Nature Machine Intelligence最新文献

Efficient protein structure generation with sparse denoising models 基于稀疏去噪模型的高效蛋白质结构生成

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-24 DOI: 10.1038/s42256-025-01100-z

Michael Jendrusch, Jan O. Korbel

{"title":"Efficient protein structure generation with sparse denoising models","authors":"Michael Jendrusch, Jan O. Korbel","doi":"10.1038/s42256-025-01100-z","DOIUrl":"10.1038/s42256-025-01100-z","url":null,"abstract":"Proteins play diverse roles in all domains of life and are extensively harnessed as biomolecules in biotechnology, with applications spanning from fundamental research to biomedicine. Therefore, there is considerable interest in computationally designing proteins with specified properties. Protein structure generative models provide a means to design protein structures in a controllable manner and have been successfully applied to address various protein design tasks. Such models are paired with protein sequence and structure predictors to produce and select protein sequences for experimental testing. However, current protein structure generators face important limitations for proteins with more than 400 amino acids and require retraining for protein design tasks unseen during model training. To address the first issue, we introduce salad, a family of sparse all-atom denoising models for protein structure generation. Our models are smaller and faster than the state of the art and matching or improving design quality, successfully generating structures for protein lengths up to 1,000 amino acids. To address the second issue, we combine salad with structure editing, a sampling strategy for expanding the capability of protein denoising models to unseen tasks. We apply our approach to a variety of challenging protein design tasks, from generating protein scaffolds containing functional protein motifs (motif scaffolding) to designing proteins capable of adopting multiple distinct folds under different conditions (multi-state protein design), demonstrating the flexibility of salad and structure editing. A small and fast diffusion model is presented, which is able to efficiently generate long protein backbones.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"7 9","pages":"1429-1445"},"PeriodicalIF":23.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42256-025-01100-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A multi-joint soft exosuit improves shoulder and elbow motor functions in individuals with spinal cord injury 一种多关节软外套可以改善脊髓损伤患者的肩部和肘部运动功能

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-22 DOI: 10.1038/s42256-025-01105-8

Roberto Ferroni, Gaetano D’Avola, Giorgia Sciarrone, Gabriele Righi, Claudia De Santis, Jacopo Carpaneto, Marta Gandolla, Giulio Del Popolo, Silvestro Micera, Tommaso Proietti

{"title":"A multi-joint soft exosuit improves shoulder and elbow motor functions in individuals with spinal cord injury","authors":"Roberto Ferroni, Gaetano D’Avola, Giorgia Sciarrone, Gabriele Righi, Claudia De Santis, Jacopo Carpaneto, Marta Gandolla, Giulio Del Popolo, Silvestro Micera, Tommaso Proietti","doi":"10.1038/s42256-025-01105-8","DOIUrl":"10.1038/s42256-025-01105-8","url":null,"abstract":"Spinal cord injury (SCI) disrupts neuromuscular control, severely affecting independence and quality of life. Although upper limb wearable robots hold considerable promise for functional restoration, most existing prototypes have been validated minimally in people with SCI and target almost exclusively hand opening and closing. We introduce a lightweight, modular assistive soft exosuit that simultaneously and automatically supports shoulder abduction and elbow flexion or extension movements using lightweight fabric-based pneumatic actuators, controlled through inertial sensors. The individual elbow modules were first validated in 11 healthy volunteers, and subsequently tested, together with the shoulder module, in 15 individuals with cervical SCI (C4–C7, AIS A–D). In the SCI participants, exosuits assistance resulted in increased static endurance time (by more than 250%), and lower activity of the primary muscles involved in dynamic tasks (by up to 50%). The two SCI participants retaining prehensile capability also improved their scores in the box and block test when assisted. Moreover, the soft actuation provided a safe, comfortable and easy-to-use solution that was positively appreciated by the participants. Collectively, these results provide encouraging evidence that exosuits can augment upper limb motor performance, and may ultimately translate into greater functional independence and quality of life for the SCI population. A lightweight, modular assistive soft exosuit is introduced, which supports shoulder and elbow movement in individuals with cervical spinal cord injury. The device enhances endurance and range of motion, reduces muscle effort and improves clinical test scores.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"7 9","pages":"1390-1402"},"PeriodicalIF":23.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Error-controlled non-additive interaction discovery in machine learning models 机器学习模型中误差控制的非加性交互发现

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-22 DOI: 10.1038/s42256-025-01086-8

Winston Chen, Yifan Jiang, William Stafford Noble, Yang Young Lu

{"title":"Error-controlled non-additive interaction discovery in machine learning models","authors":"Winston Chen, Yifan Jiang, William Stafford Noble, Yang Young Lu","doi":"10.1038/s42256-025-01086-8","DOIUrl":"10.1038/s42256-025-01086-8","url":null,"abstract":"Machine learning (ML) models are powerful tools for detecting complex patterns, yet their ‘black-box’ nature limits their interpretability, hindering their use in critical domains like healthcare and finance. Interpretable ML methods aim to explain how features influence model predictions but often focus on univariate feature importance, overlooking complex feature interactions. Although recent efforts extend interpretability to feature interactions, existing approaches struggle with robustness and error control, especially under data perturbations. In this study, we introduce Diamond, a method for trustworthy feature interaction discovery. Diamond uniquely integrates the model-X knockoffs framework to control the false discovery rate, ensuring a low proportion of falsely detected interactions. Diamond includes a non-additivity distillation procedure that refines existing interaction importance measures to isolate non-additive interaction effects and preserve false discovery rate control. This approach addresses the limitations of off-the-shelf interaction measures, which, when used naively, can lead to inaccurate discoveries. Diamond’s applicability spans a broad class of ML models, including deep neural networks, transformers, tree-based models and factorization-based models. Empirical evaluations on both simulated and real datasets across various biomedical studies demonstrate its utility in enabling reliable data-driven scientific discoveries. Diamond represents a significant step forward in leveraging ML for scientific innovation and hypothesis generation. Diamond, a statistically rigorous method, is capable of finding meaningful feature interactions within machine learning models, making black-box models more interpretable for science and medicine.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"7 9","pages":"1541-1554"},"PeriodicalIF":23.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42256-025-01086-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modelling neural coding in the auditory midbrain with high resolution and accuracy 高分辨率、高准确度的中脑听觉神经编码建模

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-18 DOI: 10.1038/s42256-025-01104-9

Fotios Drakopoulos, Lloyd Pellatt, Shievanie Sabesan, Yiqing Xia, Andreas Fragner, Nicholas A. Lesica

{"title":"Modelling neural coding in the auditory midbrain with high resolution and accuracy","authors":"Fotios Drakopoulos, Lloyd Pellatt, Shievanie Sabesan, Yiqing Xia, Andreas Fragner, Nicholas A. Lesica","doi":"10.1038/s42256-025-01104-9","DOIUrl":"10.1038/s42256-025-01104-9","url":null,"abstract":"Computational models of auditory processing can be valuable tools for research and technology development. Models of the cochlea are highly accurate and widely used, but models of the auditory brain lag far behind in both performance and penetration. Here we present ICNet, a convolutional encoder–decoder model of neural coding in the inferior colliculus. We developed ICNet using large-scale intracranial recordings from anaesthetized gerbils, addressing three key modelling challenges that are common across all sensory systems: capturing the full statistical structure of neuronal response patterns; accounting for physiological and experimental non-stationarity; and extracting features of sensory processing that are shared across different brains. ICNet provides highly accurate simulation of multi-unit neural responses to a wide range of complex sounds, including near-perfect responses to speech. It also reproduces key neurophysiological phenomena such as forward masking and dynamic range adaptation. ICNet can be used to simulate activity from thousands of neural units or to provide a compact representation of early central auditory processing through its latent dynamics, facilitating a wide range of hearing and audio applications. It can also serve as a foundation core, providing a baseline neural representation for models of active listening or higher-level auditory processing. Drakopoulos et al. present a model that captures the transformation from sound waves to neural activity patterns underlying early auditory processing. The model reproduces neural responses to a range of complex sounds and key neurophysiological phenomena.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"7 9","pages":"1478-1493"},"PeriodicalIF":23.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42256-025-01104-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Deep learning-based prediction of the selection factors for quantifying selection in immune receptor repertoires 作者更正：基于深度学习的选择因子预测，用于量化免疫受体库的选择

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-17 DOI: 10.1038/s42256-025-01128-1

Yuepeng Jiang, Pingping Zhang, Miaozhe Huo, Shuai Cheng Li

引用次数: 0

Aligning generalization between humans and machines 调整人类和机器之间的泛化

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-15 DOI: 10.1038/s42256-025-01109-4

Filip Ilievski, Barbara Hammer, Frank van Harmelen, Benjamin Paassen, Sascha Saralajew, Ute Schmid, Michael Biehl, Marianna Bolognesi, Xin Luna Dong, Kiril Gashteovski, Pascal Hitzler, Giuseppe Marra, Pasquale Minervini, Martin Mundt, Axel-Cyrille Ngonga Ngomo, Alessandro Oltramari, Gabriella Pasi, Zeynep G. Saribatur, Luciano Serafini, John Shawe-Taylor, Vered Shwartz, Gabriella Skitalinskaya, Clemens Stachl, Gido M. van de Ven, Thomas Villmann

{"title":"Aligning generalization between humans and machines","authors":"Filip Ilievski, Barbara Hammer, Frank van Harmelen, Benjamin Paassen, Sascha Saralajew, Ute Schmid, Michael Biehl, Marianna Bolognesi, Xin Luna Dong, Kiril Gashteovski, Pascal Hitzler, Giuseppe Marra, Pasquale Minervini, Martin Mundt, Axel-Cyrille Ngonga Ngomo, Alessandro Oltramari, Gabriella Pasi, Zeynep G. Saribatur, Luciano Serafini, John Shawe-Taylor, Vered Shwartz, Gabriella Skitalinskaya, Clemens Stachl, Gido M. van de Ven, Thomas Villmann","doi":"10.1038/s42256-025-01109-4","DOIUrl":"10.1038/s42256-025-01109-4","url":null,"abstract":"Recent advances in artificial intelligence (AI)—including generative approaches—have resulted in technology that can support humans in scientific discovery and forming decisions, but may also disrupt democracies and target individuals. The responsible use of AI and its participation in human–AI teams increasingly shows the need for AI alignment, that is, to make AI systems act according to our preferences. A crucial yet often overlooked aspect of these interactions is the different ways in which humans and machines generalize. In cognitive science, human generalization commonly involves abstraction and concept learning. By contrast, AI generalization encompasses out-of-domain generalization in machine learning, rule-based reasoning in symbolic AI, and abstraction in neurosymbolic AI. Here we combine insights from AI and cognitive science to identify key commonalities and differences across three dimensions: notions of, methods for, and evaluation of generalization. We map the different conceptualizations of generalization in AI and cognitive science along these three dimensions and consider their role for alignment in human–AI teaming. This results in interdisciplinary challenges across AI and cognitive science that must be tackled to support effective and cognitively supported alignment in human–AI teaming scenarios. Ilievski et al. examine differences and similarities in the various ways human and AI systems generalize. The insights are important for effectively supporting alignment in human–AI teams.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"7 9","pages":"1378-1389"},"PeriodicalIF":23.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Target-specific de novo design of drug candidate molecules with graph-transformer-based generative adversarial networks 基于图转换器的生成对抗网络的候选药物分子靶向从头设计

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-15 DOI: 10.1038/s42256-025-01082-y

Atabey Ünlü, Elif Çevrim, Melih Gökay Yiğit, Ahmet Sarıgün, Hayriye Çelikbilek, Osman Bayram, Deniz Cansen Kahraman, Abdurrahman Olğaç, Ahmet Sureyya Rifaioglu, Erden Banoğlu, Tunca Doğan

{"title":"Target-specific de novo design of drug candidate molecules with graph-transformer-based generative adversarial networks","authors":"Atabey Ünlü, Elif Çevrim, Melih Gökay Yiğit, Ahmet Sarıgün, Hayriye Çelikbilek, Osman Bayram, Deniz Cansen Kahraman, Abdurrahman Olğaç, Ahmet Sureyya Rifaioglu, Erden Banoğlu, Tunca Doğan","doi":"10.1038/s42256-025-01082-y","DOIUrl":"10.1038/s42256-025-01082-y","url":null,"abstract":"Discovering novel drug candidate molecules is a fundamental step in drug development. Generative deep learning models can sample new molecular structures from learned probability distributions; however, their practical use in drug discovery hinges on generating compounds tailored to a specific target molecule. Here we introduce DrugGEN, an end-to-end generative system for the de novo design of drug candidate molecules that interact with a selected protein. The proposed method represents molecules as graphs and processes them using a generative adversarial network that comprises graph transformer layers. Trained on large datasets of drug-like compounds and target-specific bioactive molecules, DrugGEN designed candidate inhibitors for AKT1, a kinase crucial in many cancers. Docking and molecular dynamics simulations suggest that the generated compounds effectively bind to AKT1, and attention maps provide insights into the model’s reasoning. Furthermore, selected de novo molecules were synthesized and shown to inhibit AKT1 at low micromolar concentrations in the context of in vitro enzymatic assays. These results demonstrate the potential of DrugGEN for designing target-specific molecules. Using the open-access DrugGEN codebase, researchers can retrain the model for other druggable proteins, provided a dataset of known bioactive molecules is available. Inhibiting AKT1 kinase can have potentially positive uses against many types of cancer. To find novel molecules targeting this protein, a graph adversarial network is trained as a generative model.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"7 9","pages":"1524-1540"},"PeriodicalIF":23.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sampling-enabled scalable manifold learning unveils the discriminative cluster structure of high-dimensional data 支持采样的可扩展流形学习揭示了高维数据的判别聚类结构

IF 23.8 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-10 DOI: 10.1038/s42256-025-01112-9

Dehua Peng, Zhipeng Gui, Wenzhang Wei, Fa Li, Jie Gui, Huayi Wu, Jianya Gong

{"title":"Sampling-enabled scalable manifold learning unveils the discriminative cluster structure of high-dimensional data","authors":"Dehua Peng, Zhipeng Gui, Wenzhang Wei, Fa Li, Jie Gui, Huayi Wu, Jianya Gong","doi":"10.1038/s42256-025-01112-9","DOIUrl":"https://doi.org/10.1038/s42256-025-01112-9","url":null,"abstract":"<p>As a pivotal branch of machine learning, manifold learning uncovers the intrinsic low-dimensional structure within complex non-linear manifolds in high-dimensional space for visualization, classification, clustering and gaining key insights. Although existing techniques have achieved remarkable successes, they suffer from extensive distortions of cluster structure, which hinders the understanding of underlying patterns. Scalability issues also limit their applicability for handling large-scale data. Here we propose a sampling-based scalable manifold learning technique that enables uniform and discriminative embedding (SUDE) for large-scale and high-dimensional data. It starts by seeking a set of landmarks to construct the low-dimensional skeleton of the entire data and then incorporates the non-landmarks into the learned space by constrained locally linear embedding. We empirically validated the effectiveness of SUDE on synthetic datasets and real-world benchmarks and applied it to analyse single-cell data and detect anomalies in electrocardiogram signals. SUDE exhibits a distinct advantage in scalability with respect to data size and embedding dimension and shows promising performance in cluster separation, integrity and global structure preservation. The experiments also demonstrate notable robustness in embedding quality as the sampling rate decreases.</p>","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":"15 1","pages":""},"PeriodicalIF":23.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"计算机科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Towards agentic science for advancing scientific discovery 走向代理科学，推进科学发现

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-10 DOI: 10.1038/s42256-025-01110-x

Hongliang Xin, John R. Kitchin, Heather J. Kulik

引用次数: 0

Real-world validation of a structure-aware pipeline for molecular design 分子设计的结构感知管道的实际验证

IF 23.9 1区计算机科学

Nature Machine Intelligence Pub Date : 2025-09-08 DOI: 10.1038/s42256-025-01102-x

Ana Laura Dias, Tiago Rodrigues

引用次数: 0