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arXiv 2024年

作者： Šubjak, Jan Gandolfi, Davide Goffo, Elisa Rapetti, David Jankowski, Dawid Mizuki, Toshiyuki Dai, Fei Serrano, Luisa M. Wilson, Thomas G. Goździewski, Krzysztof Nowak, Grzegorz Jenkins, Jon M. Twicken, Joseph D. Winn, Joshua N. Bieryla, Allyson Ciardi, David R. Cochran, William D. Collins, Karen A. Deeg, Hans J. Garcia, Rafael A. Guenther, Eike W. Hatzes, Artie P. Kabath, Petr Korth, Judith Latham, David W. Livingston, John H. Lund, Michael B. Mathur, Savita Narita, Norio Orell-Miquel, Jaume Palle, Enric Persson, Carina M. Redfield, Seth Schwarz, Richard P. Watanabe, David Ziegler, Carl Astronomical Institute Czech Academy of Sciences Fričova 298 Ondřejov251 65 Czech Republic Center for Astrophysics | Harvard & Smithsonian 60 Garden Street CambridgeMA02138 United States Dipartimento di Fisica Universita degli Studi di Torino via Pietro Giuria 1 TorinoI-10125 Italy Thuringer Landessternwarte Tautenburg Sternwarte 5 Tautenburg07778 Germany NASA Ames Research Center Moffett FieldCA94035 United States Research Institute for Advanced Computer Science Universities Space Research Association WashingtonDC20024 United States Institute of Astronomy Faculty of Physics Astronomy and Informatics Nicolaus Copernicus University Grudziadzka 5 Toruń87-100 Poland Astrobiology Center of NINS 2-21-1 Osawa Mitaka Tokyo181-8588 Japan National Astronomical Observatory of Japan 2-21-2 Osawa Mitaka Tokyo181-8588 Japan Institute for Astronomy University of Hawai'i 2680 Woodlawn Drive HonoluluHI96822 United States Department of Physics University of Warwick Gibbet Hill Road CoventryCV4 7AL United Kingdom SETI Institute Mountain ViewCA94043 United States Department of Astrophysical Sciences Princeton University PrincetonNJ08544 United States NASA Exoplanet Science Institute-Caltech/IPAC PasadenaCA91125 United States McDonald Observatory The University of Texas AustinTX United States Center for Planetary Systems Habitability The University of Texas AustinTX United States C. Via Lactea S/N Tenerife La LagunaE-38205 Spain Dept. de Astrofisica Tenerife La LagunaE-38206 Spain Universite Paris-Saclay Universite Paris Cite CEA CNRS AIM Gif-sur-Yvette91191 France Lund Observatory Division of Astrophysics Department of Physics Lund University Box 118 Lund22100 Sweden Astronomical Science Program Graduate University for Advanced Studies SOKENDAI 2-21-1 Osawa Mitaka Tokyo181-8588 Japan Komaba Institute for Science The University of Tokyo 3-8-1 Komaba Meguro Tokyo153-8902 Japan Chalmers University of Technology Departmen

We report on the discovery and spectroscopic confirmation of TOI-2458 b, a transiting mini-Neptune around an F-type star leaving the mainsequence with a mass of M*= 1.05 ± 0.03Mo, a radius of R*= 1.31 ± 0.03 Ro, an effective temperature of Teff = 6005 ± 50 K, and a metallicity of -0.10 ± 0.05 dex. By combining TESS photometry with high-resolution spectra acquired with the HARPS spectrograph, we found that the transiting planet has an orbital period of ∼3.74 days, a mass of Mp = 13.31±0.99M⊕ and a radius of Rp = 2.83±0.20 R⊕. The host star TOI-2458 shows a short activity cycle of ∼54 days revealed in the HARPS S-index and Hα times series. We took the opportunity to investigate other F stars showing activity cycle periods comparable to that of TOI-2458 and found that they have shorter rotation periods than would be expected based on the gyrochronology predictions. In addition, we determined TOI-2458's stellar inclination angle to be i*= 10.6+13.3 -10.6 degrees. We discuss that both phenomena (fast stellar rotation and planet orbit inclination) could be explained by in situ formation of a hot Jupiter interior to TOI-2458 b. It is plausible that this hot Jupiter was recently engulfed by the star. Analysis of HARPS spectra has identified the presence of another planet with a period of P = 16.55 ± 0.06 days and a minimum mass of Mp sin i = 10.22 ± 1.90M⊕. Using dynamical stability analysis, we constrained the mass of this planet to the range Mc (10, 25)M⊕. © 2024, CC BY.

关键词： Stars

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Retracted: Sylabus and Matrials Design for Vocational Student and Its Dissemination Using Website

Retracted: Sylabus and Matrials Design for Vocational Studen...

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2018 Workshop on Multidisciplinary and Its Applications: Applied Mathematics, computer science, Information Systems, and Information Technology, WMA-Mathcomtech 2018

作者： Harahap, Astro Julida Ongko, Erianto Manurung, Hotler Kurnia, Dian Hartono, H. Abdullah, Dahlan Erliana, Cut Ita Djanggih, Hardianto Saddhono, Kundharu Rianita, Dian Setiawan, Muhammad Ikhsan Setiawan, Yuliyanto Budi Manurung, Rosida Tiurma Sriadhi, S. Sinurat, Mangasi Siregar, Aisyah Soni Hutauruk, Rapat Piter Sibarani, Nico Benjamain Department of Informatics Akademi Teknologi Industri Immanuel Medan Indonesia Department of Computer Systems Universitas Pancabudi Medan Indonesia Department of Computer Science STMIK IBBI Medan Indonesia Department of Informatics Universitas Malikussaleh Aceh Indonesia Department of Industrial Engineering Universitas Malikussaleh Aceh Indonesia Department of Law Universitas Tompotika Luwuk Banggai Indonesia Graduate Program Universitas Sebelas Maret Surakarta Indonesia Department of Administration University of Lancang Kuning Pekanbaru Indonesia Department of Civil Engineering Narotama University Surabaya Indonesia Study Program of Communication Studies Universitas Semarang Indonesia Graduate Program in Scientific Psychology Universitas Kristen Maranatha Indonesia Department of Electrical Engineering Universitas Negeri Medan Indonesia STIE Bina Karya Tebing Tinggi Indonesia

The learners' needs are an important factor in designing syllabus and materials design, this research deals with the syllabus and material design based on the professional's needs. It is expected that the syllabus and materials designes are communicatively applicable to the professional academy. Descriptive method is applied in this research. The sample of this research is 30 students of ATII Immanuel Academy Medan. They were selected by random sampling to get the data, the questioners were administered to students. the questioners consisted of 54 items and the semi structured interview consisted of 5 questions, the finding indicated that learners' needs were focused on reading and speaking skills. With reference appropriately and proportionally derived for students of the Professional Academy. Further on the basis of the syllabus, materials are designed in which the skills of using language become a priority. The results of this research will be disseminated using the website. © Published under licence by IOP Publishing Ltd.

关键词： Information systems

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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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Generation of terahertz transients from Co2Fe0.4Mn0.6Si-Heusler-alloy/normal-metal nanobilayers excited by femtosecond optical pulses

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Physical Review Research 2021年第4期3卷 043025-043025页

作者： Sarah Heidtfeld Roman Adam Takahide Kubota Koki Takanashi Derang Cao Carolin Schmitz-Antoniak Daniel E. Bürgler Fangzhou Wang Christian Greb Genyu Chen Ivan Komissarov Hilde Hardtdegen Martin Mikulics Roman Sobolewski Shigemasa Suga Claus M. Schneider Research Centre Jülich Peter Grünberg Institute 52425 Jülich Germany Faculty of Physics University of Duisburg-Essen 47048 Duisburg Germany Institute for Materials Research Tohoku University Sendai 980-8577 Japan Center for Spintronics Research Network Tohoku University Sendai 980-8577 Japan Center for Science and Innovation in Spintronics (Core Research Cluster) Tohoku University Sendai 980-8577 Japan College of Physics National Demonstration Center for Experimental Applied Physics Education Qingdao University Qingdao 266071 China Materials Science Graduate Program University of Rochester Rochester New York 14627 USA Laboratory for Laser Energetics University of Rochester Rochester New York 14623 USA Department of Electrical and Computer Engineering University of Rochester Rochester New York 14627 USA Belarusian State University of Informatics and Radioelectronics Minsk 220013 Belarus Research Centre Jülich Ernst Ruska Centre for Microscopy and Spectroscopy with Electrons 52425 Jülich Germany Department of Physics and Astronomy University of Rochester Rochester New York 14627 USA The Institute of Scientific and Industrial Research Osaka University Ibaraki Osaka 567-0047 Japan Department of Physics University of California Davis Davis California 95616 USA

We generated pulses of electromagnetic radiation in the terahertz (THz) frequency range by optical excitation of Co2Fe0.4Mn0.6Si (CFMS)/normal-metal (NM) bilayer structures. The CFMS is a Heusler alloy showing a band gap in one spin channel and is therefore a half metal. We compared the THz emission efficiency in a systematic manner for four different CFMS/NM bilayers, where NM was either Pt, Ta, Cr, or Al. Our measurements show that the THz intensity is highest for a Pt capping. We also demonstrate the tunability of the THz amplitude by varying the magnetic field for all four bilayers. We attribute the THz generation to the inverse spin Hall effect. In order to investigate the role of the interface in THz generation, we measured the spin mixing conductance for each CFMS/NM bilayer using a ferromagnetic resonance method. We found that the spin-orbit coupling cannot completely describe the THz generation in the bilayers and that the spin transmission efficiency of the CFMS/NM interface and the spin diffusion length, as well as the oxidation of the NM layer, play crucial roles in the THz emission process.

关键词： Inverse spin Hall effect Magnetism Spin injection Spin pumping Spintronics Ferromagnetic resonance Terahertz time-domain spectroscopy

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A Neuro-Inspired Approach to Solve a Simultaneous Location and Mapping Task Using Shared Information in Multiple Robots Systems 15

A Neuro-Inspired Approach to Solve a Simultaneous Location a...

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15th International Conference on Control, Automation, Robotics and Vision, ICARCV 2018

作者： Menezes, Matheus Chaves De Freitas, Edison Pignaton Cheng, Sen De Oliveira, Alexandre Cesar Muniz De Almeida Ribeiro, Paulo Rogerio Graduate Program on Computer Science Federal University of Maranhão Sao Luis Brazil Computational Neuroscience Ruhr University Bochum Institute for Neural Computation Bochum Germany Department of Informatics Federal University of Maranhão Sao Luis Maranhao Brazil Department of Computer Engineering Federal University of Maranhão Sao Luis Maranhao Brazil

ISBN: (纸本)9781538695821

This paper presents a neuro-inspired mapping approach that uses partial information shared by multiple robots to reduce the time to create a map of an entire environment. Robots using a neurobiologically inspired algorithm, namely RatSLAM, map an environment sharing video information among themselves. RatSLAM, which is based on the navigation system present in the hippocampus of rodents' brain, has been widely used on simultaneous localization and mapping (SLAM) problem. This proposal has been able to generate suitable maps mainly when there is redundant information, e.g. a scene is seen more than once, since this fact activates local view cells that inject activity inside the pose cells via an excitatory link. The work here reported extends this approach by merging partial information acquired by multiple robots. The results from the performed experiments show that the final map built by two robots with shared information is similar to one built by two robots performing the same mapping task individually, i.e. without sharing information. However, the time spent to generate the whole map with the proposed shared approach was smaller than the one without the shared information. Thus, the current approach allows creating a complete map of an environment within a reduced time using multiple robots. © 2018 IEEE.

关键词： Mapping

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Rainfall forecasting using PSPline and rice production with ocean-atmosphere interaction 2

Rainfall forecasting using PSPline and rice production with ...

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2nd International Conference on Eco engineering Development 2018, ICEED 2018

作者： Caraka, Rezzy Eko Supatmanto, Budi Darmawan Tahmid, Muhammad Soebagyo, Joko Mauludin, M. Ali Iskandar, Akbar Pardamean, Bens Bina Nusantara University Jakarta11480 Indonesia Indonesia Indonesia Agency for Meteorology Climatology and Geophysics Indonesia College of Technology Wastukancana Purwakarta Indonesia Laboratory of Sociology and Extension Padjadjaran University Indonesia Informatics Engineering STMIK AKBA Makassar Indonesia Computer Science Department BINUS Graduate Program - Master of Computer Science Bina Nusantara University Jakarta11480 Indonesia

The role of climate can be affected by plants. The weather can accelerate and multiply the existence of various plant pests and diseases, accelerate the growth and development of grass among plants, and encourage the emergence of infection and significant damage to plants. The elements of climate that affect the growth of plants are one of them is rainfall. In this paper, we performed the simulation using the non-parametric penalized spline (PSPLINE) method and studied the effect on rice production in Lampung. It can be concluded that the increasing fluctuation, frequency, and intensity of climate anomalies in the last decade caused by the ENSO phenomenon have an impact on changes in distribution patterns, intensity, and period of the wet season so that the start of the rainy season and the dry season becomes too late. As a result, there is a seasonal shift from normal average conditions that can ultimately have severe implications for food crops. In a nutshell penalized spline gives high accuracy with R 2 = 96.227% and MAPE = 1.62%. © 2018 Institute of Physics Publishing. All rights reserved.

关键词： Rain

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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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The repertoire of mutational signatures in human cancer (vol 578, pg 94, 2020)

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NATURE 2023年第7948期614卷 E41-E41页

作者： Alexandrov, Ludmil B. Kim, Jaegil Haradhvala, Nicholas J. Huang, Mi Ni Ng, Alvin Wei Tian Wu, Yang Boot, Arnoud Covington, Kyle R. Gordenin, Dmitry A. Bergstrom, Erik N. Islam, S. M. Ashiqul Lopez-Bigas, Nuria Klimczak, Leszek J. McPherson, John R. Morganella, Sandro Sabarinathan, Radhakrishnan Wheeler, David A. Mustonen, Ville Getz, Gad Rozen, Steven G. Stratton, Michael R. Department of Cellular and Molecular Medicine Department of Bioengineering Moores Cancer Center University of California San Diego CA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Cellular and Molecular Medicine and Department of Bioengineering University of California San Diego La Jolla CA USA UC San Diego Moores Cancer Center San Diego CA USA University of California San Diego San Diego CA USA Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Massachusetts General Hospital Boston MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Laboratory for Medical Science Mathematics RIKEN Center for Integrative Medical Sciences Yokohama Japan Computational Biology Program Ontario Institute for Cancer Research Toronto ON Canada Programme in Cancer & Stem Cell Biology Duke-NUS Medical School Singapore Singapore Centre for Computational Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Singapore Programme in Cancer and Stem Cell Biology Centre for Computational Biology Duke-NUS Medical School Singapore Singapore SingHealth Duke-NUS Institute of Precision Medicine National Heart Centre Singapore Singapore Singapore Cancer Science Institute of Singapore National University of Singapore Singapore Singapore Institute of Molecular and Cell Biology Singapore Singapore Laboratory of Cancer Epigenome Division of Medical Science National Cancer Centre Singapore Singapore Singapore Duke-NUS Medical School Singapore Singapore Human Genome Sequencing Center Baylor College of Medicine Houston TX USA Dan L. Duncan Cancer Center Baylor College of Medicine Houston TX USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA Genome Integrity and Structural Biology Laboratory National Ins

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Polygenic enrichment distinguishes disease associations of individual cells in single-cell RNA-seq data

Research Square

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Research Square 2021年

作者： Zhang, Martin Jinye Hou, Kangcheng Pasaniuc, Bogdan Price, Alkes L. Dey, Kushal K. Jagadeesh, Karthik A. Weinand, Kathryn Sakaue, Saori Taychameekiatchai, Aris Rao, Poorvi Pisco, Angela Oliveira Zou, James Wang, Bruce Gandal, Michael Raychaudhuri, Soumya Harvard University United States Osaka University Japan Department of Epidemiology Harvard T.H. Chan School of Public Health BostonMA United States Program in Medical and Population Genetics Broad Institute of MIT and Harvard CambridgeMA United States Bioinformatics Interdepartmental Program University of California Los Angeles Los AngelesCA United States Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Department of Computational Medicine David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Center for Data Sciences Brigham and Women’s Hospital BostonMA United States Division of Genetics Department of Medicine Brigham and Women’s Hospital Harvard Medical School BostonMA United States Division of Rheumatology Inflammation and Immunity Department of Medicine Brigham and Women’s Hospital Harvard Medical School BostonMA United States Department of Biomedical Informatics Harvard Medical School BostonMA United States Department of Medicine and Liver Center University of California San Francisco San FranciscoCA United States Developmental and Stem Cell Biology Graduate Program University of California San Francisco San FranciscoCA United States Chan Zuckerberg Biohub San FranciscoCA United States Department of Electrical Engineering Stanford University Palo AltoCA United States Department of Biomedical Data Science Stanford University Palo AltoCA United States Department of Psychiatry David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Program in Neurobehavioral Genetics Semel Institute David Geffen School of Medicine University of California Los Angeles Los AngelesCA United States Versus Arthritis Centre for Genetics and Genomic

Gene expression at the individual cell-level resolution, as quantified by single-cell RNA-sequencing (scRNA-seq), can provide unique insights into the pathology and cellular origin of diseases and complex traits. Here, we introduce single-cell Disease Relevance Score (scDRS), an approach that links scRNA-seq with polygenic risk of disease at individual cell resolution;scDRS identifies individual cells that show excess expression levels for genes in a disease-specific gene set constructed from GWAS data. We determined via simulations that scDRS is well-calibrated and powerful in identifying individual cells associated to disease. We applied scDRS to GWAS data from 74 diseases and complex traits (average N =341K) in conjunction with 16 scRNA-seq data sets spanning 1.3 million cells from 31 tissues and organs. At the cell type level, scDRS broadly recapitulated known links between classical cell types and disease, and also produced novel biologically plausible findings. At the individual cell level, scDRS identified subpopulations of disease-associated cells that are not captured by existing cell type labels, including subpopulations of CD4+ T cells associated with inflammatory bowel disease, partially characterized by their effector-like states;subpopulations of hippocampal CA1 pyramidal neurons associated with schizophrenia, partially characterized by their spatial location at the proximal part of the hippocampal CA1 region;and subpopulations of hepatocytes associated with triglyceride levels, partially characterized by their higher ploidy levels. At the gene level, we determined that genes whose expression across individual cells was correlated with the scDRS score (thus reflecting co-expression with GWAS disease genes) were strongly enriched for gold-standard drug target and Mendelian disease genes. © 2021, CC BY.

关键词： RNA

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The evolutionary history of 2,658 cancers (vol 578, pg 122, 2020)

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NATURE 2023年第7948期614卷 E42-E42页

作者： Gerstung, Moritz Jolly, Clemency Leshchiner, Ignaty Dentro, Stefan C. Gonzalez, Santiago Rosebrock, Daniel Mitchell, Thomas J. Rubanova, Yulia Anur, Pavana Yu, Kaixian Tarabichi, Maxime Deshwar, Amit Wintersinger, Jeff Kleinheinz, Kortine Vazquez-Garcia, Ignacio Haase, Kerstin Jerman, Lara Sengupta, Subhajit Macintyre, Geoff Malikic, Salem Donmez, Nilgun Livitz, Dimitri G. Cmero, Marek Demeulemeester, Jonas Schumacher, Steven Fan, Yu Yao, Xiaotong Lee, Juhee Schlesner, Matthias Boutros, Paul C. Bowtell, David D. Zhu, Hongtu Getz, Gad Imielinski, Marcin Beroukhim, Rameen Sahinalp, S. Cenk Ji, Yuan Peifer, Martin Markowetz, Florian Mustonen, Ville Yuan, Ke Wang, Wenyi Morris, Quaid D. Spellman, Paul T. Wedge, David C. Van Loo, Peter European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Cambridge UK European Molecular Biology Laboratory Genome Biology Unit Heidelberg Germany Wellcome Sanger Institute Cambridge UK Genome Biology Unit European Molecular Biology Laboratory (EMBL) Heidelberg Germany University of Ljubljana Ljubljana Slovenia The Francis Crick Institute London UK Big Data Institute University of Oxford Oxford UK Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Big Data Institute Li Ka Shing Centre University of Oxford Oxford UK University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Department of Applied Mathematics and Theoretical Physics Centre for Mathematical Sciences University of Cambridge Cambridge UK Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA Department of Statistics Columbia University New York NY USA Department of Haematology University of Cambridge Cambridge UK University of Leuven Leuven Belgium Broad Institute of MIT and Harvard Cambridge MA USA Center for Cancer Research Massachusetts General Hospital Charlestown MA USA Department of Pathology Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Center for Cancer Research Massachusetts General Hospital Boston MA USA Dana-Farber Cancer Institute Boston MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Oxford NIHR Biomedical Research Centre Oxford UK Oxford NIHR Biomedical Research Centre University of Oxford Oxford UK University of Toronto Toronto Ontario Canada Vector Institute Toronto Ontario Canada Vector Institute Toronto ON Canada Department of Computer Science University of Toronto Toronto ON Canada Ontario Institute for Cancer Research Toronto Ontario Canada University of California Los Angeles

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