ICLR 2026 Papers

Accurate analysis of Medical time series (MedTS) data, such as Electroencephalography (EEG) and Electrocardiography (ECG), plays a pivotal role in healthcare applications, including the diagnosis of brain and heart diseases. MedTS data typically exhibits two critical patterns: **temporal dependencies** within individual channels and **channel dependencies** across multiple channels. While recent advances in deep learning have leveraged Transformer-based models to effectively capture temporal dependencies, they often struggle to model channel dependencies. This limitation stems from a structural mismatch: ***MedTS signals are inherently centralized, whereas the Transformer's attention is decentralized***, making it less effective at capturing global synchronization and unified waveform patterns. To bridge this gap, we propose **CoTAR** (Core Token Aggregation-Redistribution), a centralized MLP-based module tailored to replace the decentralized attention. Instead of allowing all tokens to interact directly, as in attention, CoTAR introduces a global core token that acts as a proxy to facilitate the inter-token interaction, thereby enforcing a centralized aggregation and redistribution strategy. This design not only better aligns with the centralized nature of MedTS signals but also reduces computational complexity from quadratic to linear. Experiments on five benchmarks validate the superiority of our method in both effectiveness and efficiency, achieving up to a **12.13%** improvement on the APAVA dataset, with merely 33% memory usage and 20% inference time compared to the previous state-of-the-art. Code and all training scripts are available in this [**Link**](https://github.com/Levi-Ackman/TeCh).

Text-to-CAD code generation is a long-horizon task, requiring the translation of instructions into a long sequence of interdependent operations. This process is exceptionally fragile, as minor early errors can propagate through the sequence and ultimately invalidate an entire complex assembly. Existing methods typically decode instructions directly into executable code (e.g., bpy) without an explicit representation of assembly hierarchy or geometric constraints. This flat decoding strategy vastly expands the search space, amplifying local errors and leading to cascading failures in contextual operations. We address this gap by learning an intermediate representation: a hierarchical and geometry-aware graph. The graph represents an assembly-based decomposition, with multi-level nodes modeling the product's parts and components, and edges defining the explicit geometric constraints between them. Rather than mapping text directly to code, our graph paradigm first predicts high-level structure and constraints, then conditions the sequencing of operations and program generation, thereby narrowing the search space and improving both geometric fidelity and constraint satisfaction. Furthermore, we introduce a structure-aware progressive curriculum learning mechanism to enhance the model's ability to generate sophisticated decomposition graphs, allowing it to handle more complex assemblies. The mechanism constructs graded tasks via controlled edits to object structure, probes the model’s capability boundary, and synthesizes boundary examples for subsequent training rounds. We also introduce a 12K-instruction dataset annotated with instructions, geometric decomposition graphs, action sequences, and bpy code, together with metrics for node- and hierarchy-level graph accuracy and a measure of constraint satisfaction. Extensive experiments show that our approach outperforms existing methods in terms of both geometric fidelity and accurate fulfillment of geometric constraints.

Biomolecular interactions play a critical role in biological processes. While recent breakthroughs like AlphaFold 3 have enabled accurate modeling of biomolecular complex structures, predicting binding affinity remains challenging mainly due to limited high-quality data. Recent methods are often specialized for specific types of biomolecular interactions, limiting their generalizability. In this work, we repurpose AlphaFold 3 for representation learning to predict binding affinity, a non-trivial task that requires shifting from generative structure prediction to encoding observed geometry, simplifying the heavily conditioned trunk module, and designing a framework to jointly capture sequence and structural information. To address these challenges, we introduce the **Atom-level Diffusion Transformer (ADiT)**, which takes sequence and structure as inputs, employs a unified tokenization scheme, integrates diffusion transformers, and removes dependencies on multiple sequence alignments and templates. We pre-train three ADiT variants on the PDB dataset with a denoising objective and evaluate them across protein-ligand, drug-target, protein-protein, and antibody-antigen interactions. The model achieves state-of-the-art or competitive performance across benchmarks, scales effectively with model size, and successfully identifies wet-lab validated affinity-enhancing antibody mutations, establishing a generalizable framework for biomolecular interactions. We plan to release the code upon acceptance.

Computed Tomography (CT) is one of the most widely used and diagnostically information-dense imaging modalities, covering critical organs such as the heart, lungs, liver, and colon. Clinical interpretation relies on both \textbf{slice-driven} local features (e.g., sub-centimeter nodules, lesion boundaries) and \textbf{volume-driven} spatial representations (e.g., tumor infiltration, inter-organ anatomical relations). However, existing Large Vision–Language Models (LVLMs) remain fragmented in CT slice versus volumetric understanding: slice-driven LVLMs show strong generalization but lack cross-slice spatial consistency, while volume-driven LVLMs explicitly capture volumetric semantics but suffer from coarse granularity and poor compatibility with slice inputs. The absence of a unified modeling paradigm constitutes a major bottleneck for the clinical translation of medical LVLMs. We present \textbf{OmniCT}, a powerful unified slice–volume LVLM for CT scans, which makes three contributions: \textbf{(i) Spatial Consistency Enhancement (SCE):} volumetric slice composition combined with tri-axial positional encoding introduces volumetric consistency, and an MoE hybird projection enables efficient slice–volume adaptation; \textbf{(ii) Organ-level Semantic Enhancement (OSE):} segmentation and ROI localization explicitly align anatomical regions, emphasizing lesion- and organ-level semantics; \textbf{(iii) MedEval-CT:} the largest slice–volume CT dataset and hybrid benchmark integrates multi-level metrics for unified evaluation. OmniCT consistently outperforms existing methods with a substantial margin across diverse clinical tasks, satisfies both micro-level detail sensitivity and macro-level spatial reasoning, and establishes a new paradigm for cross-dimensional medical imaging modeling. Our project is available at \href{https://anonymous.4open.science/r/OmniCT}{link}.

Deep spiking neural networks (SNNs) hold immense promise for low-power event-driven computing, but their direct training via backpropagation through time (BPTT) incurs prohibitive memory cost, which limits their scalability. Existing memory-saving approaches, such as online learning, BPTT-to-BP, and reversible networks, compromise accuracy, training speed, or applicability. In this work, we propose a novel and broadly applicable pipeline for memory-efficient SNN training that preserves BPTT's accuracy. Our pipeline integrates layer-wise gradient checkpointing with lossless spike compression to eliminate internal state storage and reduce the memory cost of per-layer input spikes. We also introduce a multi-stage checkpoint adjustment strategy that adaptively refines checkpoint placement based on profiling results to further optimize memory usage and improve training speed. Wrapped in an optimization pass, the pipeline automatically restructures the computation flow before training with minimal user effort. Extensive experiments on diverse architectures and tasks demonstrate up to $8\times$ memory efficiency gains with $\le 20\\%$ speed reduction and no accuracy loss. Our method provides a practical solution for efficient and scalable SNN training. Code will be available upon acceptance.

Event cameras deliver visual data with high temporal resolution, low latency, and minimal redundancy, yet their asynchronous, sparse sequential nature challenges standard tensor-based machine learning (ML). While the recent asynchronous-to-synchronous (A2S) paradigm aims to bridge this gap by asynchronously encoding events into learned features for ML pipelines, existing A2S approaches often sacrifice expressivity and generalizability compared to dense, synchronous methods. This paper introduces EVA (EVent Asynchronous feature learning), a novel A2S framework to generate highly expressive and generalizable event-by-event features. Inspired by the analogy between events and language, EVA uniquely adapts advances from language modeling in linear attention and self-supervised learning for its construction. In demonstration, EVA outperforms prior A2S methods on recognition tasks (DVS128-Gesture and N-Cars), and represents the first A2S framework to successfully master demanding detection tasks, achieving a 47.7 mAP on the Gen1 dataset. These results underscore EVA's potential for advancing real-time event-based vision applications.

Reinforcement learning in GPU-enabled physics simulation has been the driving force behind many of the breakthroughs in sim-to-real robot learning. However, current approaches for data generation in simulation are unwieldy and task-specific, requiring extensive human effort to engineer training curricula and rewards. Even with this engineering, these approaches still struggle to reliably solve long-horizon, dexterous manipulation tasks. To provide a seamless tool for robotic data generation in simulation, we introduce a simple framework that enables on-policy reinforcement learning to reliably solve an array of such tasks with a single reward function, set of algorithm hyper-parameters, no auto-curricula, and no human demonstrations. Our key insight is careful usage of diverse simulator resets for simplifying long-horizon exploration challenges. Our proposed system, OmniReset, automatically generates these resets with minimal human input and gracefully scales with compute to solve dexterous, contact-rich long-horizon tasks. OmniReset outperforms baselines on easier versions of our tasks, and scales to tasks with complexities beyond the reach of existing techniques. Finally, we use this data-generation methodology to create a large dataset of trajectories in simulation, and show that augmenting it with a small amount of real-world data enables successful real-world transfer for complex manipulation tasks.

The recognition of dynamic and social behavior in animals is fundamental for advancing several areas of the life sciences, including ethology, ecology, medicine and neuroscience. Recent progress in deep learning has enabled an automated recognition of such behavior from video data. However, an accurate reconstruction of the three-dimensional (3D) pose and shape has not been integrated into this process. Especially for non-human primates, the animals phylogenetically closest to humans, mesh-based tracking efforts lag behind those for other species, leaving pose descriptions restricted to sparse keypoints that are unable to fully capture the richness of action dynamics. To address this gap, we introduce the $\textbf{Big Ma}$ca$\textbf{Q}$ue 3D Motion and Animation Dataset ($\texttt{BigMaQ}$), a large-scale dataset comprising more than 750 scenes of interacting rhesus macaques with detailed 3D pose descriptions of skeletal joint rotations. Recordings were obtained from 16 calibrated cameras and paired with action labels derived from a curated ethogram. Extending previous surface-based animal tracking methods, we construct subject-specific textured avatars by adapting a high-quality macaque template mesh to individual monkeys. This allows us to provide pose descriptions that are more accurate than previous state-of-the-art surface-based animal tracking methods. From the original dataset, we derive BigMaQ500, an action recognition benchmark that links surface-based pose vectors to single frames across multiple individual monkeys. By pairing features extracted from established image and video encoders with and without our pose descriptors, we demonstrate substantial improvements in mean average precision (mAP) when pose information is included. With these contributions, $\texttt{BigMaQ}$ establishes the first dataset that both integrates dynamic 3D pose-shape representations into the learning task of animal action recognition and provides a rich resource to advance the study of visual appearance, posture, and social interaction in non-human primates. The code and data are publicly available at [https://martinivis.github.io/BigMaQ/](https://martinivis.github.io/BigMaQ/).

Adjuvants play a critical role in modulating immune responses and are central to the development of vaccines and immunotherapies. Yet progress in this field is constrained by data scarcity and incomplete understanding of mechanisms of action, which limit the transition from experience-based design to AI-driven approaches. To address these challenges, we present the first benchmark dedicated to adjuvants, constructed in an open-ended Q\&A format and annotated by domain experts. The benchmark comprises 1,294 Q\&A pairs and 1,364 formal descriptions, providing a resource for evaluating general-purpose multimodal large language models (MLLMs) and for developing domain-specific systems. We systematically assess 11 closed-source and 18 open-source MLLMs across dimensions including domain-specific Q\&A, hallucination rejection, data generation, and instruction following. Results indicate that OpenAI-o1 (STS = 0.7495, LLM Score = 7.7) and DeepSeek-R1 (STS = 0.7415, LLM Score = 7.7) achieved the strongest performance among closed- and open-source models, respectively. In addition, we introduce a formal description framework for representing adjuvant design principles and immune mechanisms as structured abstractions, which can serve as building blocks for future domain-specialized MLLMs. Overall, this work provides a first step toward systematically integrating MLLMs into adjuvant research by offering a dedicated benchmark, comparative evaluation of existing models, and a formal foundation for future development. Data and code will be released at \href{https://anonymous.4open.science/status/Advancing-Adjuvants-1C2B}{Anonymous}.

Pre-trained materials foundation models, or machine learning interatomic potentials, leverage general physicochemical knowledge to effectively approximate potential energy surfaces. However, they often require domain-specific calibration due to physicochemical diversity and mismatches between practical computational settings and those used in constructing the pre-training data. We propose a sparsity-promoting fine-tuning method for E(3)-equivariant materials foundation models that prune low-contribution parameters during training. Across molecular and crystalline benchmarks, our approach updates only 3 % of parameters, and in some cases as little as 0.5 %, while matching or exceeding the accuracy of full fine-tuning. Beyond energy and force calibration, we apply our method to magnetic moment prediction and magnetism-aware total energy estimation, achieving broader applicability of materials foundation models. Analysis of sparsity patterns further reveals physically interpretable signatures, such as enhanced $d$-orbital contributions in transition-metal systems. Overall, our results establish sparsity-promoting fine-tuning of equivariant models as a flexible and interpretable method for domain specialization of materials foundation models.

Many problems in trustworthy ML can be expressed as constraints on prediction rates across subpopulations, including group fairness constraints (demographic parity, equalized odds, etc.). In this work, we study such constrained minimization problems under differential privacy (DP). Standard DP optimization techniques like DP-SGD rely on objectives that decompose over individual examples, enabling per-example gradient clipping and noise addition. Rate constraints, however, depend on aggregate statistics across groups, creating inter-sample dependencies that violate this decomposability. To address this, we develop RaCO-DP, a DP variant of Stochastic Gradient Descent-Ascent (SGDA) that solves the Lagrangian formulation of rate constraint problems. We show that the additional privacy cost of incorporating these constraints reduces to privately estimating a histogram over the mini-batch at each step. We prove convergence of our algorithm through a novel analysis of SGDA that leverages the linear structure of the dual parameter. Empirical results show that our method Pareto-dominates existing private learning approaches under group fairness constraints and also achieves strong privacy–utility–fairness performance on neural networks.

Recent advances in scientific machine learning (SciML) have enabled neural operators (NOs) to serve as powerful surrogates for modeling the dynamic evolution of physical systems governed by partial differential equations (PDEs). While existing approaches focus primarily on learning simulations from the target PDE, they often overlook more fundamental physical principles underlying these equations. Inspired by how numerical solvers are compatible with simulations of different settings of PDEs, we propose a multiphysics training framework that jointly learns from both the original PDEs and their simplified basic forms. Our framework enhances data efficiency, reduces predictive errors, and improves out-of-distribution (OOD) generalization, particularly in scenarios involving shifts of physical parameters and synthetic-to-real transfer. Our method is architecture-agnostic and demonstrates consistent improvements in normalized root mean square error (nRMSE) across a wide range of 1D/2D/3D PDE problems. Through extensive experiments, we show that explicit incorporation of fundamental physics knowledge significantly strengthens the generalization ability of neural operators. We will release models and codes at https://sites.google.com/view/sciml-fundemental-pde.

Protein sequence design must balance designability, defined as the ability to recover a target backbone, with multiple, often competing, developability properties such as solubility, thermostability, and expression. Existing approaches address these properties through post hoc mutation, inference-time biasing, or retraining on property-specific subsets, yet they are target dependent and demand substantial domain expertise or careful hyperparameter tuning. In this paper, we introduce ProtAlign, a multi-objective preference alignment framework that fine-tunes pretrained inverse folding models to satisfy diverse developability objectives while preserving structural fidelity. ProtAlign employs a semi-online Direct Preference Optimization strategy with a flexible preference margin to mitigate conflicts among competing objectives and constructs preference pairs using in silico property predictors. Applied to the widely used ProteinMPNN backbone, the resulting model MoMPNN enhances developability without compromising designability across tasks including sequence design for CATH 4.3 crystal structures, de novo generated backbones, and real-world binder design scenarios, making it an appealing framework for practical protein sequence design.

Large language models (LLMs) exhibit remarkable mathematical reasoning abilities through supervised fine-tuning (SFT) or reinforcement learning with verifiable rewards (RLVR). However, adapting them to scientific domains like molecular optimization is challenging: its datasets provide only reference molecules, lacking the reasoning traces for SFT, while its competitive objectives hinder RLVR. To address these issues, we introduce Demonstration-guided Policy Optimization (DePO). We leverage reference molecules as supervised signals to regularize the search direction while preserving the model’s reasoning capabilities. Experiments show that DePO significantly outperforms both SFT and RLVR across key molecular optimization metrics, and excels in balancing the competitive optimization objectives. DePO achieves up to 13\% improvement compared to SFT and other baseline approaches. DePO also shows generalization capabilities and inference-scaling properties.

In the era of AI-driven science and engineering, we often want to design discrete objects (e.g., circuits, proteins, materials) in silico according to user-specified properties (e.g., that a protein binds its target). Given a property predictive model, in silico design typically involves training a generative model over the design space (e.g., over the set of all length-L proteins) to concentrate on designs with the desired properties. Distributional optimization, formalized as an estimation of distribution algorithm or as reinforcement learning policy optimization, maximizes an objective function in expectation over samples. Optimizing a distribution over discrete-valued designs is in general challenging due to the combinatorial nature of the design space. However, many property predictors in scientific applications are decomposable in the sense that they can be factorized over design variables in a way that will prove useful. For example, the active site amino acids in a catalytic protein may need to only loosely interact with the rest of the protein for maximal catalytic activity. Current distributional optimization algorithms are unable to make use of such structure, which could dramatically improve the optimization. Herein, we propose and demonstrate use of a new distributional optimization algorithm, Decomposition-Aware Distributional Optimization (DADO), that can leverage any decomposability defined by a junction tree on the design variables. At its core, DADO employs a factorized “search distribution”—a learned generative model—for efficient navigation of the search space, and invokes graph message passing to coordinate optimization across all variables.

Accurate prediction of the need for invasive mechanical ventilation (IMV) in intensive care units (ICUs) patients is crucial for timely interventions and resource allocation. However, variability in patient populations, clinical practices, and electronic health record (EHR) systems across institutions introduces domain shifts that degrade the generalization performance of predictive models during deployment. Test-Time Training (TTT) has emerged as a promising approach to mitigate such shifts by adapting models dynamically during inference without requiring labeled target-domain data. In this work, we introduce Adaptive Test-Time Training (AdaTTT), an enhanced TTT framework tailored for EHR-based IMV prediction in ICU settings. We begin by deriving information-theoretic bounds on the test-time prediction error and demonstrate that it is constrained by the uncertainty between the main and auxiliary tasks. To enhance their alignment, we introduce a self-supervised learning framework with pretext tasks: reconstruction and masked feature modeling optimized through a dynamic masking strategy that emphasizes features critical to the main task. Additionally, to improve robustness against domain shifts, we incorporate prototype learning and employ Partial Optimal Transport (POT) for flexible, partial feature alignment while maintaining clinically meaningful patient representations. Experiments across multi-center ICU cohorts demonstrate competitive classification performance on different test-time adaptation benchmarks.

Online learning in arbitrary and possibly adversarial environments has been extensively studied in sequential decision-making, with a strong connection to equilibrium computation in game theory. Most existing online learning algorithms are based on \emph{numeric} utility feedback from the environment, which may be unavailable in applications with humans in the loop and/or with privacy concerns. In this paper, we study an online learning setting where only a \emph{ranking} of a set of proposed actions is provided to the learning agent at each timestep. We consider both ranking models based on either the \emph{instantaneous} utility at each timestep, or the \emph{time-average} utility until the current timestep, in both \emph{full-information} and \emph{bandit} feedback settings. Focusing on the standard (external-)regret metric, we show that sublinear regret cannot be achieved with the instantaneous utility ranking feedback in general. Moreover, we show that when the ranking model is relatively {deterministic} (\emph{i.e.,} with a small temperature in the Plackett-Luce model), sublinear regret cannot be achieved with the time-average utility ranking feedback, either. We then propose new algorithms to achieve sublinear regret, under the additional assumption that the utility vectors have a sublinear variation. Notably, we also show that when time-average utility ranking is used, such an additional assumption can be avoided in the full-information setting. As a consequence, we show that if all the players follow our algorithms, an approximate coarse correlated equilibrium of a normal-form game can be found through repeated play. Finally, we also validate the effectiveness of our algorithms via numerical experiments.

We study decision making with structured observation (DMSO). The complexity for DMSO has been characterized by a series of work [ FKQR21 , CMB22 , FGH23 ]. Still, there is a gap between known regret upper and lower bounds: current upper bounds incur a model estimation error that scales with the size of the model class. The work of [FGQ+23 ] made an initial attempt to reduce the estimation error to only scale with the size of the value function set, resulting in the complexity called optimistic decision-estimation coefficient (optimistic DEC). Yet, their approach relies on the optimism principle to drive exploration, which deviates from the general idea of DEC that drives exploration only through information gain. In this work, we introduce an improved model-free DEC, called Dig-DEC, that removes the optimism mechanism in [FGQ+23 ], making it more aligned with existing model-based DEC. Dig-DEC is always upper bounded by optimistic DEC, and could be significantly smaller in special cases. Importantly, the removal of optimism allows it to seamlessly handle adversarial environments, while it was unclear how to achieve it within the optimistic DEC framework. By applying Dig-DEC to hybrid MDPs where the transition is stochastic but the reward is adversarial, we provide the first model-free regret bounds in hybrid MDPs with bandit feedback in multiple settings: bilinear classes, Bellman-complete MDPs with bounded Bellman-eluder dimension or coverability, resolving the main open problem left by [LWZ25]. We also improve online function-estimation procedure used in model-free learning: For average estimation error minimization, we improve the estimator to achieve better concentration. This improves the $T^{\frac{3}{4}}$ and $T^{\frac{5}{6}}$ regret of [FGQ+23 ] to $T^{\frac{2}{3}}$and $T^{\frac{7}{9}}$ in the cases with on-policy and off-policy exploration. For squared estimation error minimization in Bellman-complete MDPs, we redesign the two-timescale procedure in [ AZ22 , FGQ+23], achieving $\sqrt{T}$ regret that improves over the $T^{\frac{2}{3}}$ regret by [ FGQ+23 ]. This is the first time the performance of a DEC-based approach for Bellman-complete MDPs matches that of optimism-based approaches [JLM21, XFB+23].

Single-cell transcriptomics and proteomics have become a great source for data-driven insights into biology, enabling the use of advanced deep learning methods to understand cellular heterogeneity and gene expression at the single-cell level. With the advent of spatial-omics data, we have the promise of characterizing cells within their tissue context as it provides both spatial coordinates and intra-cellular transcriptional or protein counts. Beyond transcriptomics, proteomics offers a complementary view by directly measuring proteins, which are the primary effectors of cellular function and key therapeutic targets. However, existing models either ignore the spatial information or the complex genetic and proteomic programs within cells. Thus they cannot infer how cell internal regulation adapts to microenvironmental cues. Furthermore, these models often utilize fixed gene vocabularies, hindering their generalizability to datasets with different genes than pretraining. In this paper, we introduce HEIST, a hierarchical graph transformer foundation model for spatial transcriptomics and proteomics. HEIST models tissues as hierarchical graphs. The higher level graph is a spatial cell graph, and each cell in turn, is represented by its lower level gene co-expression network graph. Rather than using a fixed gene vocabulary, HEIST computes gene embeddings from its co-expression network and cellular context. HEIST achieves this by performing both intra-level and cross-level message passing to utilize the hierarchy in its embeddings and can thus generalize to novel datatypes including spatial proteomics without retraining. HEIST is pretrained on 22.3M cells from 124 tissues across 15 organs using spatially-aware contrastive and masked autoencoding objectives. Unsupervised analysis of HEIST embeddings reveals spatially informed subpopulations missed by prior models. Downstream evaluations demonstrate generalizability to proteomics data and state-of-the-art performance in clinical outcome prediction, cell type annotation, and gene imputation across multiple technologies.