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39th IEEE International Conference on data Engineering, ICDE 2023

作者： Peng, Bo Ren, Zhiyun Parthasarathy, Srinivasan Ning, Xia The Ohio State University Department of Computer Science and Engineering United States The Ohio State University Department of Biomedical Informatics United States The Ohio State University Translational Data Analytics Institute Department of Computer Science and Engineering United States The Ohio State University Translational Data Analytics Institute Department of Biomedical Informatics Department of Computer Science and Engineering United States

ISBN: (纸本)9798350322279

Sequential recommendation aims to identify and recommend the next few items of users' interest. It becomes an effective tool to help users select their favorite items from a variety of options. A key challenge in sequential recommendation is to learn the patterns and dynamics, which are most pertinent to inform future interactions of users. With the prosperity of deep learning, many deep models, particularly based on recurrent neural networks [1] and with attention mechanisms [2] , [3] , have been developed for sequential recommendation purposes. However, our analysis demonstrates that, these deep models, particularly those with attention mechanisms, may not always learn meaningful attention weights from the extremely sparse recommendation data, and thus, could degrade the recommendation performance. Therefore, in this study, instead of deep models, we develop novel, effective and efficient hybrid associations models (HAM) to better learn from the sparse and limited recommendation data. This study has been published in IEEE Transactions on Knowledge and data Engineering. Please refer to the full manuscript [4] for more details. © 2023 IEEE.

关键词： Recurrent neural networks

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CanSeer: a translational methodology for developing personalized cancer models and therapeutics

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Scientific Reports 2025年第1期15卷 1-22页

作者： Butt, Rida Nasir Amina, Bibi Sultan, Muhammad Umer Tanveer, Zain Bin Gondal, Mahnoor Naseer Hussain, Risham Khan, Salaar Akbar, Rida Nasir, Zainab Khalid, Muhammad Farhan Channan-Khan, Asher Alban Faisal, Amir Shoaib, Muhammad Chaudhary, Safee Ullah Biomedical Informatics and Engineering Research Laboratory (BIRL) Syed Babar Ali School of Science and Engineering Department of Life Sciences Lahore University of Management Sciences Lahore 54792 Pakistan Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor 48109 MI United States Michigan Center for Translational Pathology University of Michigan Ann Arbor 48109 MI United States Data Science Institute Lancaster University Lancaster LA1 4YW United Kingdom Center for Eukaryotic Gene Regulation Department of Biochemistry and Molecular Biology Penn State University University Park 16802 PA United States Mayo Clinic School of Medicine New York University NY United States Cancer Therapeutics Lab Syed Babar Ali School of Science and Engineering Department of Life Sciences Lahore University of Management Sciences Lahore 54792 Pakistan Epigenome and Genome Integrity Lab (EaGIL) Syed Babar Ali School of Science and Engineering Department of Life Sciences Lahore University of Management Sciences Lahore 54792 Pakistan

Computational modeling and analysis of biomolecular network models annotated with omics data are emerging as a versatile tool for designing personalized therapies. Current endeavors aimed at employing in silico models towards personalized cancer therapeutics remain limited in providing all-in-one approach that ascertains actionable targets, re-positions FDA (Food and Drug Administration) approved drugs, furnishes quantitative cues on therapy responses such as efficacy and cytotoxic effect, and identifies novel drug combinations. Here we propose “CanSeer”—a methodology for developing personalized therapeutics. CanSeer employs patient-specific genetic alterations and RNA-seq data to annotate in silico models followed by dynamical network analyses towards assessment of treatment responses. To exemplify, three use cases involving paired samples, unpaired samples, and cancer samples only, of lung squamous cell carcinoma (LUSC) patients are provided. CanSeer reveals the effectiveness of repositioned drugs along with the identification of several novel LUSC treatment combinations including Afuresertib + Palbociclib, Dinaciclib + Trametinib, Afatinib + Oxaliplatin, Ulixertinib + Olaparib, etc. © The Author(s) 2025.

关键词： Biomolecular network modeling Dynamical analysis of in silico models Integrative omics Personalized mono- and combinatorial therapies Therapeutic screening translational cancer systems biology

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Control Theory to Design and Evaluate Audit and Feedback Interventions

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Studies in Health Technology and informatics 2019年 263卷 159-170页

作者： Gude, Wouter T. Peek, Niels Department of Medical Informatics Amsterdam UMC University of Amsterdam Amsterdam Public Health Research Institute Netherlands Division of Informatics Imaging and Data Science School of Health Sciences University of Manchester United Kingdom NIHR Greater Manchester Patient Safety Translational Research Centre University of Manchester United Kingdom

ISBN: (纸本)9781614999904

Control theory is about the processes underlying the behaviour of self-regulating agents. It proposes that behaviour is regulated by a negative feedback loop, in which the agent compares the perception of its current state against a goal state and will strive to reduce perceived discrepancies by modifying its behaviour. Although studies in health informatics often do not report the use of this theory, the principle of a negative feedback loop underlies many applications in the field. This chapter describes how control theory fits within health informatics, discussing its role in the development and assessment of audit and feedback interventions in healthcare. Control theory has been used to synthesise evidence of audit and feedback, and to design and evaluate interventions to improve the quality of blood transfusion practice, cardiac rehabilitation, and intensive care. This has driven progress in our understanding of the underlying mechanisms of audit and feedback for improving health care, and has helped to design better interventions. © 2019 The authors and IOS Press.

关键词： Feedback

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ENIGMA-Meditation: Worldwide Consortium for Neuroscientific Investigations of Meditation Practices

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Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2025年第4期10卷 425-436页

作者： Ganesan, Saampras Barrios, Fernando A. Batta, Ishaan Bauer, Clemens C.C. Braver, Todd S. Brewer, Judson A. Brown, Kirk Warren Cahn, Rael Cain, Joshua A. Calhoun, Vince D. Cao, Lei Chetelat, Gaël Ching, Christopher R.K. Creswell, J. David Dagnino, Paulina Clara Davanger, Svend Davidson, Richard J. Deco, Gustavo Dutcher, Janine M. Escrichs, Anira Eyler, Lisa T. Fani, Negar Farb, Norman A.S. Fialoke, Suruchi Fresco, David M. Garg, Rahul Garland, Eric L. Goldin, Philippe Hafeman, Danella M. Jahanshad, Neda Kang, Yoona Khalsa, Sahib S. Kirlic, Namik Lazar, Sara W. Lutz, Antoine McDermott, Timothy J. Pagnoni, Giuseppe Piguet, Camille Prakash, Ruchika S. Rahrig, Hadley Reggente, Nicco Saccaro, Luigi F. Sacchet, Matthew D. Siegle, Greg J. Tang, Yi-Yuan Thomopoulos, Sophia I. Thompson, Paul M. Torske, Alyssa Treves, Isaac N. Tripathi, Vaibhav Tsuchiyagaito, Aki Turner, Matthew D. Vago, David R. Valk, Sofie Zeidan, Fadel Zalesky, Andrew Turner, Jessica A. King, Anthony P. Department of Biomedical Engineering The University of Melbourne Carlton VIC Australia Contemplative Studies Centre Melbourne School of Psychological Sciences The University of Melbourne Melbourne VIC Australia Systems Lab of Neuroscience Neuropsychiatry and Neuroengineering The University of Melbourne Parkville VIC Australia Universidad Nacional Autónoma de México Instituto de Neurobiolgía México Querétaro Mexico Center for Translational Research in Neuroimaging and Data Science: Georgia State University Georgia Institute of Technology and Emory University Atlanta GA United States Department of Psychology Northeastern University Boston Massachusetts Brain and Cognitive Science McGovern Institute for Brain Research Massachusetts Institute of Technology Cambridge Massachusetts Department of Psychological and Brain Sciences Washington University St. Louis Missouri Department of Behavioral and Social Sciences Brown University School of Public Health Providence Rhode Island Department of Psychology Carnegie Mellon University Pittsburgh PA United States University of Southern California Department of Psychiatry & Behavioral Sciences Los Angeles California University of Southern California Center for Mindfulness Science Los Angeles California Institute for Advanced Consciousness Studies Santa Monica California Department of Psychiatry and Behavioral Health The Ohio State University College of Medicine Columbus OH United States Normandie University Université de Caen Normandie INSERM U1237 Neuropresage Team Cyceron Caen France Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine of the University of Southern California Los Angeles California Desert-Pacific Mental Illness Research Education and Clinical Center VA San Diego Healthcare System San Diego California Computational Neuroscience Group Center for Brain and Cognition Department of Information and Communication Technologies Universitat Pompeu Fa

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualized meditation practices and designed various meditation interventions that have shown therapeutic efficacy for disorders including depression, pain, addiction, and anxiety. Over the past decade, neuroimaging has been used to examine the neuroscientific basis of meditation practices, effects, states, and outcomes for clinical and nonclinical populations. However, the generalizability and replicability of current neuroscientific models of meditation have not yet been established, because they are largely based on small datasets entrenched with heterogeneity along several domains of meditation (e.g., practice types, meditation experience, clinical disorder targeted), experimental design, and neuroimaging methods (e.g., preprocessing, analysis, task-based, resting-state, structural magnetic resonance imaging). These limitations have precluded a nuanced and rigorous neuroscientific phenotyping of meditation practices and their potential benefits. Here, we present ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)–Meditation, the first worldwide collaborative consortium for neuroscientific investigations of meditation practices. ENIGMA-Meditation will enable systematic meta- and mega-analyses of globally distributed neuroimaging datasets of meditation using shared, standardized neuroimaging methods and tools to improve statistical power and generalizability. Through this powerful collaborative framework, existing neuroscientific accounts of meditation practices can be extended to generate novel and rigorous neuroscientific insights that account for multidomain heterogeneity. ENIGMA-Meditation will inform neuroscientific mechanisms that underlie therapeutic action of meditation practices on psychological and cognitive attributes, thereby advancing the f

关键词： Consortium ENIGMA Magnetic resonance imaging (MRI) Meditation Mindfulness Neuroimaging

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Prediction of COVID-19 Transmission in the United States Using Google Search Trends

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Computers, Materials & Continua 2022年第4期71卷 1751-1768页

作者： Meshrif Alruily Mohamed Ezz Ayman Mohamed Mostafa Nacim Yanes Mostafa Abbas Yasser El-Manzalawy College of Computer and Information Sciences Jouf UniversitySakaka72314Saudi Arabia Faculty of Engineering Al-Azhar UniversityCairo11651Egypt Faculty of Computers and Informatics Zagazig UniversityZagazig44519Egypt RIADI Laboratory La Manouba UniversityManouba2010Tunisia Department of Translational Data Science and Informatics GeisingerDanvillePA17822USA

Accurate forecasting of emerging infectious diseases can guide public health officials in making appropriate decisions related to the allocation of public health *** to the exponential spread of the COVID-19 infection worldwide,several computational models for forecasting the transmission and mortality rates of COVID-19 have been proposed in the *** accelerate scientific and public health insights into the spread and impact of COVID-19,Google released the Google COVID-19 search trends symptoms open-access *** objective is to develop 7 and 14-day-ahead forecasting models of COVID-19 transmission and mortality in the US using the Google search trends for COVID-19 related ***,we propose a stacked long short-term memory(SLSTM)architecture for predicting COVID-19 confirmed and death cases using historical time series data combined with auxiliary time series data from the Google COVID-19 search trends symptoms *** the SLSTM networks trained using historical data only as the base models,our base models for 7 and 14-day-ahead forecasting of COVID cases had the mean absolute percentage error(MAPE)values of 6.6%and 8.8%,*** the other side,our proposed models had improved MAPE values of 3.2%and 5.6%,*** 7 and 14-day-ahead forecasting of COVID-19 deaths,the MAPE values of the base models were 4.8%and 11.4%,while the improved MAPE values of our proposed models were 4.7%and 7.8%,*** found that the Google search trends for“pneumonia,”“shortness of breath,”and“fever”are the most informative search trends for predicting COVID-19 *** also found that the search trends for“hypoxia”and“fever”were the most informative trends for forecasting COVID-19 mortality.

关键词： Forecasting COVID-19 transmission and mortality in the US stacked LSTM SARS-COV-2 and google COVID-19 search trends

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Environment scan of generative AI infrastructure for clinical and translational science

Npj health systems

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Npj health systems 2025年第1期2卷 4页

作者： Betina Idnay Zihan Xu William G Adams Mohammad Adibuzzaman Nicholas R Anderson Neil Bahroos Douglas S Bell Cody Bumgardner Thomas Campion Mario Castro James J Cimino I Glenn Cohen David Dorr Peter L Elkin Jungwei W Fan Todd Ferris David J Foran David Hanauer Mike Hogarth Kun Huang Jayashree Kalpathy-Cramer Manoj Kandpal Niranjan S Karnik Avnish Katoch Albert M Lai Christophe G Lambert Lang Li Christopher Lindsell Jinze Liu Zhiyong Lu Yuan Luo Peter McGarvey Eneida A Mendonca Parsa Mirhaji Shawn Murphy John D Osborne Ioannis C Paschalidis Paul A Harris Fred Prior Nicholas J Shaheen Nawar Shara Ida Sim Umberto Tachinardi Lemuel R Waitman Rosalind J Wright Adrian H Zai Kai Zheng Sandra Soo-Jin Lee Bradley A Malin Karthik Natarajan W Nicholson Price Ii Rui Zhang Yiye Zhang Hua Xu Jiang Bian Chunhua Weng Yifan Peng Department of Biomedical Informatics Columbia University Irving Medical Center New York NY USA. Department of Population Health Sciences Weill Cornell Medicine New York NY USA. Department of Pediatrics Boston Medical Center Boston MA USA Chobanian & Avedisian School of Medicine Boston University Boston MA USA. Oregon Clinical and Translational Research Institute Oregon Health and Science University Portland OR USA. Department of Public Health Sciences University of California Davis Davis CA USA. Keck School of Medicine University of Southern California Los Angeles CA USA. Department of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles CA USA. Department of Pathology and Laboratory Medicine University of Kentucky College of Medicine Lexington KY USA. Clinical and Translational Science Center Weill Cornell Medicine New York NY USA. Division of Pulmonary Critical Care and Sleep Medicine University of Kansas School of Medicine Kansas City KS USA. Department of Biomedical Informatics and Data Science Heersink School of Medicine University of Alabama Birmingham AL USA. Harvard Law School Petrie-Flom Center for Health Law Policy Biotechnology and Bioethics Harvard University Cambridge MA USA. Department of Biomedical Informatics University at Buffalo Buffalo NY USA. Center for Clinical and Translational Science Mayo Clinic Rochester MN USA. Technology and Digital Solutions Stanford Medicine Stanford University Stanford CA USA. Center for Biomedical Informatics Rutgers Cancer Institute New Brunswick NJ USA. Department of Learning Health Sciences University of Michigan Medical School Ann Arbor MI USA. Altman Clinical and Translational Research Institute (ACTRI) University of California San Diego La Jolla CA USA. Department of Biostatistics and Health Data Science School of Medicine Indiana University Indianapolis IN USA. Department of Ophthalmology CCTSI University of Colorado Aurora CO USA. Center for Clinic

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing translational sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers. Our analysis reveals that 53% of institutions identified data security as a primary concern, followed by lack of clinician trust (50%) and AI bias (44%), which must be addressed to ensure the ethical and effective implementation of GenAI technologies.

关键词： Health services Public health

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eCeLLM: Generalizing Large Language Models for E-commerce from Large-scale, High-quality Instruction data 41

eCeLLM: Generalizing Large Language Models for E-commerce fr...

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41st International Conference on Machine Learning, ICML 2024

作者： Peng, Bo Ling, Xinyi Chen, Ziru Sun, Huan Ning, Xia Department of Computer Science and Engineering The Ohio State University United States Translational Data Analytics Institute The Ohio State University United States Department of Biomedical Informatics The Ohio State University United States

With tremendous efforts in developing effective e-commerce models, conventional e-commerce models show limited success in generalist e-commerce modeling, and suffer from unsatisfactory performance on new users and new products - a typical out-of-domain generalization challenge. Meanwhile, large language models (LLMs) demonstrate outstanding performance in generalist modeling and out-of-domain generalizability in many fields. Toward fully unleashing their power for e-commerce, in this paper, we construct ECInstruct, the first open-sourced, large-scale, and high-quality benchmark instruction dataset for e-commerce. Leveraging ECInstruct, we develop eCeLLM, a series of e-commerce LLMs, by instruction-tuning general-purpose LLMs. Our comprehensive experiments and evaluation demonstrate that eCeLLM models substantially outperform baseline models, including the most advanced GPT-4, and the state-of-the-art task-specific models in in-domain evaluation. Moreover, eCeLLM exhibits excellent generalizability to out-of-domain settings, including unseen products and unseen instructions, highlighting its superiority as a generalist e-commerce model. Both the ECInstruct dataset and the eCeLLM models show great potential in empowering versatile and effective LLMs for e-commerce. ECInstruct and eCeLLM models are publicly accessible through https://***/eCeLLM/. Copyright 2024 by the author(s)

关键词： Marketplaces

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Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood

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American Journal of Human Genetics 2025年第2期112卷 276-290页

作者： Jakubek, Yasminka A. Ma, Xiaolong Stilp, Adrienne M. Yu, Fulong Bacon, Jason Wong, Justin W. Aguet, Francois Ardlie, Kristin Arnett, Donna K. Barnes, Kathleen Bis, Joshua C. Blackwell, Tom Becker, Lewis C. Boerwinkle, Eric Bowler, Russell P. Budoff, Matthew J. Carson, April P. Chen, Jiawen Cho, Michael H. Coresh, Josef Cox, Nancy J. de Vries, Paul S. DeMeo, Dawn L. Fardo, David W. Fornage, Myriam Guo, Xiuqing Hall, Michael E. Heard-Costa, Nancy Hidalgo, Bertha Irvin, Marguerite Ryan Johnson, Andrew D. Jorgenson, Eric Kenny, Eimear E. Kessler, Michael D. Levy, Daniel Li, Yun Lima, Joao A.C. Liu, Yongmei Locke, Adam E. Loos, Ruth J.F. Machiela, Mitchell J. Mathias, Rasika A. Mitchell, Braxton D. Murabito, Joanne M. Mychaleckyj, Josyf C. North, Kari E. Orchard, Peter Parker, Stephen C.J. Pershad, Yash Peyser, Patricia A. Pratte, Katherine A. Psaty, Bruce M. Raffield, Laura M. Redline, Susan Rich, Stephen S. Rotter, Jerome I. Shah, Sanjiv J. Smith, Jennifer A. Smith, Aaron P. Smith, Albert Taub, Margaret A. Tiwari, Hemant K. Tracy, Russell Tuftin, Bjoernar Bick, Alexander G. Sankaran, Vijay G. Reiner, Alexander P. Scheet, Paul Auer, Paul L. Department of Internal Medicine University of Kentucky Lexington KY United States Division of Biostatistics Data Science Institute Medical College of Wisconsin Milwaukee WI United States Department of Biostatistics University of Washington Seattle WA United States Division of Hematology/Oncology Boston Children's Hospital Harvard Medical School Boston MA United States Department of Pediatric Oncology Dana-Farber Cancer Institute Harvard Medical School Boston MA United States Broad Institute of MIT and Harvard Cambridge MA United States GMU-GIBH Joint School of Life Sciences The Guangdong-Hong Kong-Macau Joint Laboratory for Cell Fate Regulation and Diseases Guangzhou National Laboratory Guangzhou Medical University Guangzhou China Department of Computer Science Department of Biological Sciences University of Wisconsin Milwaukee Milwaukee WI United States Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX United States Broad Institute Cambridge MA United States University of South Carolina Columbia SC United States Division of Biomedical Informatics and Personalized Medicine School of Medicine School of Medicine University of Colorado Anschutz Medical Campus Aurora CO United States Cardiovascular Health Research Unit Department of Medicine University of Washington Seattle WA United States Department of Biostatistics University of Michigan Ann Arbor MI United States Department of Medicine Division of Cardiology Johns Hopkins Hospital Johns Hopkins University of Medicine Baltimore MD United States Human Genetics Center Department of Epidemiology School of Public Health The University of Texas Health Science Center at Houston Houston TX United States Department of Medicine National Jewish Health Denver CO United States Department of Medicine Division of Cardiology The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center Torrance CA United States Department of Medicine University of

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones. © 2024 The Author(s)

关键词： GWAS mosaic loss of chromosome Y multi-ancestry

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Translation dysregulation in cancer as a source for targetable antigens

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Cancer Cell 2025年第5期43卷 823-840.e18,20页

作者： Weller, Chen Bartok, Osnat McGinnis, Christopher S. Palashati, Heyilimu Chang, Tian-Gen Malko, Dmitry Shmueli, Merav D. Nagao, Asuteka Hayoun, Deborah Murayama, Ayaka Sakaguchi, Yuriko Poulis, Panagiotis Khatib, Aseel Erlanger Avigdor, Bracha Gordon, Sagi Cohen Shvefel, Sapir Zemanek, Marie J. Nielsen, Morten M. Boura-Halfon, Sigalit Sagie, Shira Gumpert, Nofar Yang, Weiwen Alexeev, Dmitry Kyriakidou, Pelgia Yao, Winnie Zerbib, Mirie Greenberg, Polina Benedek, Gil Litchfield, Kevin Petrovich-Kopitman, Ekaterina Nagler, Adi Oren, Roni Ben-Dor, Shifra Levin, Yishai Pilpel, Yitzhak Rodnina, Marina Cox, Jürgen Merbl, Yifat Satpathy, Ansuman T. Carmi, Yaron Erhard, Florian Suzuki, Tsutomu Buskirk, Allen R. Olweus, Johanna Ruppin, Eytan Schlosser, Andreas Samuels, Yardena Department of Molecular Cell Biology Weizmann Institute of Science Rehovot 7610001 Israel Department of Pathology Stanford University Stanford 94305 CA United States Parker Institute for Cancer Immunotherapy San Francisco 94129 CA United States Department of Cancer Immunology Institute for Cancer Research Oslo University Hospital Oslo 0379 Norway Precision Immunotherapy Alliance University of Oslo Oslo Norway Cancer Data Science Laboratory Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda 20892 MD United States Department of Systems Immunology Weizmann Institute of Science Rehovot 7610001 Israel Department of Chemistry and Biotechnology of Engineering The University of Tokyo Tokyo 113-8656 Japan Department of Physical Biochemistry Max Planck Institute for Multidisciplinary Sciences Göttingen 37077 Germany Department of Pathology Sackler School of Medicine Tel Aviv University Tel Aviv 69978 Israel Department of Immunology and Regenerative Biology Weizmann Institute of Science Rehovot 7610001 Israel Computational Systems Biochemistry Research Group Max-Planck Institute of Biochemistry Martinsried 82152 Germany Department of Veterinary Resources Weizmann Institute of Science Rehovot 7610001 Israel Tissue Typing and Immunogenetics Unit Hadassah Hebrew University Hospital Jerusalem 9112102 Israel CRUK Lung Cancer Centre of Excellence University College London Cancer Institute London WC1E 6DD United Kingdom Tumour Immunogenomics and Immunosurveillance Laboratory University College London Cancer Institute London WC1E 6DD United Kingdom Department of Life Science Core Facilities Weizmann Institute of Science Rehovot 7610001 Israel Bioinformatics Unit Department of Life Sciences Core Facilities Weizmann Institute of Science Rehovot 7610001 Israel de Botton Institute for Protein Profiling the Nancy and Stephen Grand Israel National Center for Personalized Medicine Weizmann Institute of Science Rehovot

Aberrant peptides presented by major histocompatibility complex (MHC) molecules are targets for tumor eradication, as these peptides can be recognized as foreign by T cells. Protein synthesis in malignant cells is dysregulated, which may result in the generation and presentation of aberrant peptides that can be exploited for T cell-based therapies. To investigate the role of translational dysregulation in immunological tumor control, we disrupt translation fidelity by deleting tRNA wybutosine (yW)-synthesizing protein 2 (TYW2) in tumor cells and characterize the downstream impact on translation fidelity and immunogenicity using immunopeptidomics, genomics, and functional assays. These analyses reveal that TYW2 knockout (KO) cells generate immunogenic out-of-frame peptides. Furthermore, Tyw2 loss increases tumor immunogenicity and leads to anti-programmed cell death 1 (PD-1) checkpoint blockade sensitivity in vivo. Importantly, reduced TYW2 expression is associated with increased response to checkpoint blockade in patients. Together, we demonstrate that defects in translation fidelity drive tumor immunogenicity and may be leveraged for cancer immunotherapy. © 2025 The Author(s)

关键词： cancer immunopeptidome immune checkpoint blockade neoantigens non-canonical peptides translation fidelity

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Is an Ultra Large Natural Image-Based Foundation Model Superior to a Retina-Specific Model for Detecting Ocular and Systemic Diseases?

arXiv

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arXiv 2025年

作者： Hou, Qingshan Zhou, Yukun Goh, Jocelyn Hui Lin Zou, Ke Yew, Samantha Min Er Srinivasan, Sahana Wang, Meng Lo, Thaddaeus Lei, Xiaofeng Wagner, Siegfried K. Chia, Mark A. Yang, Dawei Jiang, Hongyang Ran, AnRan Santos, Rui Somfai, Gabor Mark Zhou, Juan Helen Chen, Haoyu Chen, Qingyu Cheung, Carol Yim-Lui Keane, Pearse A. Tham, Yih Chung Department of Ophthalmology Yong Loo Lin School of Medicine National University of Singapore Singapore School of Computer Science and Engineering Northeastern University Shenyang China Centre for Innovation and Precision Eye Health Yong Loo Lin School of Medicine National University of Singapore Singapore Centre for Medical Image Computing University College London London United Kingdom NIHR Biomedical Research Centre Moorfields Eye Hospital NHS Foundation Trust London United Kingdom Department of Medical Physics and Biomedical Engineering University College London London United Kingdom Singapore Eye Research Institute Singapore National Eye Centre Singapore Singapore Singapore Institute of Ophthalmology University College London London United Kingdom Department of Ophthalmology and Visual Sciences Chinese University of Hong Kong Hong Kong Department of Ophthalmology Stadtspital Zürich Zurich Switzerland Spross Research Institute Zurich Switzerland Department of Ophthalmology Semmelweis University Budapest Hungary Centre for Sleep and Cognition Centre for Translational MR Research Yong Loo Lin School of Medicine National University of Singapore Singapore Department of Electrical and Computer Engineering National University of Singapore Singapore Joint Shantou International Eye Center Shantou University the Chinese University of Hong Kong Guangdong Shantou China Shantou University Medical College Guangdong Shantou China Department of Biomedical Informatics and Data Science Yale School of Medicine Yale University New Haven United States Duke-NUS Medical School Singapore

The advent of foundation models (FMs) is transforming medical domain. In ophthalmology, RETFound, a retina-specific FM pre-trained sequentially on 1.4 million natural images and 1.6 million retinal images, has demonstrated high adaptability across clinical applications. Conversely, DINOv2, a general-purpose vision FM pre-trained on 142 million natural images, has shown promise in non-medical domains. However, its applicability to clinical tasks remains underexplored. To address this, we conducted head-to-head evaluations by finetuning RETFound and three DINOv2 models (large, base, small) for ocular disease detection and systemic disease prediction tasks, across eight standardized open-source ocular datasets, as well as the Moorfields AlzEye and the UK Biobank datasets. DINOv2-large model outperformed RETFound in detecting diabetic retinopathy (AUROC=0.850–0.952 vs. 0.823-0.944, across three datasets, all P≤0.007) and multi-class eye diseases (AUROC=0.892 vs. 0.846, P Copyright © 2025, The Authors. All rights reserved.

关键词： Ophthalmology

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