NeurIPS 2025 Papers

The inverse folding problem, aiming to design amino acid sequences that fold into desired three-dimensional structures, is pivotal for various biotechnological applications. Here, we introduce a novel approach leveraging Direct Preference Optimization (DPO) to fine-tune an inverse folding model using feedback from a protein folding model. Given a target protein structure, we begin by sampling candidate sequences from the inverse‐folding model, then predict the three‐dimensional structure of each sequence with the folding model to generate pairwise structural‐preference labels. These labels are used to fine‐tune the inverse‐folding model under the DPO objective. Our results on the CATH 4.2 test set demonstrate that DPO fine-tuning not only improves sequence recovery of baseline models but also leads to a significant improvement in average TM-Score from 0.77 to 0.81, indicating enhanced structure similarity. Furthermore, iterative application of our DPO-based method on challenging protein structures yields substantial gains, with an average TM-Score increase of 79.5\% with regard to the baseline model. This work establishes a promising direction for enhancing protein sequence design ability from structure feedback by effectively utilizing preference optimization.

Suppressor variables can influence model predictions without being dependent on the target outcome, and they pose a significant challenge for Explainable AI (XAI) methods. These variables may cause false-positive feature attributions, undermining the utility of explanations. Although effective remedies exist for linear models, their extension to non-linear models and instance-based explanations has remained limited. We introduce PatternLocal, a novel XAI technique that addresses this gap. PatternLocal begins with a locally linear surrogate, e.g., LIME, KernelSHAP, or gradient-based methods, and transforms the resulting discriminative model weights into a generative representation, thereby suppressing the influence of suppressor variables while preserving local fidelity. In extensive hyperparameter optimization on the XAI-TRIS benchmark, PatternLocal consistently outperformed other XAI methods and reduced false-positive attributions when explaining non-linear tasks, thereby enabling more reliable and actionable insights. We further evaluate PatternLocal on an EEG motor imagery dataset, demonstrating physiologically plausible explanations.

Recent years have witnessed a surge of interest in solving combinatorial optimization problems (COPs) using machine learning techniques. Motivated by this trend, we propose a learning-augmented exact approach for tackling an NP-hard COP, the Orienteering Problem with Time Windows, which aims to maximize the total score collected by visiting a subset of vertices in a graph within their time windows. Traditional exact algorithms rely heavily on domain expertise and meticulous design, making it hard to achieve further improvements. By leveraging deep learning models to learn effective relaxations of problem restrictions from data, our approach enables significant performance gains in an exact dynamic programming algorithm. We propose a novel graph convolutional network that predicts the directed edges defining the relaxation. The network is trained in a supervised manner, using optimal solutions as high-quality labels. Experimental results demonstrate that the proposed learning-augmented algorithm outperforms the state-of-the-art exact algorithm, achieving a 38% speedup on Solomon’s benchmark and more than a sevenfold improvement on the more challenging Cordeau’s benchmark.

Interpretable reinforcement learning policies are essential for high-stakes decision-making, yet optimizing decision tree policies in Markov Decision Processes (MDPs) remains challenging. We propose SPOT, a novel method for computing decision tree policies, which formulates the optimization problem as a mixed-integer linear program (MILP). To enhance efficiency, we employ a reduced-space branch-and-bound approach that decouples the MDP dynamics from tree-structure constraints, enabling efficient parallel search. This significantly improves runtime and scalability compared to previous methods. Our approach ensures that each iteration yields the optimal decision tree. Experimental results on standard benchmarks demonstrate that SPOT achieves substantial speedup and scales to larger MDPs with a significantly higher number of states. The resulting decision tree policies are interpretable and compact, maintaining transparency without compromising performance. These results demonstrate that our approach simultaneously achieves interpretability and scalability, delivering high-quality policies an order of magnitude faster than existing approaches.

Classifier-free guidance (CFG) has become an essential component of modern diffusion models to enhance both generation quality and alignment with input conditions. However, CFG requires specific training procedures and is limited to conditional generation. To address these limitations, we propose Token Perturbation Guidance (TPG), a novel method that applies perturbation matrices directly to intermediate token representations within the diffusion network. TPG employs a norm-preserving shuffling operation to provide effective and stable guidance signals that improve generation quality without architectural changes. As a result, TPG is training-free and agnostic to input conditions, making it readily applicable to both conditional and unconditional generation. We also analyze the guidance term provided by TPG and show that its effect on sampling more closely resembles CFG compared to existing training-free guidance techniques. We extensively evaluate TPG on SDXL and Stable Diffusion 2.1, demonstrating nearly a 2x improvement in FID for unconditional generation over the SDXL baseline and showing that TPG closely matches CFG in prompt alignment. Thus, TPG represents a general, condition-agnostic guidance method that extends CFG-like benefits to a broader class of diffusion models.

Time series foundation models (TSFMs) demonstrate impressive zero-shot performance for time series forecasting. However, an important yet underexplored challenge is how to effectively finetune TSFMs on specific downstream tasks. While naive finetuning can yield performance gains, we argue that it falls short of fully leveraging TSFMs' capabilities, often resulting in overfitting and suboptimal performance. Given the diverse temporal patterns across sampling scales and the inherent multi-scale forecasting capabilities of TSFMs, we adopt a causal perspective to analyze finetuning process, through which we highlight the critical importance of explicitly modeling multiple scales and reveal the shortcomings of naive approaches. Focusing on encoder-based TSFMs, we propose Multiscale finetuning (MSFT), a simple yet general framework that explicitly integrates multi-scale modeling into the finetuning process. Experimental results on three different backbones (Moirai, Moment and Units) demonstrate that TSFMs finetuned with MSFT not only outperform naive and typical parameter efficient finetuning methods but also surpass state-of-the-art deep learning methods. Codes are available at https://github.com/zqiao11/MSFT.

As deep learning models continue to scale, the growing computational demands have amplified the need for effective coreset selection techniques. Coreset selection aims to accelerate training by identifying small, representative subsets of data that approximate the performance of the full dataset. Among various approaches, gradient-based methods stand out due to their strong theoretical underpinnings and practical benefits, particularly under limited data budgets. However, these methods face challenges such as naïve stochastic gradient descent (SGD) acting as a surprisingly strong baseline and the breakdown of representativeness due to loss curvature mismatches over time. In this work, we propose a novel framework that addresses these limitations. First, we establish a connection between posterior sampling and loss landscapes, enabling robust coreset selection even in high-data-corruption scenarios. Second, we introduce a smoothed loss function based on posterior sampling onto the model weights, enhancing stability and generalization while maintaining computational efficiency. We also present a novel convergence analysis for our sampling-based coreset selection method. Finally, through extensive experiments, we demonstrate how our approach achieves faster training and enhanced generalization across diverse datasets than the current state of the art.

Obtaining a generalizable reward model is crucial in Reinforcement Learning from Human Feedback (RLHF) as it enables correctly evaluating unseen prompt-response pairs. However, existing reward models lack this ability, as they are typically trained by increasing the reward gap between chosen and rejected responses, while overlooking the prompts that the responses are conditioned on. Consequently, when the trained reward model is evaluated on prompt-response pairs that lie outside the data distribution, neglecting the effect of prompts may result in poor generalization of the reward model. To address this issue, we decompose the reward value into two independent components: prompt-free reward and prompt-related reward. Prompt-free reward represents the evaluation that is determined only by responses, while the prompt-related reward reflects the reward that derives from both the prompt and the response. We extract these two components from an information theoretical perspective, which requires no extra models.. Subsequently, we propose a new reward learning algorithm by prioritizing data samples based on their prompt-free reward values. Through toy examples, we demonstrate that the extracted prompt-free and prompt-related rewards effectively characterize two parts of the reward model. Further, standard evaluations show that our method improves both the alignment performance and the generalization capability of the reward model.

We study online convex optimization on $\ell_p$-balls in $\mathbb{R}^d$ for $p > 2$. While always sub-linear, the optimal regret exhibits a shift between the high-dimensional setting ($d > T$), when the dimension $d$ is greater than the time horizon $T$ and the low-dimensional setting ($d \leq T$). We show that Follow-the-Regularised-Leader (FTRL) with time-varying regularisation which is adaptive to the dimension regime is anytime optimal for all dimension regimes. Motivated by this, we ask whether it is possible to obtain anytime optimality of FTRL with fixed non-adaptive regularisation. Our main result establishes that for separable regularisers, adaptivity in the regulariser is necessary, and that any fixed regulariser will be sub-optimal in one of the two dimension regimes. Finally, we provide lower bounds which rule out sub-linear regret bounds for the linear bandit problem in sufficiently high-dimension for all $\ell_p$-balls with $p \geq 1$.

Diffusion models have achieved significant success, yet their application to time series data, particularly with regard to efficient sampling, remains an active area of research. We describe an operator-learning approach for conditioned time-series diffusion models that gives efficient single-step generation by leveraging insights from the frequency-domain characteristics of both the time-series data and the diffusion process itself. The forward diffusion process induces a structured, frequency-dependent smoothing of the data's probability density function. However, this frequency smoothing is related (e.g., via likelihood function) to easily accessible frequency components of time-series data. This suggests that a module operating in the frequency space of the time-series can, potentially, more effectively learn to reverse the frequency-dependent smoothing of the data distribution induced by the diffusion process. We set up an operator learning task, based on frequency-aware building blocks, which satisfies semi-group properties, while exploiting the structure of time-series data. Evaluations on multiple datasets show that our single-step generation proposal achieves forecasting/imputation results comparable (or superior) to many multi-step diffusion schemes while significantly reducing inference costs.

One persistent challenge in LLM research is the development of attention mechanisms that are able to generalise from training on shorter contexts to inference on longer contexts. We propose two conditions that we expect all effective long-context attention mechanisms to have: scale-invariant total attention, and scale-invariant attention sparsity. Under a Gaussian assumption, we show that a simple position-dependent transformation of the attention logits is sufficient for these conditions to hold. Experimentally we find that the resulting scale-invariant attention scheme gives considerable benefits in terms of validation loss when zero-shot generalising from training on short contexts to validation on longer contexts, and is effective at long-context retrieval.

This position paper argues for two claims regarding AI testing and evaluation. First, to remain informative about deployment behaviour, evaluations need account for the possibility that AI systems understand their circumstances and reason strategically. Second, game-theoretic analysis can inform evaluation design by formalising and scrutinising the reasoning in evaluation-based safety cases. Drawing on examples from existing AI systems, a review of relevant research, and formal strategic analysis of a stylised evaluation scenario, we present evidence for these claims and motivate several research directions.

This study aims to enlarge our current knowledge on the application of brain-inspired network science principles for training artificial neural networks (ANNs) with sparse connectivity. Dynamic sparse training (DST) emulates the synaptic turnover of real brain networks, reducing the computational demands of training and inference in ANNs. However, existing DST methods face difficulties in maintaining peak performance at high connectivity sparsity levels. The Cannistraci-Hebb training (CHT) is a brain-inspired method that is used in DST for growing synaptic connectivity in sparse neural networks. CHT leverages a gradient-free, topology-driven link regrowth mechanism, which has been shown to achieve ultra-sparse (1\% connectivity or lower) advantage across various tasks compared to fully connected networks. Yet, CHT suffers two main drawbacks: (i) its time complexity is $\mathcal{O}(N\cdot d^3)$- N node network size, d node degree - hence it can be efficiently applied only to ultra-sparse networks. (ii) it rigidly selects top link prediction scores, which is inappropriate for the early training epochs, when the network topology presents many unreliable connections. Here, we design the first brain-inspired network model - termed bipartite receptive field (BRF) - to initialize the connectivity of sparse artificial neural networks. Then, we propose a matrix multiplication GPU-friendly approximation of the CH link predictor, which reduces the computational complexity to $\mathcal{O}(N^3)$, enabling a fast implementation of link prediction in large-scale models. Moreover, we introduce the Cannistraci-Hebb training soft rule (CHTs), which adopts a flexible strategy for sampling connections in both link removal and regrowth, balancing the exploration and exploitation of network topology. Additionally, we propose a sigmoid-based gradual density decay strategy, leading to an advanced framework referred to as CHTss. Empirical results show that BRF offers performance advantages over previous network science models. Using 1\% of connections, CHTs outperforms fully connected networks in MLP architectures on visual classification tasks, compressing some networks to less than 30\% of the nodes. Using 5\% of the connections, CHTss outperforms fully connected networks in two Transformer-based machine translation tasks. Finally, with only 30\% of the connections, both CHTs and CHTss achieve superior performance over other dynamic sparse training methods, and perform on par with—or even surpass—their fully connected counterparts in language modeling across various sparsity levels within the LLaMA model family. The code is available at: https://github.com/biomedical-cybernetics/Cannistraci-Hebb-training.

Preference alignment in diffusion models has primarily focused on benign human preferences (e.g., aesthetic). In this paper, we propose a novel perspective: framing unrestricted adversarial example generation as a problem of aligning with adversary preferences. Unlike benign alignment, adversarial alignment involves two inherently conflicting preferences: visual consistency and attack effectiveness, which often lead to unstable optimization and reward hacking (e.g., reducing visual quality to improve attack success). To address this, we propose APA (Adversary Preferences Alignment), a two-stage framework that decouples conflicting preferences and optimizes each with differentiable rewards. In the first stage, APA fine-tunes LoRA to improve visual consistency using rule-based similarity reward. In the second stage, APA updates either the image latent or prompt embedding based on feedback from a substitute classifier, guided by trajectory-level and step-wise rewards. To enhance black-box transferability, we further incorporate a diffusion augmentation strategy. Experiments demonstrate that APA achieves significantly better attack transferability while maintaining high visual consistency, inspiring further research to approach adversarial attacks from an alignment perspective.

Graph Transformer (GT) has recently emerged as a promising neural network architecture for learning graph-structured data. However, its global attention mechanism with quadratic complexity concerning the graph scale prevents wider application to large graphs. Effectively representing graph information while ensuring learning efficiency remains challenging, as our analysis reveals that current GT designs targeting scalability still suffer from the computational bottleneck related to graph-scale operations. In this work, we tackle the GT scalability issue by proposing HubGT, a scalable Graph Transformer boosted by fully decoupled graph processing and simplified learning. HubGT represents the graph by a novel hierarchical scheme exploiting hub labels, which is shown to be more informative than plain adjacency by offering global connections while promoting locality, and is particularly suitable for handling complex graph patterns such as heterophily. We also design algorithms for efficiently constructing and querying the hub label hierarchy tailored for the GT attention training in scalable deployments. Notably, the precomputation and training processes of HubGT achieve complexities linear to the number of graph edges and nodes, respectively, while the training stage completely removes graph-related computations, leading to favorable mini-batch capability and GPU utilization. Extensive experiments demonstrate that HubGT is efficient in terms of computational enhancement and mini-batch capability over existing GT designs on large-scale benchmarks, while achieving top-tier effectiveness on both homophilous and heterophilous graphs.

Mechanistic interpretability research seeks to reverse-engineer large language models (LLMs) by uncovering the internal representations of concepts within their activations. Sparse Autoencoders (SAEs) have emerged as a valuable tool for disentangling polysemantic neurons into more monosemantic, interpretable features. However, recent work on automatic explanation generation for these features has faced challenges: explanations tend to be overly broad and fail to take polysemanticity into consideration. This work addresses these limitations by introducing a similarity-based strategy for sourcing close negative sentences that more effectively falsify generated explanations. Additionally, we propose a structured, component-based format for feature explanations and a tree-based, iterative explanation method that refines explanations. We demonstrate that our structured format and tree-based explainer improve explanation quality, while our similarity-based evaluation strategy exposes biases in existing interpretability methods. We also analyze the evolution of feature complexity and polysemanticity across LLM layers, offering new insights into information content within LLMs' residual streams.

Multimodal large language models (MLLMs) are essential for building general-purpose AI assistants; however, they pose increasing safety risks. How can we ensure safety alignment of MLLMs to prevent undesired behaviors? Going further, it is critical to explore how to fine-tune MLLMs to preserve capabilities while meeting safety constraints. Fundamentally, this challenge can be formulated as a min-max optimization problem. However, existing datasets have not yet disentangled single preference signals into explicit safety constraints, hindering systematic investigation in this direction. Moreover, it remains an open question whether such constraints can be effectively incorporated into the optimization process for multi-modal models. In this work, we present the first exploration of the Safe RLHF-V -- the first multimodal safety alignment framework. The framework consists of: (I) BeaverTails-V, the first open-source dataset featuring dual preference annotations for helpfulness and safety, supplemented with multi-level safety labels (minor, moderate, severe); (II) Beaver-Guard-V, a multi-level guardrail system to proactively defend against unsafe queries and adversarial attacks. Applying the guard model over five rounds of filtering and regeneration significantly enhances the precursor model’s overall safety by an average of 40.9%. (II) Based on dual preference, we initiate the first exploration of multi-modal safety alignment within a constrained optimization. Experimental results demonstrate that Safe RLHF effectively improves both model helpfulness and safety. Specifically, Safe RLHF-V enhances model safety by 34.2% and helpfulness by 34.3%.

Weight-only quantization is widely used to mitigate the memory-bound nature of LLM inference. Codebook-based methods extend this trend by achieving strong accuracy in the extremely low-bit regime (e.g., 2-bit). However, current kernels rely on dequantization, which repeatedly fetches centroids and reconstructs weights, incurring substantial latency and cache pressure. We present CodeGEMM, a codebook-centric GEMM kernel that replaces dequantization with precomputed inner products between centroids and activations stored in a lightweight Psumbook. At inference, code indices directly gather these partial sums, eliminating per-element lookups and reducing the on-chip footprint. The kernel supports the systematic exploration of latency–memory–accuracy trade-offs under a unified implementation. On Llama-3 models, CodeGEMM delivers 1.83x (8B) and 8.93x (70B) speedups in the 2-bit configuration compared to state-of-the-art codebook-based quantization at comparable accuracy and further improves computing efficiency and memory subsystem utilization.

Spatial referring is a fundamental capability of embodied robots to interact with the 3D physical world. However, even with the powerful pretrained VLMs, recent approaches are still not qualified to accurately understand the complex 3D scenes and dynamically reason about the instruction-indicated locations for interaction. To this end, we propose RoboRefer, a 3D-aware vision language model (VLM) that can first achieve precise spatial understanding by integrating a disentangled but dedicated depth encoder via supervised fine-tuning (SFT). Moreover, RoboRefer advances generalized multi-step spatial reasoning via reinforcement fine-tuning (RFT), with metric-sensitive process reward functions tailored for spatial referring tasks. To support SFT and RFT training, we introduce RefSpatial, a large-scale dataset of 20M QA pairs (2x prior), covering 31 spatial relations (vs. 15 prior) and supporting complex reasoning processes (up to 5 steps). In addition, we introduce RefSpatial-Bench, a challenging benchmark filling the gap in evaluating spatial referring with multi-step reasoning. Experiments show that SFT-trained RoboRefer achieves state-of-the-art spatial understanding, with an average success rate of 89.6%. RFT-trained RoboRefer further outperforms all other baselines by a large margin, even surpassing Gemini-2.5-Pro by 12.4% in average accuracy on RefSpatial-Bench. Notably, RoboRefer can be integrated with various control policies to execute long-horizon, dynamic tasks across diverse robots (e,g., UR5, G1 humanoid) in cluttered real-world scenes.