Nature Machine Intelligence最新文献

{"title":"Learning motif-based graphs for drug–drug interaction prediction via local–global self-attention","authors":"Yi Zhong, Gaozheng Li, Ji Yang, Houbing Zheng, Yongqiang Yu, Jiheng Zhang, Heng Luo, Biao Wang, Zuquan Weng","doi":"10.1038/s42256-024-00888-6","DOIUrl":"https://doi.org/10.1038/s42256-024-00888-6","url":null,"abstract":"<p>Unexpected drug–drug interactions (DDIs) are important issues for both pharmaceutical research and clinical applications due to the high risk of causing severe adverse drug reactions or drug withdrawals. Many deep learning models have achieved high performance in DDI prediction, but model interpretability to reveal the underlying causes of DDIs has not been extensively explored. Here we propose MeTDDI—a deep learning framework with local–global self-attention and co-attention to learn motif-based graphs for DDI prediction. MeTDDI achieved competitive performance compared with state-of-the-art models. Regarding interpretability, we conducted extensive assessments on 73 drugs with 13,786 DDIs and MeTDDI can precisely explain the structural mechanisms for 5,602 DDIs involving 58 drugs. Besides, MeTDDI shows potential to explain complex DDI mechanisms and mitigate DDI risks. To summarize, MeTDDI provides a new perspective on exploring DDI mechanisms, which will benefit both drug discovery and polypharmacy for safer therapies for patients.</p>","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":23.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085189","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}

{"title":"A deep learning method that identifies cellular heterogeneity using nanoscale nuclear features","authors":"Davide Carnevali, Limei Zhong, Esther González-Almela, Carlotta Viana, Mikhail Rotkevich, Aiping Wang, Daniel Franco-Barranco, Aitor Gonzalez-Marfil, Maria Victoria Neguembor, Alvaro Castells-Garcia, Ignacio Arganda-Carreras, Maria Pia Cosma","doi":"10.1038/s42256-024-00883-x","DOIUrl":"https://doi.org/10.1038/s42256-024-00883-x","url":null,"abstract":"<p>Cellular phenotypic heterogeneity is an important hallmark of many biological processes and understanding its origins remains a substantial challenge. This heterogeneity often reflects variations in the chromatin structure, influenced by factors such as viral infections and cancer, which dramatically reshape the cellular landscape. To address the challenge of identifying distinct cell states, we developed artificial intelligence of the nucleus (AINU), a deep learning method that can identify specific nuclear signatures at the nanoscale resolution. AINU can distinguish different cell states based on the spatial arrangement of core histone H3, RNA polymerase II or DNA from super-resolution microscopy images. With only a small number of images as the training data, AINU correctly identifies human somatic cells, human-induced pluripotent stem cells, very early stage infected cells transduced with DNA herpes simplex virus type 1 and even cancer cells after appropriate retraining. Finally, using AI interpretability methods, we find that the RNA polymerase II localizations in the nucleoli aid in distinguishing human-induced pluripotent stem cells from their somatic cells. Overall, AINU coupled with super-resolution microscopy of nuclear structures provides a robust tool for the precise detection of cellular heterogeneity, with considerable potential for advancing diagnostics and therapies in regenerative medicine, virology and cancer biology.</p>","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":23.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085188","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}

{"title":"Factuality challenges in the era of large language models and opportunities for fact-checking","authors":"Isabelle Augenstein,&nbsp;Timothy Baldwin,&nbsp;Meeyoung Cha,&nbsp;Tanmoy Chakraborty,&nbsp;Giovanni Luca Ciampaglia,&nbsp;David Corney,&nbsp;Renee DiResta,&nbsp;Emilio Ferrara,&nbsp;Scott Hale,&nbsp;Alon Halevy,&nbsp;Eduard Hovy,&nbsp;Heng Ji,&nbsp;Filippo Menczer,&nbsp;Ruben Miguez,&nbsp;Preslav Nakov,&nbsp;Dietram Scheufele,&nbsp;Shivam Sharma,&nbsp;Giovanni Zagni","doi":"10.1038/s42256-024-00881-z","DOIUrl":"10.1038/s42256-024-00881-z","url":null,"abstract":"The emergence of tools based on large language models (LLMs), such as OpenAI’s ChatGPT and Google’s Gemini, has garnered immense public attention owing to their advanced natural language generation capabilities. These remarkably natural-sounding tools have the potential to be highly useful for various tasks. However, they also tend to produce false, erroneous or misleading content—commonly referred to as hallucinations. Moreover, LLMs can be misused to generate convincing, yet false, content and profiles on a large scale, posing a substantial societal challenge by potentially deceiving users and spreading inaccurate information. This makes fact-checking increasingly important. Despite their issues with factual accuracy, LLMs have shown proficiency in various subtasks that support fact-checking, which is essential to ensure factually accurate responses. In light of these concerns, we explore issues related to factuality in LLMs and their impact on fact-checking. We identify key challenges, imminent threats and possible solutions to these factuality issues. We also thoroughly examine these challenges, existing solutions and potential prospects for fact-checking. By analysing the factuality constraints within LLMs and their impact on fact-checking, we aim to contribute to a path towards maintaining accuracy at a time of confluence of generative artificial intelligence and misinformation. Large language models (LLMs) present challenges, including a tendency to produce false or misleading content and the potential to create misinformation or disinformation. Augenstein and colleagues explore issues related to factuality in LLMs and their impact on fact-checking.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142022075","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}

{"title":"A bioactivity foundation model using pairwise meta-learning","authors":"Bin Feng,&nbsp;Zequn Liu,&nbsp;Nanlan Huang,&nbsp;Zhiping Xiao,&nbsp;Haomiao Zhang,&nbsp;Srbuhi Mirzoyan,&nbsp;Hanwen Xu,&nbsp;Jiaran Hao,&nbsp;Yinghui Xu,&nbsp;Ming Zhang,&nbsp;Sheng Wang","doi":"10.1038/s42256-024-00876-w","DOIUrl":"10.1038/s42256-024-00876-w","url":null,"abstract":"The bioactivity of compounds plays an important role in drug development and discovery. Existing machine learning approaches have poor generalizability in bioactivity prediction due to the small number of compounds in each assay and incompatible measurements among assays. In this paper, we propose ActFound, a bioactivity foundation model trained on 1.6 million experimentally measured bioactivities and 35,644 assays from ChEMBL. The key idea of ActFound is to use pairwise learning to learn the relative bioactivity differences between two compounds within the same assay to circumvent the incompatibility among assays. ActFound further exploits meta-learning to jointly optimize the model from all assays. On six real-world bioactivity datasets, ActFound demonstrates accurate in-domain prediction and strong generalization across assay types and molecular scaffolds. We also demonstrate that ActFound can be used as an accurate alternative to the leading physics-based computational tool FEP+(OPLS4) by achieving comparable performance when using only a few data points for fine-tuning. Our promising results indicate that ActFound could be an effective bioactivity foundation model for compound bioactivity prediction, paving the way for machine-learning-based drug development and discovery. Traditional machine learning methods for drug development struggle with bioactivity prediction due to the limited number of compounds in each assay and assay incompatibilities. Feng et al. developed ActFound, a bioactivity foundation model trained by pairwise learning and meta-learning, that improves the accuracy and generalization of bioactivity prediction.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980824","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}

{"title":"On responsible machine learning datasets emphasizing fairness, privacy and regulatory norms with examples in biometrics and healthcare","authors":"Surbhi Mittal,&nbsp;Kartik Thakral,&nbsp;Richa Singh,&nbsp;Mayank Vatsa,&nbsp;Tamar Glaser,&nbsp;Cristian Canton Ferrer,&nbsp;Tal Hassner","doi":"10.1038/s42256-024-00874-y","DOIUrl":"10.1038/s42256-024-00874-y","url":null,"abstract":"Artificial Intelligence (AI) has seamlessly integrated into numerous scientific domains, catalysing unparalleled enhancements across a broad spectrum of tasks; however, its integrity and trustworthiness have emerged as notable concerns. The scientific community has focused on the development of trustworthy AI algorithms; however, machine learning and deep learning algorithms, popular in the AI community today, intrinsically rely on the quality of their training data. These algorithms are designed to detect patterns within the data, thereby learning the intended behavioural objectives. Any inadequacy in the data has the potential to translate directly into algorithms. In this study we discuss the importance of responsible machine learning datasets through the lens of fairness, privacy and regulatory compliance, and present a large audit of computer vision datasets. Despite the ubiquity of fairness and privacy challenges across diverse data domains, current regulatory frameworks primarily address human-centric data concerns. We therefore focus our discussion on biometric and healthcare datasets, although the principles we outline are broadly applicable across various domains. The audit is conducted through evaluation of the proposed responsible rubric. After surveying over 100 datasets, our detailed analysis of 60 distinct datasets highlights a universal susceptibility to fairness, privacy and regulatory compliance issues. This finding emphasizes the urgent need for revising dataset creation methodologies within the scientific community, especially in light of global advancements in data protection legislation. We assert that our study is critically relevant in the contemporary AI context, offering insights and recommendations that are both timely and essential for the ongoing evolution of AI technologies. There are pervasive concerns related to fairness, privacy and regulatory compliance in machine learning applications in healthcare, necessitating a reevaluation of dataset creation practices. Mittal et al. examine various computer vision datasets, providing insights to foster responsible AI development.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42256-024-00874-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974035","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}

{"title":"Data-driven discovery of movement-linked heterogeneity in neurodegenerative diseases","authors":"Mark Endo, Favour Nerrise, Qingyu Zhao, Edith V. Sullivan, Li Fei-Fei, Victor W. Henderson, Kilian M. Pohl, Kathleen L. Poston, Ehsan Adeli","doi":"10.1038/s42256-024-00882-y","DOIUrl":"https://doi.org/10.1038/s42256-024-00882-y","url":null,"abstract":"<p>Neurodegenerative diseases manifest different motor and cognitive signs and symptoms that are highly heterogeneous. Parsing these heterogeneities may lead to an improved understanding of underlying disease mechanisms; however, current methods are dependent on clinical assessments and an arbitrary choice of behavioural tests. Here we present a data-driven subtyping approach using video-captured human motion and brain functional connectivity from resting-state functional magnetic resonance imaging. We applied our framework to a cohort of individuals at different stages of Parkinson’s disease. The process mapped the data to low-dimensional measures by projecting them onto a canonical correlation space that identified three Parkinson’s disease subtypes: subtype I was characterized by motor difficulties and poor visuospatial abilities; subtype II exhibited difficulties in non-motor components of activities of daily living and motor complications (dyskinesias and motor fluctuations) and subtype III was characterized by predominant tremor symptoms. We conducted a convergent validity analysis by comparing our approach to existing and widely used approaches. The compared approaches yielded subtypes that were adequately well-clustered in the motion-brain representation space we created to delineate subtypes. Our data-driven approach, contrary to other forms of subtyping, derived biomarkers predictive of motion impairment and subtype memberships that were captured objectively by digital videos.</p>","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":23.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908969","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}

{"title":"Cognitive maps from predictive vision","authors":"Margaret C. von Ebers,&nbsp;Xue-Xin Wei","doi":"10.1038/s42256-024-00885-9","DOIUrl":"10.1038/s42256-024-00885-9","url":null,"abstract":"Constructing spatial maps from sensory inputs is challenging in both neuroscience and artificial intelligence. A recent study demonstrates that a self-attention neural network using predictive coding can generate an environmental map in its latent space as an agent that navigates the environment.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904419","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}

{"title":"Integrated structure prediction of protein–protein docking with experimental restraints using ColabDock","authors":"Shihao Feng,&nbsp;Zhenyu Chen,&nbsp;Chengwei Zhang,&nbsp;Yuhao Xie,&nbsp;Sergey Ovchinnikov,&nbsp;Yi Qin Gao,&nbsp;Sirui Liu","doi":"10.1038/s42256-024-00873-z","DOIUrl":"10.1038/s42256-024-00873-z","url":null,"abstract":"Protein complex structure prediction plays important roles in various applications, such as drug discovery and antibody design. However, due to limited prediction accuracy, there are frequent inconsistencies between the predictions and the experiments. Here we present ColabDock, a general framework adapting deep learning structure prediction models to integrate experimental restraints of different forms and sources without further large-scale retraining or fine tuning. With a generation–prediction architecture and trained ranking model, ColabDock outperforms HADDOCK and ClusPro using AlphaFold2 as the structure prediction model, not only in complex structure predictions with simulated residue and surface restraints but also in those assisted by nuclear magnetic resonance chemical shift perturbation as well as covalent labelling. It also assists antibody–antigen interface prediction with emulated interface scan restraints, which could be obtained by experiments such as deep mutational scanning. As a unified framework, we hope that ColabDock can help to bridge the gap between experimental and computational protein science. Despite rapid developments in predicting the complex structures of proteins, there are still inconsistencies between predictions and experiments. Feng et al. developed ColabDock, a general framework for deep learning models that integrates various experimental restraints and improves complex interface prediction, including antibody–antigen interactions.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895210","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}

{"title":"Author Correction: A 5′ UTR language model for decoding untranslated regions of mRNA and function predictions","authors":"Yanyi Chu,&nbsp;Dan Yu,&nbsp;Yupeng Li,&nbsp;Kaixuan Huang,&nbsp;Yue Shen,&nbsp;Le Cong,&nbsp;Jason Zhang,&nbsp;Mengdi Wang","doi":"10.1038/s42256-024-00890-y","DOIUrl":"10.1038/s42256-024-00890-y","url":null,"abstract":"","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42256-024-00890-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142091165","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}

{"title":"Deep learning prediction of glycopeptide tandem mass spectra powers glycoproteomics","authors":"Yu Zong,&nbsp;Yuxin Wang,&nbsp;Xipeng Qiu,&nbsp;Xuanjing Huang,&nbsp;Liang Qiao","doi":"10.1038/s42256-024-00875-x","DOIUrl":"10.1038/s42256-024-00875-x","url":null,"abstract":"Protein glycosylation, a post-translational modification of proteins by glycans, plays an important role in numerous physiological and pathological cellular functions. Glycoproteomics, the study of protein glycosylation on a proteome-wide scale, utilizes liquid chromatography coupled with tandem mass spectrometry (MS/MS) to get combinational information on glycosylation site, glycosylation level and glycan structure. However, current database searching methods for glycoproteomics often struggle with glycan structure determination due to the limited occurrence of structure-determining ions. Although spectral searching methods can leverage fragment intensity to facilitate the structure identification of glycopeptides, their application is hindered by difficulties in spectral library construction. In this work, we present DeepGP, a hybrid deep learning framework based on transformer and graph neural networks, for the prediction of MS/MS spectra and retention time of glycopeptides. Two graph neural network modules are employed to capture the branched glycan structure and predict glycan ion intensity, respectively. Additionally, a pretraining strategy is implemented to alleviate the insufficiency of glycoproteomics data. Testing on multiple biological datasets, DeepGP accurately predicts MS/MS spectra and retention time of glycopeptides, closely aligning with the experimental results. Comprehensive benchmarking of DeepGP on synthetic and biological datasets validates its effectiveness in distinguishing similar glycans. Based on various decoy methods, DeepGP in combination with database searching can increase glycopeptide detection sensitivity. We anticipate that DeepGP can inspire extensive future work in glycoproteomics. Glycosylation, a prevalent type of post-translational modification of proteins by glycan molecules, plays a major role in the proteome. Zong et al. present DeepGP, a hybrid deep learning framework based on transformer and graph neural network architectures that accurately predicts tandem mass spectra and retention times of glycopeptides, providing information on glycosylation and glycan structure.","PeriodicalId":48533,"journal":{"name":"Nature Machine Intelligence","volume":null,"pages":null},"PeriodicalIF":18.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794616","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}