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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

AI-based Fog and Edge Computing: A Systematic Review, Taxonomy and Future Directions

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arXiv 2022年

作者： Iftikhar, Sundas Gill, Sukhpal Singh Song, Chenghao Xu, Minxian Aslanpour, Mohammad Sadegh Toosi, Adel N. Du, Junhui Wu, Huaming Ghosh, Shreya Chowdhury, Deepraj Golec, Muhammed Kumar, Mohit Abdelmoniem, Ahmed M. Cuadrado, Felix Varghese, Blesson Rana, Omer Dustdar, Schahram Uhlig, Steve School of Electronic Engineering and Computer Science Queen Mary University of London London United Kingdom University of Kotli Azad Jammu & Kashmir Azad Kashmir Kotli Pakistan Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen China Department of Software Systems and Cybersecurity Faculty of Information Technology Monash University Australia Csiro DATA61 Australia Center for Applied Mathematics Tianjin University Tianjin China The Pennsylvania State University PA United States Naya Raipur India Abdullah Gül University Kayseri Turkey Department of Information Technology National Institute of Technology Jalandhar India Spain School of Computer Science University of St Andrews United Kingdom School of Computer Science and Informatics Cardiff University Cardiff United Kingdom Distributed Systems Group Vienna University of Technology Vienna Austria

Resource management in computing is a very challenging problem that involves making sequential decisions. Resource limitations, resource heterogeneity, dynamic and diverse nature of workload, and the unpredictability of fog/edge computing environments have made resource management even more challenging to be considered in the fog landscape. Recently Artificial Intelligence (AI) and Machine Learning (ML) based solutions are adopted to solve this problem. AI/ML methods with the capability to make sequential decisions like reinforcement learning seem most promising for these type of problems. But these algorithms come with their own challenges such as high variance, explainability, and online training. The continuously changing fog/edge environment dynamics require solutions that learn online, adopting changing computing environment. In this paper, we used standard review methodology to conduct this Systematic Literature Review (SLR) to analyze the role of AI/ML algorithms and the challenges in the applicability of these algorithms for resource management in fog/edge computing environments. Further, various machine learning, deep learning and reinforcement learning techniques for edge AI management have been discussed. Furthermore, we have presented the background and current status of AI/ML-based Fog/Edge Computing. Moreover, a taxonomy of AI/ML-based resource management techniques for fog/edge computing has been proposed and compared the existing techniques based on the proposed taxonomy. Finally, open challenges and promising future research directions have been identified and discussed in the area of AI/ML-based fog/edge computing. Copyright © 2022, The Authors. All rights reserved.

关键词： Edge computing

Decomposition of scattering phase shifts of coupled-channels systems in the complex scaling method

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Physical Review C 2021年第1期104卷 014325-014325页

作者： Myagmarjav Odsuren Takayuki Myo Yuma Kikuchi Manabu Teshigawara Kiyoshi Katō School of Engineering and Applied Sciences and Nuclear Research Center National University of Mongolia Ulaanbaatar 210646 Mongolia General Education Faculty of Engineering Osaka Institute of Technology Osaka 535-8585 Japan Research Center for Nuclear Physics (RCNP) Osaka University Ibaraki 567-0047 Japan Tokuyama College National Institute of Technology Yamaguchi 745-8585 Japan Canon Medical Systems Corporation Otawara 324-8550 Japan Nuclear Reaction Data Centre Faculty of Science Hokkaido University Sapporo 060-0810 Japan

The decomposition of scattering phase shifts in single-channel systems is extended to coupled-channels systems in the complex scaling method. The present method describes the contribution of the resonant states to the phase shift separately from the background in each channel phase shift of the coupled-channels system. We apply this method to the (H3+p)+(He3+n) model for He4, and show that the decomposition of phase shifts in coupled-channels systems provides useful information about the structure of scattering states.

关键词： Nuclear reactions Nuclear structure & decays Resonance reactions Optical, coupled-channel & distorted wave models

Regulating electron diffraction direction with cylindrically symmetric rotating crystal

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arXiv 2022年

作者： Cheng, L. Da, B. Liu, X. Shigeto, K. Tsukagoshi, K. Nabatame, T. Liu, J.W. Zhang, H. Yoshikawa, H. Tanuma, S. Gao, Z.S. Guo, H.X. Sun, Y. Hu, J. Ding, Z.J. Department of Physics University of Science and Technology of China Auhui Hefei230026 China Research and Services Division of Materials Data and Integrated Systems National Institute for Materials Science 1-1 Namiki Ibaraki Tsukuba305-0044 Japan Research Center for Advanced Measurement and Characterization National Institute for Materials Science 1-1 Namiki Ibaraki Tsukuba305-0044 Japan Hitachi High-Tech Corporation Ibaraki Hitachinaka312-8504 Japan National Institute for Materials Science Ibaraki Tsukuba305-0044 Japan Research Center for Functional Materials National Institute for Materials Science 1-1 Namiki Ibaraki Tsukuba305-0044 Japan Institute of Electrical Engineering Chinese Academy of Sciences Beijing100190 China Key Laboratory of MEMS of Ministry of Education School of Electronic Science and Engineering Southeast University Nanjing210096 China Department of Applied Physics and Applied Mathematics Columbia University New YorkNY10027 United States Department of Physics Institute for Nanoscience and Engineering University of Arkansas FayettevilleAR72701 United States

We report a promising InSiO film that allows simultaneous observation of sample morphology and Kikuchi patterns in raster scan mode of scanning electron microscopy. This new experimental observation suggests potential mechanism beyond existing diffraction theories. We find by simulation that this material has a novel cylindrically symmetric rotational crystalline structure that can control the diffraction direction of electrons through a specific rotational distribution of crystal planes, while being independent of the angle and energy of incident electrons within a certain range. © 2022, CC BY-NC-SA.

关键词： Electrons

Banach fixed-point between SEM image and EBSD diffraction pattern from a cylindrically symmetric rotating crystal

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arXiv 2022年

作者： Da, B. Cheng, Long Liu, X. Shigeto, K. Tsukagoshi, K. Nabatame, T. Ding, Z.J. Sun, Y. Hu, J. Liu, J.W. Tang, D.M. Zhang, H. Gao, Z.S. Guo, H.X. Yoshikawa, H. Tanuma, S. Research and Services Division of Materials Data and Integrated Systems National Institute for Materials Science 1-1 Namiki Ibaraki Tsukuba305-0044 Japan Research Center for Advanced Measurement and Characterization National Institute for Materials Science 1-1 Namiki Ibaraki Tsukuba305-0044 Japan Department of Physics University of Science and Technology of China Auhui Hefei230026 China Hitachi High-Tech Corporation Ibaraki Hitachinaka312-8504 Japan National Institute for Materials Science Ibaraki Tsukuba305-0044 Japan University of Science and Technology of China Anhui Hefei230026 China Department of Applied Physics and Applied Mathematics Columbia University New YorkNY10027 United States Department of Physics Institute for Nanoscience and Engineering University of Arkansas FayettevilleAR72701 United States Research Center for Functional Materials National Institute for Materials Science 1-1 Namiki Ibaraki Tsukuba305-0044 Japan Institute of Electrical Engineering Chinese Academy of Sciences Beijing100190 China Key Laboratory of MEMS of Ministry of Education School of Electronic Science and Engineering Southeast University Nanjing210096 China

The Kikuchi bands arise from Bragg diffraction of incoherent electrons scattered within a crystalline specimen and can be observed in both the transmission and reflection modes of scanning electron microscopy (SEM). Converging, rocking, or grazing incidence beams must be used to generate divergent electron sources to obtain the Kikuchi pattern. This paper report the observation of Kikuchi pattern from SEM images of an exceptional rotating crystal with continuous rotation in the local crystal direction and satisfying cylindrical symmetry, named a cylindrically symmetric rotating crystal. SEM images of cylindrically symmetric rotating crystals reflect the interactions between electrons and the sample in both the real- and momentum-space. Furthermore, we identify an unexpected mathematical relationship between the electron backscattered diffraction (EBSD) Kikuchi pattern matrix map and the SEM image of the present sample which can be rationalized as a concrete example of the Banach fixed-point theorems in the field of EBSD technique. © 2022, CC BY-NC-SA.

关键词： Electrons

Black-box optimization for integer-variable problems using Ising machines and factorization machines

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arXiv 2022年

作者： Seki, Yuya Tamura, Ryo Tanaka, Shu Graduate School of Science and Technology Keio University Kanagawa223-8522 Japan National Institute for Materials Science Ibaraki305-0044 Japan Research and Services Division of Materials Data and Integrated System National Institute for Materials Science 1-1 Namiki Tsukuba-city Ibaraki305-0044 Japan Graduate School of Frontier Sciences The University of Tokyo Chiba277-8568 Japan Department of Applied Physics and Physico-Informatics Keio University Kanagawa223-8522 Japan Quantum Computing Center Keio University Kanagawa223-8522 Japan Green Computing System Research Organization Waseda University Tokyo162-0042 Japan Quantum Computing Unit Institute of Innovative Research Tokyo Institute of Technology Tokyo105-0023 Japan

Black-box optimization has potential in numerous applications such as hyperparameter optimization in machine learning and optimization in design of experiments. Ising machines are useful for binary optimization problems because variables can be represented by a single binary variable of Ising machines. However, conventional approaches using an Ising machine cannot handle black-box optimization problems with non-binary values. To overcome this limitation, we propose an approach for integer-variable black-box optimization problems by using Ising/annealing machines and factorization machines in cooperation with three different integer-encoding methods. The performance of our approach is numerically evaluated with different encoding methods using a simple problem of calculating the energy of the hydrogen molecule in the most stable state. The proposed approach can calculate the energy using any of the integer-encoding methods. However, one-hot encoding is useful for problems with a small size. Copyright © 2022, The Authors. All rights reserved.

关键词： Machine learning

Coupled Chemical Reactions: Effects of Electric Field, Diffusion and Boundary Control

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arXiv 2023年

作者： Xu, Shixin Eisenberg, Robert Song, Zilong Huang, Huaxiong Zu Chongzhi Center for Mathematics and Computational Sciences Duke Kunshan University 8 Duke Ave Jiangsu Kunshan China Department of Applied Mathematics Illinois Institute of Technology ChicagoIL60616 United States Department of Physiology and Biophysics Rush University Chicago IL60612 United States Math and Statistics Department Utah State University Old Main Hill Logan UT84322 United States Research Center for Mathematics Advanced Institute of Natural Sciences Beijing Normal University Guangdong Zhuhai519088 China Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science BNU-HKBU United International College Guangdong Zhuhai519088 China Laboratory of Mathematics and Complex Systems MOE Beijing Normal University Beijing100875 China Department of Mathematics and Statistics York University TorontoONM3J 1P3 Canada

MSC Codes 92E20, 92B05, 35Q92Chemical reactions involve the movement of charges, and this work presents a mathematical model for describing chemical reactions in electrolytes. The model is developed using an energy variational method that aligns with classical thermodynamics principles. It encompasses both electrostatics and chemical reactions within consistently defined energetic and dissipative functionals. Furthermore, the energy variation method is extended to account for open systems that involve the input and output of charge and mass. Such open systems have the capability to convert one form of input energy into another form of output energy. In particular, a two-domain model is developed to study a reaction system with self-regulation and internal switching, which plays a vital role in the electron transport chain of mitochondria responsible for ATP generation-a crucial process for sustaining life. Simulations are conducted to explore the influence of electric potential on reaction rates and switching dynamics within the two-domain system. It shows that the electric potential inhibits the oxidation reaction while accelerating the reduction reaction. © 2023, CC BY.

关键词： Open systems

P18.04.B SINGLE CELL TRANSCRIPTOMIC ANALYSIS IDENTIFIES DISTINCT INTRATUMORAL SUBCLONES IN MENINGIOMA

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Neuro-Oncology 2023年第SUPPLEMENT_2期25卷 ii122–ii122页

作者： Blume, C Tang, Y Dogan, H Ritter, M Dentro, S von Deimling, A Gerstung, M Schlesner, M Sahm, F Maas, S L N University Hospital Heidelberg Dept. of Neuropathology Heidelberg Germany German Cancer Research Center (DKFZ) German Consortium for Translational Cancer Research (DKTK) Clinical Cooperation Unit Neuropathology Heidelberg Germany Division of AI in Oncology German Cancer Research Center (DKFZ) Heidelberg Germany European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Hinxton United Kingdom Biomedical Informatics Data Mining and Data Analytics Faculty of Applied Computer Science and Medical Faculty University of Augsburg Augsburg Germany Department of Pathology Leiden University Medical Center Leiden Netherlands Department of Pathology Erasmus Medical Center Rotterdam Netherlands

Redefining pandemic preparedness:Multidisciplinary insights from the CERP modelling workshop in infectious diseases,workshop report

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Infectious Disease Modelling 2024年第2期9卷 501-518页

作者： Marta C.Nunes Edward Thommes Holger Fröhlich Antoine Flahault Julien Arino Marc Baguelin Matthew Biggerstaff Gaston Bizel-Bizellot Rebecca Borchering Giacomo Cacciapaglia Simon Cauchemez Alex Barbier-Chebbah Carsten Claussen Christine Choirat Monica Cojocaru Catherine Commaille-Chapus Chitin Hon Jude Kong Nicolas Lambert Katharina B.Lauer Thorsten Lehr Cédric Mahe Vincent Marechal Adel Mebarki Seyed Moghadas Rene Niehus Lulla Opatowski Francesco Parino Gery Pruvost Andreas Schuppert Rodolphe Thiébaut Andrea Thomas-Bachli Cecile Viboud Jianhong Wu Pascal Crépey Laurent Coudeville Center of Excellence in Respiratory Pathogens(CERP) Hospices Civils de Lyon(HCL)and Centre International de Recherche en Infectiologie(CIRI)Équipe SantéPubliqueÉpidémiologie etÉcologieÉvolutive des Maladies Infectieuses(PHE3ID)Inserm U1111CNRS UMR5308ENS de LyonUniversitéClaude Bernard Lyon 1LyonFrance South African Medical Research Council Vaccines&Infectious Diseases Analytics Research UnitFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa New Products and Innovation(NPI) Sanofi Vaccines(Global)TorontoOntarioCanada Department of Mathematics and Statistics University of GuelphGuelphOntarioCanada Fraunhofer Institute for Algorithms and Scientific Computing(SCAI) Department of BioinformaticsSchloss BirlinghovenSankt AugustinGermany University of Bonn Bonn-Aachen International Center for IT(b-it)BonnGermany Institute of Global Health Faculty of MedicineUniversity of GenevaGenevaSwitzerland and Swiss School of Public HealthZürichSwitzerland Department of Mathematics University of ManitobaWinnipegManitobaCanada MRC Centre for Global Infectious Disease Analysis School of Public HealthImperial College LondonLondonUK Centre for Mathematical Modelling of Infectious Diseases Department of Infectious Disease EpidemiologyLondon School of Hygiene&Tropical MedicineLondonUK National Center for Immunization and Respiratory Diseases(NCIRD) US Centers for Disease Control and Prevention(CDC)AtlantaGAUSA Departement of Computational Biology Departement of Global HealthInstitut PasteurParisFrance Institut de Physique des Deux Infinis de Lyon(IP2I) UMR5822IN2P3/CNRSUniversitéClaude Bernard Lyon 1VilleurbanneFrance Mathematical Modelling of Infectious Diseases Unit Institut PasteurUniversitéParis CitéUMR2000 CNRSParisFrance Decision and Bayesian Computation Institut PasteurUniversitéParis CitéCNRS UMR 3571France Fraunhofer-Institute for Translational Medicine and Pharmacology HamburgGermany Institute of Global Health Faculty of MedicineUniversity of

In July 2023,the center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 *** report summarizes the rich discussions that occurred during the *** workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data,social media,and wastewater *** advancements were noted in the development of predictive models,with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease *** role of open collaboration between various stakeholders in modelling was stressed,advocating for the continuation of such partnerships beyond the pandemic.A major gap identified was the absence of a common international framework for data sharing,which is crucial for global pandemic ***,the workshop underscored the need for robust,adaptable modelling frameworks and the integration of different data sources and collaboration across sectors,as key elements in enhancing future pandemic response and preparedness.

关键词： Modelling Covid-19 Infectious diseases Pandemic preparedness Workshop