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CellLENS enables cross-domain information fusion for enhanced cell population delineation in single-cell spatial omics data

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Nature immunology 2025年 2025 May 22页

作者： Bokai Zhu Sheng Gao Shuxiao Chen Yuchen Wang Jason Yeung Yunhao Bai Amy Y Huang Yao Yu Yeo Guanrui Liao Shulin Mao Zhenghui G Jiang Scott J Rodig Ka-Chun Wong Alex K Shalek Garry P Nolan Sizun Jiang Zongming Ma Ragon Institute of MGH MIT and Harvard Cambridge MA USA. Broad Institute of MIT and Harvard Cambridge MA USA. Massachusetts Institute of Technology Cambridge MA USA. Department of Statistics and Data Science The Wharton School University of Pennsylvania Philadelphia PA USA. Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA. Department of Computer Science City University of Hong Kong Hong Kong People's Republic of China. Dana-Farber Cancer Institute Boston MA USA. Center of Hepato-Pancreato-Biliary Surgery The First Affiliated Hospital of Sun Yat-sen University Guangzhou People's Republic of China. Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston MA USA. Program in Biological and Biomedical Sciences Harvard Medical School Boston MA USA. Division of Gastroenterology/Liver Center Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA. Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA USA. Institute for Medical Engineering and Science Massachusetts Institute of Technology Cambridge MA USA. Department of Chemistry Massachusetts Institute of Technology Cambridge MA USA. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge MA USA. Department of Pathology Stanford University Stanford CA USA. gnolan@stanford.edu. Broad Institute of MIT and Harvard Cambridge MA USA. sjiang3@bidmc.harvard.edu. Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA. sjiang3@bidmc.harvard.edu. Dana-Farber Cancer Institute Boston MA USA. sjiang3@bidmc.harvard.edu. Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA USA. sjiang3@bidmc.harvard.edu. Department of Statistics and Data Science Yale University New Haven CT USA. zongming.ma@yale.edu.

Delineating cell populations is crucial for understanding immune function in health and disease. Spatial omics technologies offer insights by capturing three complementary domains: single-cell molecular biomarker expression, cellular spatial relationships and tissue architecture. However, current computational methods often fail to fully integrate these multidimensional data, particularly for immune cell populations and intrinsic functional states. We introduce Cell Local Environment and Neighborhood Scan (CellLENS), a self-supervised computational method that learns cellular representations by fusing information across three spatial omics domains (expression, neighborhood and image). CellLENS markedly enhances de novo discovery of biologically relevant immune cell populations at fine granularity by integrating individual cells' molecular profiles with their neighborhood context and tissue localization. By applying CellLENS to diverse spatial proteomic and transcriptomic datasets across multiple tissue types and disease settings, we uncover unique immune cell populations functionally stratified according to their spatial contexts. Our work demonstrates the power of multi-domain data integration in spatial omics to reveal insights into immune cell heterogeneity and tissue-specific functions.

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LANDMARK ALTERNATING DIFFUSION

arXiv

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arXiv 2024年

作者： Yeh, Sing-Yuan Wu, Hau-Tieng Talmon, Ronen Tsui, Mao-Pei Data Science Degree Program National Taiwan University Academia Sinica Taipei106 Taiwan Courant Institute of Mathematical Sciences New York University New YorkNY10012 United States Viterbi Faculty of Electrical and Computer Engineering Technion - Israel Institute of Technology Haifa3200003 Israel Department of Mathematics National Taiwan University Taipei106 Taiwan National Center for Theoretical Sciences Mathematics Division Taipei106 Taiwan

Alternating Diffusion (AD) is a commonly applied diffusion-based sensor fusion algorithm. While it has been successfully applied to various problems, its computational burden remains a limitation. Inspired by the landmark diffusion idea considered in the Robust and Scalable Embedding via Landmark Diffusion (ROSELAND), we propose a variation of AD, called Landmark AD (LAD), which captures the essence of AD while offering superior computational efficiency. We provide a series of theoretical analyses of LAD under the manifold setup and apply it to the automatic sleep stage annotation problem with two electroencephalogram channels to demonstrate its *** Codes 53Z50, 65D18 © 2024, CC BY.

关键词： Diffusion

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Empowering Biomedical Discovery with AI Agents

arXiv

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arXiv 2024年

作者： Gao, Shanghua Fang, Ada Huang, Yepeng Giunchiglia, Valentina Noori, Ayush Schwarz, Jonathan Richard Ektefaie, Yasha Kondic, Jovana Zitnik, Marinka Department of Biomedical Informatics Harvard Medical School BostonMA United States Department of Chemistry and Chemical Biology Harvard University CambridgeMA United States Program in Biological and Biomedical Sciences Harvard Medical School BostonMA United States Department of Brain Sciences Imperial College London London United Kingdom Harvard College CambridgeMA United States Program in Biomedical Informatics Harvard Medical School BostonMA United States Department of Electrical Engineering and Computer Science MIT CambridgeMA United States Kempner Institute for the Study of Natural and Artificial Intelligence Harvard University MA United States Broad Institute of MIT and Harvard CambridgeMA United States Harvard Data Science Initiative CambridgeMA United States

We envision "AI scientists" as systems capable of skeptical learning and reasoning that empower biomedical research through collaborative agents that integrate AI models and biomedical tools with experimental platforms. Rather than taking humans out of the discovery process, biomedical AI agents combine human creativity and expertise with AI’s ability to analyze large datasets, navigate hypothesis spaces, and execute repetitive tasks. AI agents are poised to be proficient in various tasks, planning discovery workflows and performing self-assessment to identify and mitigate gaps in their knowledge. These agents use large language models and generative models to feature structured memory for continual learning and use machine learning tools to incorporate scientific knowledge, biological principles, and theories. AI agents can impact areas ranging from virtual cell simulation, programmable control of phenotypes, and the design of cellular circuits to developing new therapies. © 2024, CC BY.

关键词： Adversarial machine learning

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Artificial Intelligence for Digital and Computational Pathology

arXiv

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arXiv 2023年

作者： Song, Andrew H. Jaume, Guillaume Williamson, Drew F.K. Lu, Ming Y. Vaidya, Anurag Miller, Tiffany R. Mahmood, Faisal Department of Pathology Brigham and Women's Hospital Harvard Medical School BostonMA United States Department of Pathology Massachusetts General Hospital Harvard Medical School BostonMA United States Cancer Program Broad Institute of Harvard and MIT CambridgeMA United States Data Science Program Dana-Farber Cancer Institute BostonMA United States Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology CambridgeMA United States Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology CambridgeMA United States Harvard Medical School BostonMA United States

Advances in digitizing tissue slides and the fast-paced progress in artificial intelligence, including deep learning, have boosted the field of computational pathology. This field holds tremendous potential to automate clinical diagnosis, predict patient prognosis and response to therapy, and discover new morphological biomarkers from tissue images. Some of these artificial intelligence-based systems are now getting approved to assist clinical diagnosis;however, technical barriers remain for their widespread clinical adoption and integration as a research tool. This Review consolidates recent methodological advances in computational pathology for predicting clinical end points in whole-slide images and highlights how these developments enable the automation of clinical practice and the discovery of new biomarkers. We then provide future perspectives as the field expands into a broader range of clinical and research tasks with increasingly diverse modalities of clinical data. © 2023, CC BY.

关键词： Pathology

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25th Annual Computational Neuroscience Meeting CNS-2016, Seogwipo City, South Korea, July 2-7, 2016 Abstracts

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BMC NEUROscience 2016年第1期17卷 1-112页

作者： [Anonymous] Computational Neurobiology Laboratory The Salk Institute for Biological Studies San Diego USA UNIC CNRS Gif sur Yvette France The European Institute for Theoretical Neuroscience (EITN) Paris France ATR Computational Neuroscience Laboratories Kyoto Japan Krembil Research Institute University Health Network Toronto Canada Department of Physiology University of Toronto Toronto Canada Department of Medicine (Neurology) University of Toronto Toronto Canada Department of Physics University of New Hampshire Durham USA Department of Neurophysiology Nencki Institute of Experimental Biology Warsaw Poland Department of Theory Wigner Research Centre for Physics of the Hungarian Academy of Sciences Budapest Hungary Department of Mathematical Sciences KAIST Daejoen Republic of Korea Department of Mathematics University of Houston Houston USA Department of Biochemistry & Cell Biology and Institute of Biosciences and Bioengineering Rice University Houston USA Department of Biology and Biochemistry University of Houston Houston USA Grupo de Neurocomputación Biológica Dpto. de Ingeniería Informática Escuela Politécnica Superior Universidad Autónoma de Madrid Madrid Spain Department of Biological Sciences University of Southern California Los Angeles USA Center for Neuroscience Korea Institute of Science and Technology Seoul South Korea Department of Neurology Albert Einstein College of Medicine Bronx USA Center for Neuroscience KIST Seoul South Korea Department of Neuroscience University of Science and Technology Daejon South Korea Systems Neuroscience Group QIMR Berghofer Medical Research Institute Herston Australia Department of Psychology Yonsei University Seoul South Korea Department of Psychiatry Kyung Hee University Hospital at Gangdong Seoul South Korea Department of Psychiatry Veterans Administration Boston Healthcare System and Harvard Medical School Brockton USA Department of Electrical and Electronic Engineering The University of Melbourne Parkvil

A1 Functional advantages of cell-type heterogeneity in neural circuits Tatyana O. Sharpee A2 Mesoscopic modeling of propagating waves in visual cortex Alain Destexhe A3 Dynamics and biomarkers of mental disorders Mitsuo Kawato F1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneurons Vladislav Sekulić, Frances K. Skinner F2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brains Daniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán Somogyvári F3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks. Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir Josić O1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generators Irene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo Varona O2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrain Eunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun Choi O3 Modeling auditory stream segregation, build-up and bistability James Rankin, Pamela Osborn Popp, John Rinzel O4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fields Alejandro Tabas, André Rupp, Emili Balaguer-Ballester O5 A simple model of retinal response to multi-electrode stimulation Matias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish Meffin O6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination task Veronika Koren, Timm Lochmann, Valentin Dragoi, Klaus Obermayer O7 Input-location dependent gain modulation in cerebellar nucleus neurons Maria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Ni

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Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017 (vol 395, pg 1779, 2020)

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LANCET 2020年第10239期395卷 1762-1762页

作者： Reiner, R. C., Jr. Hay, S., I Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Global Health School of Medicine University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States College of Health and Medical Sciences Haramaya University Harar Ethiopia Department of Epidemiology and Biostatistics Haramaya University Harar Ethiopia Department of Medical Laboratory Sciences Haramaya University Harar Ethiopia School of Nursing and Midwifery Haramaya University Harar Ethiopia School of Pharmacy Haramaya University Harar Ethiopia School of Public Health Haramaya University Harar Ethiopia Haramaya University Harar Ethiopia Advanced Diagnostic and Interventional Radiology Research Center Tehran University of Medical Sciences Tehran Iran Cancer Biology Research Center Tehran University of Medical Sciences Tehran Iran Cancer Research Institute Tehran University of Medical Sciences Tehran Iran Department of Economics and Management Sciences for Health Tehran University of Medical Sciences Tehran Iran Department of Environmental Health Engineering Tehran University of Medical Sciences Tehran Iran Department of Epidemiology and Biostatistics Tehran University of Medical Sciences Tehran Iran Department of Health Management and Economics Tehran University of Medical Sciences Tehran Iran Department of Microbiology Tehran University of Medical Sciences Tehran Iran Department of Pharmacology Tehran University of Medical Sciences Tehran Iran Digestive Diseases Research Institute Tehran University of Medical Sciences Tehran Iran Endocrinology and Metabolism Research Center Tehran University of Medical Sciences Tehran Iran Hematology-Oncology and Stem Cell Transplantation Research Center Tehran University of Medical Sciences Tehran Iran Iran National Institute of Health Research Tehran University of Medical Sciences Tehran Iran Metabolomics and

Summary Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood *** We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor *** The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy *** By co-analysing geospatial trends in d

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The power of specialty palliative care: moving towards a systems perspective

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The Lancet Haematology 2021年第5期8卷 e376-e381页

作者： Barnato, Amber E Khayal, Inas S The Dartmouth Institute for Health Policy and Clinical Practice Geisel School of Medicine at Dartmouth Lebanon NH United States Department of Biomedical Data Science Geisel School of Medicine at Dartmouth Lebanon NH United States Section of Palliative Care Department of Medicine Dartmouth-Hitchcock Medical Center Lebanon NH United States Department of Computer Science Dartmouth College Hanover NH United States Cancer Population Sciences Program Norris Cotton Cancer Center Lebanon NH United States

Three palliative care clinical trials were presented at the 2020 American Society for Clinical Oncology Annual Meeting. The heterogeneity in populations, models of care, study design, and assessment of clinical outcomes across these three studies show the broad opportunities for research into interventions for palliative care. In this Viewpoint, we summarise the characteristics of these studies, discuss their novel features and lingering questions, and offer a suggestion for further expanding the focus of clinical trials for delivery of palliative care in the future. We particularly argue that the propensity to characterise palliative care as if it was a clinical or biomedical intervention hampers the design and evaluation of complex clinical interventions that influence clinicians, systems for health-care delivery, individual patients, and their families. © 2021 Elsevier Ltd

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Curriculum Guidelines for Undergraduate programs in data science

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Statistics and Its Application 1000年第1期4卷 15-30页

作者： Richard D. De Veaux Mahesh Agarwal Maia Averett Benjamin S. Baumer Andrew Bray Thomas C. Bressoud Lance Bryant Lei Z. Cheng Amanda Francis Robert Gould Albert Y. Kim Matt Kretchmar Qin Lu Ann Moskol Deborah Nolan Roberto Pelayo Sean Raleigh Ricky J. Sethi Mutiara Sondjaja Neelesh Tiruviluamala Paul X. Uhlig Talitha M. Washington Curtis L. Wesley David White Ping Ye 1Department of Mathematics and Statistics Williams College Williamstown Massachusetts 01267 2Department of Mathematics and Statistics University of Michigan Dearborn Michigan 48128-2406 3Department of Mathematics and Computer Science Mills College Oakland California 94613 4Department of Statistical & Data Sciences Smith College Northampton Massachusetts 01063 5Department of Mathematics Reed College Portland Oregon 97202 6Department of Mathematics and Computer Science Denison University Granville Ohio 43023 7Department of Mathematics Shippensburg University Shippensburg Pennsylvania 17257 8Department of Mathematics Olivet Nazarene University Bourbonnais Illinois 60914 9Department of Mathematics Brigham Young University Provo Utah 84601 10Department of Statistics University of California Los Angeles Los Angeles California 90095-1554 11Department of Mathematics Middlebury College Middlebury Vermont 05753 12Department of Mathematics and Computer Science Denison University Granville Ohio 43023 13Department of Mathematics Lafayette College Easton Pennsylvania 18042-1780 14Department of Mathematics and Computer Science Rhode Island College Providence Rhode Island 02908 15Department of Statistics University of California Berkeley California 94720 16Department of Mathematics University of Hawaii Hilo Hawaii 96720-4091 17Department of Mathematics Westminster College Salt Lake City Utah 84105 18Department of Computer Science Fitchburg State University Fitchburg Massachusetts 01420 19Department of Mathematics New York University New York New York 10012 20Department of Mathematics University of Southern California Los Angeles California 90089 21Department of Mathematics St. Mary's University San Antonio Texas 78228 22Department of Mathematics Howard University Washington DC 20059 23Department of Mathematics LeTourneau University Longview Texas 75602 24Department of Mathematics and Computer Science Denison University Granville Ohio 43023 25Department of M

The Park City Math Institute 2016 Summer Undergraduate Faculty program met for the purpose of composing guidelines for undergraduate programs in data science. The group consisted of 25 undergraduate faculty from a variety of institutions in the United States, primarily from the disciplines of mathematics, statistics, and computer science. These guidelines are meant to provide some structure for institutions planning for or revising a major in data science.

关键词： curriculum statistics education computer science education

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Scientific discovery in the age of artificial intelligence

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NATURE 2023年第7978期621卷 E33-E33页

作者： Wang, Hanchen Fu, Tianfan Du, Yuanqi Gao, Wenhao Huang, Kexin Liu, Ziming Chandak, Payal Liu, Shengchao Van Katwyk, Peter Deac, Andreea Anandkumar, Anima Bergen, Karianne Gomes, Carla P. Ho, Shirley Kohli, Pushmeet Lasenby, Joan Leskovec, Jure Liu, Tie-Yan Manrai, Arjun Marks, Debora Ramsundar, Bharath Song, Le Sun, Jimeng Tang, Jian Velickovic, Petar Welling, Max Zhang, Linfeng Coley, Connor W. Bengio, Yoshua Zitnik, Marinka Department of Engineering University of Cambridge Cambridge UK Department of Computing and Mathematical Sciences California Institute of Technology Pasadena CA USA NVIDIA Santa Clara CA USA Department of Computational Science and Engineering Georgia Institute of Technology Atlanta GA USA Department of Computer Science Cornell University Ithaca NY USA Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA USA Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge MA USA Department of Computer Science Stanford University Stanford CA USA Department of Physics Massachusetts Institute of Technology Cambridge MA USA Harvard-MIT Program in Health Sciences and Technology Cambridge MA USA Mila – Quebec AI Institute Montreal Quebec Canada Université de Montréal Montreal Quebec Canada HEC Montréal Montreal Quebec Canada CIFAR AI Chair Toronto Ontario Canada Department of Earth Environmental and Planetary Sciences Brown University Providence RI USA Data Science Institute Brown University Providence RI USA Center for Computational Astrophysics Flatiron Institute New York NY USA Department of Astrophysical Sciences Princeton University Princeton NJ USA Department of Physics Carnegie Mellon University Pittsburgh PA USA Department of Physics and Center for Data Science New York University New York NY USA Google DeepMind London UK Department of Computer Science and Technology University of Cambridge Cambridge UK Microsoft Research Beijing China Department of Biomedical Informatics Harvard Medical School Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Harvard Data Science Initiative Cambridge MA USA Kempner Institute for the Study of Natural and Artificial Intelligence Harvard University Cambridge MA USA Department of Systems Biology Harvard Medical School Boston MA USA Deep Forest Sciences Palo Alto CA USA BioMap Beijing China Mo

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Precision Rehabilitation for Patients Post-Stroke based on Electronic Health Records and Machine Learning

arXiv

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arXiv 2024年

作者： Gao, Fengyi Zhang, Xingyu Sivarajkumar, Sonish Denny, Parker E. Aldhahwani, Bayan M. Visweswaran, Shyam Shi, Ryan Hogan, William Bove, Allyn Wang, Yanshan Department of Health Information Management University of Pittsburgh PittsburghPA United States Department of Communication Science and Disorders University of Pittsburgh PittsburghPA United States Intelligent Systems Program School of Computing and Information University of Pittsburgh PittsburghPA United States Department of Physical Therapy University of Pittsburgh PittsburghPA United States Department of Medical Rehabilitation Sciences Umm Al-Qura University Makkah Saudi Arabia Department of Biomedical Informatics University of Pittsburgh PittsburghPA United States Department of Computer Science University of Pittsburgh Medical Center PittsburghPA United States Data Science Institute Medical College of Wisconsin MilwaukeeWI United States Hillman Cancer Center University of Pittsburgh Medical Center PittsburghPA United States

Objective In this study, we utilized statistical analysis and machine learning methods to examine whether rehabilitation exercises can improve patients post-stroke functional abilities, as well as forecast the improvement in functional abilities. Our dataset is patients’ rehabilitation exercises and demographic information recorded in the unstructured electronic health records (EHRs) data and free-text rehabilitation procedure notes. Through this study, our ultimate goal is to pinpoint the specific rehabilitation exercises that can effectively aid post-stroke patients in improving their functional outcomes in basic mobility (BM) and applied cognitive (AC) domains. data sources We collected data for 265 stroke patients from the University of Pittsburgh Medical Center, accessed through the Rehabilitation datamart With Informatics iNfrastructure for Research (ReDWINE). Methods We employed a pre-existing natural language processing (NLP) algorithm to extract data on rehabilitation exercises and developed a rule-based NLP algorithm to extract Activity Measure for Post-Acute Care (AM-PAC) scores, covering basic mobility (BM) and applied cognitive (AC) domains, from procedure notes. AM-PAC scores were collected at the initial rehabilitation visit and followed up at one and two months—key recovery periods. Changes in AM-PAC scores were classified based on the minimal clinically important difference (MCID), and significance was assessed using Friedman and Wilcoxon tests. To identify impactful exercises, we used Chi-square tests, Fisher's exact tests, and logistic regression for odds ratios. Additionally, we developed five machine learning models—logistic regression (LR), Adaboost (ADB), support vector machine (SVM), gradient boosting (GB), and random forest (RF)—to predict outcomes in functional ability. Results statistical analyses revealed significant associations between functional improvements and specific exercises. In the AC domain, the BALANCE exercise showed substant

关键词： statistical tests

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