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Applications · Chemistry and Drug Discovery

Gen Zhou, Sugitha Janarthanan, Lianghong Chen, Pingzhao Hu

To address the global health threat of antimicrobial resistance, antimicrobial peptides (AMP) are being explored for their potent and promising ability to fight resistant pathogens. While artificial intelligence (AI) is being employed to advance AMP discovery and design, most AMP design models struggle to balance key goals like activity, toxicity, and novelty, using rigid or unclear scoring methods that make results hard to interpret and optimize. As the capabilities of Large Language Models (LLM) advance and evolve swiftly, we turn to AI multi-agent collaboration based on such models (multi-agent LLMs), which show rapidly rising potential in complex scientific design scenarios. Based on this, we introduce $\textbf{MAC-AMP}$, a closed-loop multi-agent collaboration (MAC) system for multi-objective AMP design. The system implements a fully autonomous simulated peer review-adaptive reinforcement learning framework that requires only a task description and example dataset to design novel AMPs. The novelty of our work lies in introducing a closed-loop multi-agent system for AMP design, with cross-domain transferability, that supports multi-objective optimization while remaining explainable rather than a 'black box'. Experiments show that MAC-AMP outperforms other AMP generative models by effectively optimizing AMP generation for multiple key molecular properties, demonstrating exceptional results in antibacterial activity, AMP likeliness, toxicity compliance, and structural reliability.

Deep Learning · Everything Else

Tianshi Zheng, Kiu Wai Tam, Kim Hue Nam Nguyen, Baixuan Xu, Zhaowei Wang, Cheng Jiayang, Hong Ting Tsang, Weiqi Wang, Jiaxin Bai, Tianqing Fang 等

Large language models (LLMs) are emerging as powerful tools for scientific law discovery, a foundational challenge in AI-driven science. However, existing benchmarks for this task suffer from a fundamental methodological trilemma, forcing a trade-off between scientific relevance, scalability, and resistance to memorization. Furthermore, they oversimplify discovery as static function fitting, failing to capture the authentic scientific process of uncovering embedded laws through the interactive exploration of complex model systems. To address these critical gaps, we introduce **NewtonBench**, a benchmark comprising 324 scientific law discovery tasks across 12 physics domains. Our design mitigates the evaluation trilemma by using counterfactual law shifts - systematic alterations of canonical laws - to generate a vast suite of problems that are scalable, scientifically relevant, and memorization-resistant. Moreover, we elevate the evaluation from static function fitting to interactive model discovery, requiring agents to experimentally probe simulated complex systems to uncover hidden principles. Our extensive evaluation of 11 state-of-the-art LLMs reveals a clear but fragile capability for discovery in frontier models: this ability degrades precipitously with increasing system complexity and exhibits extreme sensitivity to observational noise. Notably, we uncover a paradoxical effect of tool assistance: providing a code interpreter can hinder more capable models by inducing a premature shift from exploration to exploitation, causing them to satisfice on suboptimal solutions. These results demonstrate that robust, generalizable discovery in complex, interactive environments remains the core challenge for the future of automated science. By providing a scalable, robust, and scientifically authentic testbed, NewtonBench offers a crucial tool for measuring true progress and guiding the development of next-generation AI agents capable of genuine scientific discovery.

Computer Vision · 3D Rendering & Reconstruction

Jonas Belouadi, Tamy Boubekeur, Adrien Kaiser

Material node graphs are programs that generate the 2D channels of procedural materials, including geometry such as roughness and displacement maps, and reflectance such as albedo and conductivity maps. They are essential in computer graphics for representing the appearance of virtual 3D objects parametrically and at arbitrary resolution. In particular, their directed acyclic graph structure and intermediate states enable a modular, interpretable workflow for interactive appearance modeling. However, creating such graphs remains challenging and typically requires professional training. While recent neural program synthesis approaches attempt to simplify this process, they solely represent graphs as textual programs, failing to capture the inherently visual-spatial nature of node graphs that makes them accessible to humans. To address this gap, we present MultiMat, a multimodal program synthesis framework that leverages large multimodal models to process both visual and textual graph representations for improved generation of procedural material graphs. We train our models on a new dataset of production-quality procedural materials and combine them with a constrained tree search inference algorithm that ensures static correctness while efficiently navigating the program space. Our experimental results show that our multimodal program synthesis method is more efficient in both unconditional and conditional graph synthesis with higher visual quality and fidelity than text-only baselines, establishing new state-of-the-art performance.

General Machine Learning · Transfer, Multitask and Meta-learning

Hong Ye Tan, Emma Slade

Dataset distillation aims to find a small synthetic training set, such that training on the synthetic data achieves similar performance to training on a larger training dataset. Early methods solve this by interpreting the distillation problem as a bi-level optimization problem. On the other hand, disentangled methods bypass pixel-space optimization by matching data distributions and using generative techniques, leading to better computational complexity in terms of size of both training and distilled datasets. We demonstrate that by using latent spaces, the empirically successful disentangled methods can be reformulated as an optimal quantization problem, where a finite set of points is found to approximate the underlying probability measure. In particular, we link disentangled dataset distillation methods to the classical problem of optimal quantization, and are the first to demonstrate consistency of distilled datasets for diffusion-based generative priors. We propose Dataset Distillation by Optimal Quantization (DDOQ), based on clustering in the latent space of latent diffusion models. Compared to a similar clustering method D4M, we achieve better performance and inter-model generalization on the ImageNet-1K dataset using the same model and with trivial additional computation, achieving SOTA performance in higher image-per-class settings. Using the distilled noise initializations in a stronger diffusion transformer model, we obtain competitive or SOTA distillation performance on ImageNet-1K and its subsets, outperforming recent diffusion guidance methods.

Theory · Interpretability and Visualization

Jingyi Cui, Qi Zhang, Yifei Wang, Yisen Wang

Sparse autoencoders (SAEs) have recently emerged as a powerful tool for interpreting the features learned by large language models (LLMs). By reconstructing features with sparsely activated networks, SAEs aim to recover complex superposed polysemantic features into interpretable monosemantic ones. Despite their wide applications, it remains unclear under what conditions SAEs can fully recover the ground truth monosemantic features from the superposed polysemantic ones. In this paper, we provide the first theoretical analysis with a closed-form solution for SAEs, revealing that they generally fail to fully recover the ground truth monosemantic features unless the ground truth features are extremely sparse. To improve the feature recovery of SAEs in general cases, we propose a reweighting strategy targeting at enhancing the reconstruction of the ground truth monosemantic features instead of the observed polysemantic ones. We further establish a theoretical weight selection principle for our proposed weighted SAE (WSAE). Experiments across multiple settings validate our theoretical findings and demonstrate that our WSAE significantly improves feature monosemanticity and interpretability.

Social Aspects · Accountability, Transparency and Interpretability

Qi Zhang, Yifei Wang, Xiaohan Wang, Jiajun Chai, Guojun Yin, Wei Lin, Yisen Wang

In recent years, pre-trained large language models have achieved remarkable success across diverse tasks. Besides the pivotal role of self-supervised pre-training, their effectiveness in downstream applications also depends critically on the post-training process, which adapts models to task-specific data and objectives. However, this process inevitably introduces model shifts that can influence performance in different domains, and how such shifts transfer remains poorly understood. To open up the black box, we propose the SAE-based Transferability Score (STS), a new metric that leverages sparse autoencoders (SAEs) to forecast post-training transferability. Taking supervised fine-tuning as an example, STS identifies shifted dimensions in SAE representations and calculates their correlations with downstream domains, enabling reliable estimation of transferability \textit{before} fine-tuning. Extensive experiments across multiple models and domains show that STS accurately predicts the transferability of supervised fine-tuning, achieving Pearson correlation coefficients above 0.7 with actual performance changes. Beyond this, we take an initial step toward extending STS to reinforcement learning. We believe that STS can serve as an {\color{black} interpretable} tool for guiding post-training strategies in LLMs. Code is available at \url{https://github.com/PKU-ML/STS}.

Social Aspects · Privacy-preserving Statistics and Machine Learning

Gauri Pradhan, Joonas Jälkö, Santiago Zanella-Beguelin, Antti Honkela

Training machine learning models with differential privacy (DP) limits an adversary's ability to infer sensitive information about the training data. It can be interpreted as a bound on the adversary's capability to distinguish two adjacent datasets according to the chosen adjacency relation. In practice, most DP implementations use the add/remove adjacency relation, where two datasets are adjacent if one can be obtained from the other by adding or removing a single record, thereby protecting membership. In many ML applications, however, the goal is to protect attributes of individual records (e.g., labels used in supervised fine-tuning). We show that privacy accounting under add/remove overstates attribute privacy compared to accounting under the substitute adjacency relation, which permits substituting one record. To demonstrate this gap, we develop novel attacks to audit DP under substitute adjacency, and show empirically that audit results are inconsistent with DP guarantees reported under add/remove, yet remain consistent with the budget accounted under the substitute adjacency relation. Our results highlight that the choice of adjacency when reporting DP guarantees is critical when the protection target is per-record attributes rather than membership.

Applications · Chemistry and Drug Discovery

Yuanpeng Zhang, Zhijian Huang, Ziyu Fan, Siyuan Shen, Yahan Li, Shangqian Wu, Min Wu, Lei Deng

Cancer treatment efficacy exhibits high inter-patient heterogeneity due to genomic variations. While large-scale in vitro drug response data from cancer cell lines exist, predicting patient drug responses remains challenging due to genomic distribution shifts and the scarcity of clinical response data. Existing transfer learning methods primarily align global genomic features between cell lines and patients. However, they often ignore two critical aspects. First, drug response depends on specific drug substructures and genomic pathways. Second, drug response mechanisms differ in vitro and in vivo settings due to factors such as the immune system and tumor microenvironment. To address these limitations, we propose DeepSADR, a novel deep transfer learning framework for enhanced drug response prediction based on subsequence interaction and adaptive readout. In particular, DeepSADR models drug responses as interpretable bipartite interaction graphs between drug substructures and enriched genomic pathways. Subsequently, a supervised graph autoencoder was designed to capture latent interactions between drugs and gene subsequences within these interaction graphs. In addition, DeepSADR treats the drug response process as a transferable domain. A Set Transformer-based adaptive readout (AR) function learns domain-invariant response representations, enabling effective knowledge transfer from abundant cell line data to scarce patient data. Extensive experiments on clinical patient cohorts demonstrate that DeepSADR significantly outperforms state-of-the-art methods, and ablation experiments have validated the effectiveness of each module.

General Machine Learning · Representation Learning

Despoina Touska, Bastiaan Auer, Alexandru Onose, Tejaswi Kasarla, Luis Armando Pérez Rey, Maximilian Lipp, Lyubov Amitonova, Martin R. Oswald, Pascal Cerfontaine

Neural synchrony is hypothesized to help the brain organize visual scenes into structured multi-object representations. In machine learning, synchrony-based models analogously learn object-centric representations by storing binding in the phase of complex-valued features. Rotating Features (RF) instantiate this idea with vector-valued activations, encoding object presence in magnitudes and affiliation in orientations. We propose Orthogonal Rotating Features (OrthoRF), which enforces orthogonality in RF’s orientation space via an inner-product loss and architectural modifications. This yields sharper phase alignment and more reliable grouping. In evaluations of unsupervised object discovery, including settings with overlapping objects, noise, and out-of-distribution tests, OrthoRF matches or outperforms current models while producing more interpretable representations, and it eliminates the post-hoc clustering required by many synchrony-based approaches. Unlike current models, OrthoRF also recovers occluded object parts, indicating stronger grouping under occlusion. Overall, orthogonality emerges as a simple, effective inductive bias for synchrony-based object-centric learning.

Theory · Reinforcement Learning and Planning

Donghwan Lee, Hyukjun Yang, Bumgeun Park

There are two primary approaches to solving Markov decision problems (MDPs): dynamic programming based on the Bellman equation and linear programming (LP). Dynamic programming methods are the most widely used and form the foundation of both classical and modern reinforcement learning (RL). By contrast, LP-based methods have been less commonly employed, although they have recently gained attention in contexts such as offline RL. The relative underuse of the LP-based methods stems from the fact that it leads to an inequality-constrained optimization problem, which is generally more challenging to solve effectively compared with Bellman-equation-based methods. The purpose of this paper is to establish a theoretical foundation for solving LP-based MDPs in a more effective and practical manner. Our key idea is to leverage the log-barrier function, widely used in inequality-constrained optimization, to transform the LP formulation of the MDP into an unconstrained optimization problem. This reformulation enables approximate solutions to be obtained easily via gradient descent. While the method may appear naive, to the best of our knowledge, a thorough theoretical interpretation of this approach has not yet been developed. This paper aims to bridge this gap.

Computer Vision · Vision Models & Multimodal

Xintong Li, Chuhan Wang, Junda Wu, Rohan Surana, Tong Yu, Julian McAuley, Jingbo Shang

Direct Preference Optimization (DPO) has recently been extended from text-only models to vision-language models. However, existing methods rely on oversimplified pairwise comparisons, generating a single negative image via basic perturbations or similarity-based retrieval, which fail to capture the complex nature of multimodal preferences, inducing optimization bias and hallucinations. To address this issue, we propose MISP-DPO, the first framework to incorporate \emph{multiple}, semantically \emph{diverse} negative images in multimodal DPO via the Plackett-Luce model. Our method embeds prompts and candidate images in CLIP (Contrastive Language–Image Pre-training) space and applies a sparse autoencoder to uncover semantic deviations into interpretable factors. Negative samples are selected based on reconstruction difficulty, semantic deviation from the positive, and mutual diversity, yielding broader and more informative supervision. To handle multi-negative comparisons, we adopt a Plackett–Luce objective and introduce an importance sampling strategy that improves training efficiency. Experiments across five diverse benchmarks demonstrate that MISP-DPO consistently improves multimodal alignment over prior methods, validating the effectiveness of semantic-aware, multi-negative sampling in preference-based learning.

Social Aspects · Accountability, Transparency and Interpretability

Taisei Yamamoto, Ryoma Kumon, Danushka Bollegala, Hitomi Yanaka

As large language models (LLMs) are increasingly deployed worldwide, ensuring their fair and comprehensive cultural understanding is important. However, LLMs exhibit cultural bias and limited awareness of underrepresented cultures, while the mechanisms underlying their cultural understanding remain underexplored. To fill this gap, we conduct a neuron-level analysis to identify neurons that drive cultural behavior, introducing a gradient-based scoring method with additional filtering for precise refinement. We identify culture-general neurons contributing to cultural understanding regardless of cultures, and culture-specific neurons tied to an individual culture. Culture-general and culture-specific neurons account for less than 1% of all neurons and are concentrated in shallow to middle MLP layers. We validate their role by showing that suppressing them substantially degrades performance on cultural benchmarks (by up to 30%), while performance on general natural language understanding (NLU) benchmarks remains largely unaffected. Moreover, we show that culture-specific neurons support knowledge of not only the target culture, but also related cultures. Finally, we demonstrate that training on NLU benchmarks can diminish models' cultural understanding when we update modules containing many culture-general neurons. These findings provide insights into the internal mechanisms of LLMs and offer practical guidance for model training and engineering. Our code is available at https://github.com/ynklab/CULNIG

General Machine Learning · Representation Learning

Daiki Yoshikawa, Takashi Matsubara

Vision-language models have achieved remarkable success in multi-modal representation learning from large-scale pairs of visual scenes and linguistic descriptions. However, they still struggle to simultaneously express two distinct types of semantic structures: the hierarchy within a concept family (e.g., *dog* $\preceq$ *mammal* $\preceq$ *animal*) and the compositionality across different concept families (e.g., "a dog in a car" $\preceq$ *dog*, *car*). Recent works have addressed this challenge by employing hyperbolic space, which efficiently captures tree-like hierarchy, yet its suitability for representing compositionality remains unclear. To resolve this dilemma, we propose *PHyCLIP*, which employs an $\ell_1$-*P*roduct metric on a Cartesian product of *Hy*perbolic factors. With our design, intra-family hierarchies emerge within individual hyperbolic factors, and cross-family composition is captured by the $\ell_1$-product metric, analogous to a Boolean algebra. Experiments on zero-shot classification, retrieval, hierarchical classification, and compositional understanding tasks demonstrate that PHyCLIP outperforms existing single-space approaches and offers more interpretable structures in the embedding space.

General Machine Learning · Representation Learning

Zijing Zhang, Ziyang Chen, Mingxiao Li, Zhaopeng Tu, Xiaolong Li

The development of autonomous agents for complex, long-horizon tasks is a central goal in AI. However, dominant training paradigms face a critical limitation: reinforcement learning (RL) methods that optimize solely for final task success often reinforce flawed or inefficient reasoning paths, a problem we term inefficient exploration. This leads to agents that are brittle and fail to generalize, as they learn to find solutions without learning how to reason coherently. To address this, we introduce RLVMR, a novel frame-work that integrates dense, process-level supervision into end-to-end RL by rewarding verifiable, meta-reasoning behaviors. RLVMR equips an agent to explicitly tag its cognitive steps—such as planning, exploration, and reflection—and provides program-matic, rule-based rewards for actions that contribute to effective problem-solving. These process-centric rewards are combined with the final outcome signal and optimized using a critic-free policy gradient method. On the challenging ALFWorld and ScienceWorld benchmarks, RLVMR achieves new state-of-the-art results, with our 7B model reaching an 83.6% success rate on the most difficult unseen task split. Our analysis confirms these gains stem from improved reasoning quality, including significant reductions in redundant actions and enhanced error recovery, leading to more robust, efficient, and interpretable agents.

Siyu Chen, Heejune Sheen, Xuyuan Xiong, Tianhao Wang, Zhuoran Yang

We study the challenge of achieving theoretically grounded feature recovery using Sparse Autoencoders (SAEs) for the interpretation of Large Language Models. Existing SAE training algorithms often lack rigorous mathematical guarantees and suffer from practical limitations such as hyperparameter sensitivity and instability. We rethink this problem from the perspective of neuron activation frequencies, and through controlled experiments, we identify a striking phenomenon we term neuron resonance: neurons reliably learn monosemantic features when their activation frequency matches the feature's occurrence frequency in the data. Building on this finding, we introduce a new SAE training algorithm based on ``bias adaptation'', a technique that adaptively adjusts neural network bias parameters to ensure appropriate activation sparsity. We theoretically prove that this algorithm correctly recovers all monosemantic features when input data is sampled from our proposed statistical model. Furthermore, we develop an improved empirical variant, Group Bias Adaptation (GBA), and demonstrate its superior performance against benchmark methods when applied to LLMs with up to 2 billion parameters. This work represents a foundational step in demystifying SAE training by providing the first SAE algorithm with theoretical recovery guarantees and practical effectiveness for LLM interpretation.

Applications · Chemistry and Drug Discovery

Heewoong Noh, Namkyeong Lee, Gyoung S. Na, Kibum Kim, Chanyoung Park

Spectral analysis provides crucial clues for the elucidation of unknown materials. Among various techniques, infrared spectroscopy (IR) plays an important role in laboratory settings due to its high accessibility and low cost. However, existing approaches often fail to reflect expert analytical processes and lack flexibility in incorporating diverse types of chemical knowledge, which is essential in real-world analytical scenarios. In this paper, we propose IR-Agent, a novel multi-agent framework for molecular structure elucidation from IR spectra. The framework is designed to emulate expert-driven IR analysis procedures and is inherently extensible. Each agent specializes in a specific aspect of IR interpretation, and their complementary roles enable integrated reasoning, thereby improving the overall accuracy of structure elucidation. Through extensive experiments, we demonstrate that IR-Agent not only improves baseline performance on experimental IR spectra but also shows strong adaptability to various forms of chemical information. The source code for IR-Agent is available at https://github.com/HeewoongNoh/IR-Agent.

General Machine Learning · Representation Learning

Ya Wen, Jixuan Cai, Qiyao Ma, Linyan Li, Xinhuan Chen, Chris Webster, Yulun Zhou

Representation learning of geospatial locations remains a core challenge in achieving general geospatial intelligence, with increasingly diverging philosophies and techniques. While Earth observation paradigms excel at depicting locations in their physical states, we propose that a location’s full characterization requires grounding in both its physical attributes and its internal human activity pattern, the latter being particularly crucial for understanding its human-centric functions. We present MoRA, a human-centric geospatial framework that leverages a mobility graph as its core backbone to fuse various data modalities, aiming to learn embeddings that represent the socio-economic context and functional role of a location. MoRA achieves this through the integration of spatial tokenization, GNNs, and asymmetric contrastive learning to align 100M+ POIs, massive remote sensing imagery, and structured demographic statistics with a billion-edge mobility graph, ensuring the three auxiliary modalities are interpreted through the lens of fundamental human dynamics. To rigorously evaluate the effectiveness of MoRA, we construct a benchmark dataset composed of 9 downstream prediction tasks across social and economic domains. Experiments show that MoRA, with four input modalities and a compact 128-dimensional representation space, achieves superior predictive performances than state-of-the-art models by an average of 12.9\%. Echoing LLM scaling laws, we further demonstrate the scaling behavior in geospatial representation learning. We open-source code and pretrained models at: https://github.com/ylzhouchris/MoRA.

Applications · Physics

Darya Biparva, Maarten Schoukens, Donatello Materassi

State-of-the-art machine learning models often incorporate prior knowledge or structural information about the task or data distribution. In some tasks, such knowledge may arise from first principles or emerge as simplified, learned functions that distill essential aspects of the data distribution. Model augmentation has emerged as a strategy to leverage this structured knowledge by coupling it with an auxiliary model to improve predictive performance, while preserving the interpretability offered by the simpler component. In this work, we present a new augmentation framework called the Tutor-Pupil scheme, which is designed to enhance both performance and interpretability. The Pupil is a fixed model, structurally designed for the core task, while the Tutor is a more flexible model trained to apply minimal input-level corrections to improve the Pupil’s performance on the modified input. This strict separation of roles enables the Tutor not only to compensate for the Pupil’s limitations but also to act as a diagnostic instrument. By examining the Tutor’s targeted interventions, we can identify failure modes, detect regions where the Pupil struggles to generalize, and uncover residual patterns or higher-order structures in the data not captured by the original model.

Optimization · Sampling and Optimization

Soumya Ram, Akhila Ram

Sampling from trained predictors is fundamental for interpretability and as a compute-light alternative to diffusion models, but local samplers struggle on the rugged, high-frequency functions such models learn. We observe that standard neural‑network training implicitly produces a coarse‑to‑fine sequence of models. Early checkpoints suppress high‑degree/ high‑frequency components (Boolean monomials; spherical harmonics under NTK), while later checkpoints restore detail. We exploit this by running a simple annealed sampler across the training trajectory, using early checkpoints for high‑mobility proposals and later ones for refinement. In the Boolean domain, this can turn the exponential bottleneck arising from rugged landscapes or needle gadgets into a near-linear one. In the continuous domain, under the NTK regime, this corresponds to smoothing under the NTK kernel. Requiring no additional compute, our method shows strong empirical gains across a variety of synthetic and real-world tasks, including constrained sampling tasks that diffusion models are unable to handle.

Applications · Neuroscience, Cognitive Science

Badr AlKhamissi, C. De Sabbata, Greta Tuckute, Zeming Chen, Martin Schrimpf, Antoine Bosselut

Human cognitive behavior arises from the interaction of specialized brain networks dedicated to distinct functions, such as language, logic, and social reasoning. Inspired by this organization, we propose Mixture of Cognitive Reasoners (MiCRo): a modular, transformer-based architecture post-trained with a curriculum that induces functional specialization across experts. Concretely, we partition the layers of a pretrained language model into four expert modules aligned with well-studied cognitive networks in the human brain. MiCRo offers three key advantages over standard language models. (1) The specialized experts are interpretable and causally meaningful---ablating a module causes substantial drops on benchmarks requiring its specialized domain. (2) MiCRo's behavior can be dynamically steered at inference time by routing tokens to particular experts (e.g., favoring social over logical reasoning), enabling fine-grained control over outputs. (3) MiCRo outperforms or matches comparable baselines on both machine-learning reasoning benchmarks (e.g., GSM8K, BBH) and alignment to human behavior (CogBench), while maintaining interpretability. Taken together, cognitively grounded functional specialization yields models that are both more human-like and more human-interpretable.