes for each identity and enforces cross-view semantic consistency via a dual-prototype contrastive objective. Extensive experiments on the challenging CARGO benchmark demonstrate the effectiveness of ProAlign. In the aerial-ground setting, ProAlign surpasses previous state-of-the-art methods by 13.89% mAP and 9.39% Rank-1 accuracy.

Diffusion-driven image editing and regeneration are becoming increasingly widespread. This creates an urgent need for watermarking methods that can embed imperceptible yet verifiable signals into existing images for ownership attribution and provenance tracking. Existing methods fail to simultaneously satisfy three practical requirements: robustness against diffusion-based transformations, low-cost verification, and scalable support for per-user key assignment at low overhead. To address these challenges, we propose PrivateSeal, a watermarking framework for pre-existing images under diffusion-based transformations. The perturbation is encouraged to lie along low-sensitivity latent directions, so that the embedded signal is less likely to be suppressed during diffusion-based editing or regeneration. During verification, the embedded message is reliably recovered via a simple latent-space projection using the corresponding key. This design allows a platform to assign independent projection keys to different users, accounts, or images without retraining or modifying the verifier, while maintaining low-cost verification. Extensive experiments on the W-Bench benchmark show that PrivateSeal achieves competitive robustness against diffusion-based regeneration and editing, with additional cross-model and cross-dataset evaluations further validating its strong transferability.

We consider online prediction from experts, a fundamental problem in machine learning, under differential privacy constraints. Existing private algorithms achieve near-optimal regret $\tilde{O}(\sqrt{T})$, where $T$ is the time horizon. However, this bound becomes suboptimal when $L^\star$, the cumulative loss of the best expert, is significantly less than $T$. In this work, we present the first differentially private algorithm with regret $\tilde{O}(\sqrt{L^\star})$, offering a substantial improvement in the low-loss regime. Our regret bound matches the non-private lower bound up to poly-logarithmic factors, demonstrating that privacy incurs only a small cost in this setting.

Large language models (LLMs) are increasingly used to simulate human behavior, but their ability to simulate individual privacy decisions faithfully is not well understood. In this paper, we address the problem of evaluating whether a core set of user persona attributes can drive LLMs to simulate individual-level privacy behavior. We introduce PrivacySIM, an evaluation suite that benchmarks LLM simulation of user privacy behavior against the ground-truth responses of 1,000 users. These users are drawn from five published user studies on privacy spanning LLM healthcare consultations, conversational agents, and chatbots. Drawing on these user studies, we hypothesize three persona facets as plausible predictors of privacy decision-making: demographics, previous experiences with AI, and stated privacy attitudes. We condition nine frontier LLMs on subsets of these three facets and measure how often each model's response to a data-sharing scenario matches the user's actual response. Our findings show that (1) privacy persona conditioning consistently improves simulation quality over no-persona conditioning, but even the strongest model (40.4% accuracy) remains far from faithfully simulating individual privacy decisions. (2) A user's stated privacy attitudes alone may not be the best predictor as they often diverge from the user's actual privacy behavior. (3) Users with high AI experience but low stated privacy attitudes are the most challenging to simulate. PrivacySIM is a first step toward understanding and improving the capabilities of LLMs to simulate user privacy decisions.