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A prognostic model for overall survival of patients with early-stage non-small cell lung cancer: a multicentre, retrospective study

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The Lancet Digital Health 2020年第11期2卷 e594-e606页

作者： Lu, Cheng Bera, Kaustav Wang, Xiangxue Prasanna, Prateek Xu, Jun Janowczyk, Andrew Beig, Niha Yang, Michael Fu, Pingfu Lewis, James Choi, Humberto Schmid, Ralph A Berezowska, Sabina Schalper, Kurt Rimm, David Velcheti, Vamsidhar Madabhushi, Anant Department of Biomedical Engineering Case Western Reserve University Cleveland OH United States Department of Population and Quantitative Health Sciences Case Western Reserve University Cleveland OH United States Department of Biomedical Informatics Stony Brook University New York United States Jiangsu Key Laboratory of Big Data Analysis Technique Nanjing University of Information Science and Technology Nanjing China Precision Oncology Center Lausanne University Hospital Lausanne Switzerland University of Colorado Anschutz Medical Campus Aurora CO United States Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Nashville TN United States Department of Pulmonary Medicine Cleveland Clinic Cleveland OH United States Division of General Thoracic Surgery Inselspital University Hospital Bern Bern Switzerland The Institute of Pathology University of Bern Bern Switzerland Department of Pathology Yale University School of Medicine New Haven CT United States Perlmutter Cancer Center New York University NY United States Louis Stokes Cleveland Veterans Administration Medical Center Cleveland OH United States

Background: Intratumoural heterogeneity has been previously shown to be related to clonal evolution and genetic instability and associated with tumour progression. Phenotypically, it is reflected in the diversity of appearance and morphology within cell populations. Computer-extracted features relating to tumour cellular diversity on routine tissue images might correlate with outcome. This study investigated the prognostic ability of computer-extracted features of tumour cellular diversity (CellDiv) from haematoxylin and eosin (H&E)-stained histology images of non-small cell lung carcinomas (NSCLCs). Methods: In this multicentre, retrospective study, we included 1057 patients with early-stage NSCLC with corresponding diagnostic histology slides and overall survival information from four different centres. CellDiv features quantifying local cellular morphological diversity from H&E-stained histology images were extracted from the tumour epithelium region. A Cox proportional hazards model based on CellDiv was used to construct risk scores for lung adenocarcinoma (LUAD;270 patients) and lung squamous cell carcinoma (LUSC;216 patients) separately using data from two of the cohorts, and was validated in the two remaining independent cohorts (comprising 236 patients with LUAD and 335 patients with LUSC). We used multivariable Cox regression analysis to examine the predictive ability of CellDiv features for 5-year overall survival, controlling for the effects of clinical and pathological parameters. We did a gene set enrichment and Gene Ontology analysis on 405 patients to identify associations with differentially expressed biological pathways implicated in lung cancer pathogenesis. Findings: For prognosis of patients with early-stage LUSC, the CellDiv LUSC model included 11 discriminative CellDiv features, whereas for patients with early-stage LUAD, the model included 23 features. In the independent validation cohorts, patients predicted to be at a higher risk by the univ

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Beyond Low Earth Orbit: Biomonitoring, Artificial Intelligence, and Precision Space Health

arXiv

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arXiv 2021年

作者： Scott, Ryan T. Antonsen, Erik L. Sanders, Lauren M. Hastings, Jaden J.A. Park, Seung-Min Mackintosh, Graham Reynolds, Robert J. Hoarfrost, Adrienne L. Sawyer, Aenor Greene, Casey S. Glicksberg, Benjamin S. Theriot, Corey A. Berrios, Daniel C. Miller, Jack Babdor, Joel Barker, Richard Baranzini, Sergio E. Beheshti, Afshin Chalk, Stuart Delgado-Aparicio, Guillermo M. Haendel, Melissa Hamid, Arif A. Heller, Philip Jamieson, Daniel Jarvis, Katelyn J. Kalantari, John Khezeli, Kia Komarova, Svetlana V. Komorowski, Matthieu Kothiyal, Prachi Mahabal, Ashish Manor, Uri Martin, Hector Garcia Mason, Christopher E. Matar, Mona Mias, George I. Myers, Jerry G. Nelson, Charlotte Oribello, Jonathan Parsons-Wingerter, Patricia Prabhu, R.K. Qutub, Amina Ann Rask, Jon Saravia-Butler, Amanda Saria, Suchi Singh, Nitin Kumar Soboczenski, Frank Snyder, Michael Soman, Karthik van Valen, David Venkateswaran, Kasthuri Warren, Liz Worthey, Liz Yang, Jason H. Zitnik, Marinka Costes, Sylvain V. KBR Space Biosciences Division NASA Ames Research Center Moffett FieldCA94035 United States Department of Emergency Medicine Center for Space Medicine Baylor College of Medicine HoustonTX77030 United States Blue Marble Space Institute of Science Space Biosciences Division NASA Ames Research Center Moffett FieldCA94035 United States Department of Physiology and Biophysics Weill Cornell Medicine New YorkNY10065 United States Department of Urology Department of Radiology Stanford University School of Medicine StanfordCA94305 United States Bay Area Environmental Research Institute NASA Ames Research Center Moffett FieldCA94035 United States Mortality Research & Consulting Inc. HoustonTX77058 United States Space Biosciences Division NASA Ames Research Center Moffett FieldCA94035 United States UC Space Health Department of Orthopaedic Surgery University of California San Francisco San FranciscoCA94143 United States Center for Health AI Department of Biochemistry and Molecular Genetics University of Colorado School of Medicine Anschutz Medical Campus AuroraCO80045 United States Hasso Plattner Institute for Digital Health at Mount Sinai Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New YorkNY10065 United States Department of Preventive Medicine and Community Health UTMB GalvestonTX77551 United States Human Health and Performance Directorate NASA Johnson Space Center HoustonTX77058 United States Department of Microbiology and Immunology Department of Otolaryngology Head and Neck Surgery University of California San Francisco San FranciscoCA94143 United States The Gilroy AstroBiology Research Group The University of Wisconsin Madison MadisonWI53706 United States Weill Institute for Neurosciences Department of Neurology University of California San Francisco San FranciscoCA94158 United States Department of Chemistry University of North Florida JacksonvilleFL32224 United States Data Scienc

Human space exploration beyond low Earth orbit will involve missions of significant distance and duration. To effectively mitigate myriad space health hazards, paradigm shifts in data and space health systems are necessary to enable Earth-independence, rather than Earth-reliance. Promising developments in the fields of artificial intelligence and machine learning for biology and health can address these needs. We propose an appropriately autonomous and intelligent Precision Space Health system that will monitor, aggregate, and assess biomedical statuses;analyze and predict personalized adverse health outcomes;adapt and respond to newly accumulated data;and provide preventive, actionable, and timely insights to individual deep space crew members and iterative decision support to their crew medical officer. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration, on future applications of artificial intelligence in space biology and health. In the next decade, biomonitoring technology, biomarker science, spacecraft hardware, intelligent software, and streamlined data management must mature and be woven together into a Precision Space Health system to enable humanity to thrive in deep space. © 2021, CC BY.

关键词： Earth (planet)

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Beyond Low Earth Orbit: Biological Research, Artificial Intelligence, and Self-Driving Labs

arXiv

引用

arXiv 2021年

作者： Sanders, Lauren M. Yang, Jason H. Scott, Ryan T. Qutub, Amina Ann Martin, Hector Garcia Berrios, Daniel C. Hastings, Jaden J.A. Rask, Jon Mackintosh, Graham Hoarfrost, Adrienne L. Chalk, Stuart Kalantari, John Khezeli, Kia Antonsen, Erik L. Babdor, Joel Barker, Richard Baranzini, Sergio E. Beheshti, Afshin Delgado-Aparicio, Guillermo M. Glicksberg, Benjamin S. Greene, Casey S. Haendel, Melissa Hamid, Arif A. Heller, Philip Jamieson, Daniel Jarvis, Katelyn J. Komarova, Svetlana V. Komorowski, Matthieu Kothiyal, Prachi Mahabal, Ashish Manor, Uri Mason, Christopher E. Matar, Mona Mias, George I. Miller, Jack Myers, Jerry G. Nelson, Charlotte Oribello, Jonathan Park, Seung-Min Parsons-Wingerter, Patricia Prabhu, R.K. Reynolds, Robert J. Saravia-Butler, Amanda Saria, Suchi Sawyer, Aenor Singh, Nitin Kumar Soboczenski, Frank Snyder, Michael Soman, Karthik Theriot, Corey A. van Valen, David Venkateswaran, Kasthuri Warren, Liz Worthey, Liz Zitnik, Marinka Costes, Sylvain V. Blue Marble Space Institute of Science Space Biosciences Division NASA Ames Research Center Moffett Field CA94035 United States Center for Emerging and Re-Emerging Pathogens Department of Microbiology Biochemistry and Molecular Genetics Rutgers New Jersey Medical School NewarkNJ07103 United States KBR Space Biosciences Division NASA Ames Research Center Moffett Field CA94035 United States AI MATRIX Consortium Department of Biomedical Engineering University of Texas San Antonio and UT Health Sciences San AntonioTX78249 United States Biological Systems and Engineering Division Lawrence Berkeley National Lab. BerkeleyCA94608 United States DOE Agile BioFoundry EmeryvilleCA94608 United States Joint BioEnergy Institute EmeryvilleCA94608 United States Department of Physiology and Biophysics Weill Cornell Medicine New YorkNY10065 United States Office of the Center Director NASA Ames Research Center Moffett Field CA94035 United States Bay Area Environmental Research Institute NASA Ames Research Center Moffett Field CA94035 United States Space Biosciences Division NASA Ames Research Center Moffett Field CA94035 United States Department of Chemistry University of North Florida JacksonvilleFL32224 United States Center for Individualized Medicine Department of Surgery Department of Quantitative Health Sciences Mayo Clinic RochesterMN55905 United States Department of Emergency Medicine Center for Space Medicine Baylor College of Medicine HoustonTX77030 United States Department of Microbiology and Immunology Department of Otolaryngology Head and Neck Surgery University of California San Francisco San FranciscoCA94143 United States The Gilroy AstroBiology Research Group The University of Wisconsin - Madison MadisonWI53706 United States Weill Institute for Neurosciences Department of Neurology University of California San Francisco San FranciscoCA94158 United States Data Science Analytics Georgia Institute of Technology Lima15024

Space biology research aims to understand fundamental effects of spaceflight on organisms, develop foundational knowledge to support deep space exploration, and ultimately bioengineer spacecraft and habitats to stabilize the ecosystem of plants, crops, microbes, animals, and humans for sustained multi-planetary life. To advance these aims, the field leverages experiments, platforms, data, and model organisms from both spaceborne and ground-analog studies. As research is extended beyond low Earth orbit, experiments and platforms must be maximally autonomous, light, agile, and intelligent to expedite knowledge discovery. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration on artificial intelligence, machine learning, and modeling applications which offer key solutions toward these space biology challenges. In the next decade, the synthesis of artificial intelligence into the field of space biology will deepen the biological understanding of spaceflight effects, facilitate predictive modeling and analytics, support maximally autonomous and reproducible experiments, and efficiently manage spaceborne data and metadata, all with the goal to enable life to thrive in deep space. © 2021, CC BY.

关键词： Predictive analytics

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Publisher Correction: Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI

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Nature medicine 2022年第10期28卷 2218页

作者： Baptiste Vasey Myura Nagendran Bruce Campbell David A Clifton Gary S Collins Spiros Denaxas Alastair K Denniston Livia Faes Bart Geerts Mudathir Ibrahim Xiaoxuan Liu Bilal A Mateen Piyush Mathur Melissa D McCradden Lauren Morgan Johan Ordish Campbell Rogers Suchi Saria Daniel S W Ting Peter Watkinson Wim Weber Peter Wheatstone Peter McCulloch Nuffield Department of Surgical Sciences University of Oxford Oxford UK. baptiste.vasey@***. Institute of Biomedical Engineering Department of Engineering Science University of Oxford Oxford UK. baptiste.vasey@***. Critical Care Research Group Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK. baptiste.vasey@***. UKRI Centre for Doctoral Training in AI for Healthcare Imperial College London London UK. University of Exeter Medical School Exeter UK. Royal Devon and Exeter Hospital Exeter UK. Institute of Biomedical Engineering Department of Engineering Science University of Oxford Oxford UK. Centre for Statistics in Medicine Nuffield Department of Orthopaedics Rheumatology & Musculoskeletal Sciences University of Oxford Oxford UK. Institute of Health Informatics University College London London UK. British Heart Foundation Data Science Centre London UK. Health Data Research UK London UK. UCL Hospitals Biomedical Research Centre London UK. University Hospitals Birmingham NHS Foundation Trust Birmingham UK. Academic Unit of Ophthalmology Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham Birmingham UK. Moorfields Eye Hospital NHS Foundation Trust London UK. Healthplus.ai-R&D BV Amsterdam The Netherlands. Nuffield Department of Surgical Sciences University of Oxford Oxford UK. Department of Surgery Maimonides Medical Center Brooklyn NY USA. The Wellcome Trust London UK. The Alan Turing Institute London UK. Department of General Anesthesiology Anesthesiology Institute Cleveland Clinic Cleveland OH USA. The Hospital for Sick Children Toronto ON Canada. Dalla Lana School of Public Health University of Toronto Toronto ON Canada. Morgan Human Systems Ltd Shrewsbury UK. Medicines and Healthcare products Regulatory Agency London UK. HeartFlow Inc. Redwood City CA USA. Departments of Computer Science Statistics and Health Policy and Division of Informatics Johns Hopkins Un

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Erratum to 'Relation Between Mitral Valve Prolapse and Erectile Dysfunction (from a Nationwide Case-Control Study)': The American Journal of Cardiology 2019 Nov 15;124(10):1590-1593./ doi: 10.1016/***.2019.08.010

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The American journal of cardiology 2021年 142卷 161页

作者： Shiu-Dong Chung Ju-Chi Liu Tsai-Ning Lou Ben-Chang Shia Herng-Ching Lin Li-Ting Kao Division of Urology Department of Surgery Far Eastern Memorial Hospital Taipei Taiwan Department of Computer Science and Engineering and Graduate Program in Biomedical Informatics College of Informatics Yuan-Ze University Chung-Li Taiwan Sleep Research Center Taipei Medical University Hospital Taipei Taiwan. Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Division of Cardiovascular Medicine Department of Medicine Medical University Hospital-Shuang Ho Hospital TaipeiTaiwan. School of Health Care Administration Taipei Medical University Taipei Taiwan. Big Data Research Center Taipei Medical University Taipei Taiwan. Sleep Research Center Taipei Medical University Hospital Taipei Taiwan School of Health Care Administration Taipei Medical University Taipei Taiwan Graduate Institute of Life Sciences National Defense Medical Center Taipei Taiwan Department of Pharmacy Practice Tri-Service General Hospital Taipei Taiwan School of Pharmacy National Defense Medical Center Taipei Taiwan.. Electronic address: kaoliting@***.

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From FAIR to CURE: Guidelines for Computational Models of Biological Systems

arXiv

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arXiv 2025年

作者： Sauro, Herbert M. Agmon, Eran Blinov, Michael L. Gennari, John H. Hellerstein, Joe Heydarabadipour, Adel Hunter, Peter Jardine, Bartholomew E. May, Elebeoba Nickerson, David P. Smith, Lucian P. Bader, Gary D. Bergmann, Frank Boyle, Patrick M. Dräger, Andreas Faeder, James R. Feng, Song Freire, Juliana Fröhlich, Fabian Glazier, James A. Gorochowski, Thomas E. Helikar, Tomas Hoops, Stefan Imoukhuede, Princess Keating, Sarah M. Konig, Matthias Laubenbacher, Reinhard Loew, Leslie M. Lopez, Carlos F. Lytton, William W. McCulloch, Andrew Mendes, Pedro Myers, Chris J. Myers, Jerry G. Mulugeta, Lealem Niarakis, Anna van Niekerk, David D. Olivier, Brett G. Patrie, Alexander A. Quardokus, Ellen M. Radde, Nicole Rohwer, Johann M. Sahle, Sven Schaff, James C. Sego, T.J. Shin, Janis Snoep, Jacky L. Vadigepalli, Rajanikanth Wiley, H. Steve Waltemath, Dagmar Moraru, Ion Department of Bioengineering University of Washington SeattleWA98195-5061 United States Intelligent Systems Engineering and Biocomplexity Institute Indiana University Street BloomingtonIN47408 United States Center for Cardiovascular Biology University of Washington SeattleWA98195-5061 United States eScience Institute University of Washington SeattleWA98195-5061 United States Institute for Stem Cell and Regenerative Medicine University of Washington SeattleWA98195-5061 United States School of Biological Sciences University of Bristol 24 Tyndall Avenue BristolBS8 1TQ United Kingdom Departments of Physiology & Pharmacology Neurology Downstate Health Science University BrooklynNY11203 United States Department of Neurology Kings County Hospital BrooklynNY11203 United States NASA-John H. Glenn Research Center MS 110-3 21000 Brookpark Road ClevelandOH44135 United States Center for Cell Analysis and Modeling UConn Health 263 Farmington Avenue FarmingtonCT06030-6406 United States Amsterdam Institute for Life and Environment Vrije Universiteit Amsterdam De Boelelaan 1108 Amsterdam1081 HZ Netherlands Department of Pathology and Genomic Medicine Thomas Jefferson University 1020 Locust St PhiladelphiaPA19107 United States Biological Sciences Division Pacific Northwest National Laboratory 902 Battelle Blvd RichlandWA99354 United States Auckland Bioengineering Institute University of Auckland Auckland1010 New Zealand Center of Integrative Biology University of Toulouse III-Paul Sabatier 165 Rue Marianne Grunberg-Manago Toulouse31400 France Lifeware Group Inria Building Alan Turing 1 Rue Honoré d’Estienne d’Orves Palaiseau91120 France Multiscale Modeling Group Altos Labs Redwood CityCA94065 United States partner site Tübingen Tübingen Germany Ottfried-Müller-Str. 37 Tübingen72076 Germany 06120 Germany Department of Computer Science Center for Data Science New York University New YorkNY11201 United States Department of Bi

Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model credibility;the clarity of model descriptions and annotations for understandability;adherence to standards and open science practices for reproducibility;and the use of open standards and modular code for extensibility and reuse. We outline recommended and baseline requirements for each aspect of CURE, aiming to enhance the impact and trustworthiness of computational models, particularly in biomedical applications where credibility is paramount. Our perspective underscores the need for a more disciplined approach to modeling, aligning with emerging trends such as Digital Twins and emphasizing the importance of data and modeling standards for interoperability and reuse. Finally, we emphasize that given the non-trivial effort required to implement the guidelines, the community moves to automate as many of the guidelines as possible. © 2025, CC BY.

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

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Nature genetics 2023年第10期55卷 1778-1779页

作者： Nick Shrine Abril G Izquierdo Jing Chen Richard Packer Robert J Hall Anna L Guyatt Chiara Batini Rebecca J Thompson Chandan Pavuluri Vidhi Malik Brian D Hobbs Matthew Moll Wonji Kim Ruth Tal-Singer Per Bakke Katherine A Fawcett Catherine John Kayesha Coley Noemi Nicole Piga Alfred Pozarickij Kuang Lin Iona Y Millwood Zhengming Chen Liming Li Sara R A Wijnant Lies Lahousse Guy Brusselle Andre G Uitterlinden Ani Manichaikul Elizabeth C Oelsner Stephen S Rich R Graham Barr Shona M Kerr Veronique Vitart Michael R Brown Matthias Wielscher Medea Imboden Ayoung Jeong Traci M Bartz Sina A Gharib Claudia Flexeder Stefan Karrasch Christian Gieger Annette Peters Beate Stubbe Xiaowei Hu Victor E Ortega Deborah A Meyers Eugene R Bleecker Stacey B Gabriel Namrata Gupta Albert Vernon Smith Jian'an Luan Jing-Hua Zhao Ailin F Hansen Arnulf Langhammer Cristen Willer Laxmi Bhatta David Porteous Blair H Smith Archie Campbell Tamar Sofer Jiwon Lee Martha L Daviglus Bing Yu Elise Lim Hanfei Xu George T O'Connor Gaurav Thareja Omar M E Albagha Karsten Suhre Raquel Granell Tariq O Faquih Pieter S Hiemstra Annelies M Slats Benjamin H Mullin Jennie Hui Alan James John Beilby Karina Patasova Pirro Hysi Jukka T Koskela Annah B Wyss Jianping Jin Sinjini Sikdar Mikyeong Lee Sebastian May-Wilson Nicola Pirastu Katherine A Kentistou Peter K Joshi Paul R H J Timmers Alexander T Williams Robert C Free Xueyang Wang John L Morrison Frank D Gilliland Zhanghua Chen Carol A Wang Rachel E Foong Sarah E Harris Adele Taylor Paul Redmond James P Cook Anubha Mahajan Lars Lind Teemu Palviainen Terho Lehtimäki Olli T Raitakari Jaakko Kaprio Taina Rantanen Kirsi H Pietiläinen Simon R Cox Craig E Pennell Graham L Hall W James Gauderman Chris Brightling James F Wilson Tuula Vasankari Tarja Laitinen Veikko Salomaa Dennis O Mook-Kanamori Nicholas J Timpson Eleftheria Zeggini Josée Dupuis Caroline Hayward Ben Brumpton Claudia Langenberg Stefan Weiss Georg Homuth Carsten Oliver Schmidt Nicole Probst-Hensch Marjo-Riitta Jarvelin Alanna C Morrison Ozren Polasek Igor Department of Population Health Sciences University of Leicester Leicester UK. nick.shrine@leicester.ac.uk. Department of Population Health Sciences University of Leicester Leicester UK. Division of Respiratory Medicine and NIHR Nottingham Biomedical Research Centre University of Nottingham Nottingham UK. Leicester National Institute for Health and Care Research Biomedical Research Centre Glenfield Hospital Leicester UK. Channing Division of Network Medicine Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women's Hospital Boston MA USA. Harvard Medical School Boston MA USA. COPD Foundation Washington DC USA. Department of Clinical Science Unversity of Bergen Bergen Norway. Nuffield Department of Population Health University of Oxford Oxford UK. MRC Population Health Research Unit University of Oxford Oxford UK. Department of Epidemiology and Biostatistics School of Public Health Peking University Health Science Center Beijing China. Department of Respiratory Diseases Ghent Universital Hospital Ghent Belgium. Department of Bioanalysis Faculty of Pharmaceutical Sciences Ghent University Ghent Belgium. Department of Epidemiology Eramus Medical Center Rotterdam The Netherlands. Department of Internal Medicine Eramus Medical Center Rotterdam The Netherlands. Center for Public Health Genomics University of Virginia Charlottesville VA USA. Department of Medicine Columbia University Medical Center New York NY USA. Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK. Human Genetics Center Department of Epidemiology Human Genetics and Environmental Sciences School of Public Health The University of Texas Health Science Center at Houston Houston TX USA. MRC Centre for Environment and Health Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK. Department of Epidemiology and Public Health Swiss Tropical

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CSF1R + myeloid-monocytic cells drive CAR-T cell resistance in aggressive B cell lymphoma

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Cancer Cell 2025年

作者： David Stahl Philipp Gödel Hyatt Balke-Want Rahil Gholamipoorfard Paul Segbers Luis Tetenborg Mirjam Koker Janina Dörr Lisa Gregor Daniel Bachurski France Rose Adrian G. Simon Zinaida Good Josefine Jakob Björn Häupl Marieke Nill Ruth Flümann Tobias Riet Dinah Lange Stuart J. Blakemore Roland T. Ullrich Department I of Internal Medicine Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf University of Cologne Faculty of Medicine and University Hospital Cologne Cologne Germany Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany Else Kröner Forschungskolleg Clonal Evolution in Cancer University Hospital Cologne Cologne Germany Cancer Research Center Cologne Essen (CCCE) Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany Mildred Scheel School of Oncology Aachen Bonn Cologne Düsseldorf (MSSO ABCD) Faculty of Medicine and University Hospital of Cologne Cologne Germany Stanford Center for Cancer Cell Therapy Stanford Cancer Institute Stanford University Stanford CA USA Department of Translational Genomics Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany Division of Clinical Pharmacology Department of Medicine IV LMU University Hospital Member of the German Center for Lung Research (DZL) LMU Munich Munich Germany CECAD Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases University of Cologne Cologne Germany University of Cologne Institute for Biomedical Informatics Faculty of Medicine and University Hospital Cologne Cologne Germany Institute of Pathology University Hospital Cologne Faculty of Medicine University of Cologne Cologne Germany Department of Biomedical Data Science Stanford University School of Medicine Stanford CA USA Parker Institute for Cancer Immunotherapy Stanford University School of Medicine Stanford CA USA Department of Medicine Hematology and Oncology University Hospital Goethe University Frankfurt Frankfurt am Main Germany Frankfurt Cancer Institute (FCI) Frankfurt am Main Germany German Cancer Consortium (DKTK) partner site Frankfurt/Mainz a partnership between DKFZ and UCT Frankfurt-Marburg Germany Frankfurt am Main Germany German Cancer Research Center (DKFZ) Heidelberg Germany Max P

Despite the improvement, approximately 60% of patients with relapsed or refractory (r/r) aggressive B cell lymphoma (B-NHL) do not achieve durable benefit from CAR-T cell therapy. To elucidate factors associated with CAR-T therapy resistance, we conducted high-dimensional analyses of pre- and post-CAR-T cell specimens. In patients with non-durable response, we identified a prognostically relevant lymphoma-associated myeloid-monocytic (LAMM) gene signature. In-depth profiling revealed a distinct CSF1R + CD14 + CD68 + LAMM cell population in both human and murine B-NHL that inhibits CAR-T cell function and correlates with poor outcome. Cell-cell inference analysis uncovered that LAMM cells impair CAR-T cell function through a direct LAMM-T cell interaction via the PGE 2 -EP2/EP4 axis. In an autochthonous lymphoma mouse model, combined anti-CD19 CAR-T cell therapy with CSF1R blockade exhibited synergistic effects and improved survival. These findings provide strong rationale for combining anti-CD19 CAR-T cells with CSF1R inhibitors in treating r/r aggressive B-NHL patients.

关键词： CAR-T cell aggressive B-NHL CSF1R lymphoma tumor microenvironment myeloid cells

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Learning from learning machines: A new generation of AI technology to meet the needs of science

arXiv

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arXiv 2021年

作者： Pion-Tonachini, Luca Bouchard, Kristofer Martin, Hector Garcia Peisert, Sean Holtz, W. Bradley Aswani, Anil Dwivedi, Dipankar Wainwright, Haruko Pilania, Ghanshyam Nachman, Benjamin Marrone, Babetta L. Falco, Nicola Prabhat Arnold, Daniel Wolf-Yadlin, Alejandro Powers, Sarah Climer, Sharlee Jackson, Quinn Carlson, Ty Sohn, Michael Zwart, Petrus Kumar, Neeraj Justice, Amy Tomlin, Claire Jacobson, Daniel Micklem, Gos Gkoutos, Georgios V. Bickel, Peter J. Cazier, Jean-Baptiste Müller, Juliane Webb-Robertson, Bobbie-Jo Stevens, Rick Anderson, Mark Kreutz-Delgado, Ken Mahoney, Michael W. Brown, James B. Pattern Computer Inc. Friday HarborWA98250 United States Biosciences Area Lawrence Berkeley National Lab BerkeleyCA94803 United States Computational Research Division Lawrence Berkeley National Lab BerkeleyCA94720 United States Helen Wils Neuroscience Institute Redwood Center for Theoretical Neuroscience Uc Berkeley BerkeleyCA94720 United States Doe Agile BioFoundry Lawrence Berkeley National Laboratory BerkeleyCA94803 United States Joint BioEnergy Institute Lawrence Berkeley National Laboratory BerkeleyCA94803 United States Bcam Basque Center for Applied Mathematics Bilbao48009 Spain Computer Science University of California Davis DavisCA95616 United States Cenic La MiradaCA90638 United States Health Informatics University of California Davis School of Medicine SacramentoCA95817 United States Berkeley Institute for Data Science University of California Berkeley BerkeleyCA94720 United States Industrial Engineering and Operations Research University of California Berkeley BerkeleyCA94720 United States Environmental & Earth Sciences Area Lawrence Berkeley National Laboratory BerkeleyCA94803 United States Nuclear Engineering University of California Berkeley BerkeleyCA94720 United States Materials Science and Technology Division Los Alamos National Laboratory Los AlamosNM87545 United States Physics Division Lawrence Berkeley National Lab BerkeleyCA94720 United States Bioscience Division Los Alamos National Laboratory Los AlamosNM87545 United States Earth and Environmental Sciences Area Lawrence Berkeley National Lab BerkeleyCA94803 United States Energy Technologies Area Lawrence Berkeley National Lab BerkeleyCA94803 United States Computing and Computational Sciences Oak Ridge National Laboratory Oak RidgeTN37831 United States Industrial & Systems Engineering The University of Tennessee KnoxvilleTN37996 United States Department of Computer Science University of Missouri-Saint Louis St. LouisMO63121 United

We outline emerging opportunities and challenges to enhance the utility of AI for scientific discovery. The distinct goals of AI for industry versus the goals of AI for science create tension between identifying patterns in data versus discovering patterns in the world from data. If we address the fundamental challenges associated with "bridging the gap" between domain-driven scientific models and data-driven AI learning machines, then we expect that these AI models can transform hypothesis generation, scientific discovery, and the scientific process itself. © 2021, CC BY.

关键词： Learning systems

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