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Identifying the best machine learning algorithms for brain tumor segmentation, progression assessment, and overall survival prediction in the BRATS challenge

arXiv

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arXiv 2018年

作者： Bakas, Spyridon Reyes, Mauricio Jakab, Andras Bauer, Stefan Rempfler, Markus Crimi, Alessandro Shinohara, Russell Takeshi Berger, Christoph Ha, Sung Min Rozycki, Martin Prastawa, Marcel Alberts, Esther Lipkova, Jana Freymann, John Kirby, Justin Bilello, Michel Fathallah-Shaykh, Hassan M. Wiest, Roland Kirschke, Jan Wiestler, Benedikt Colen, Rivka Kotrotsou, Aikaterini Lamontagne, Pamela Marcus, Daniel Milchenko, Mikhail Nazeri, Arash Weber, Marc-Andr Mahajan, Abhishek Baid, Ujjwal Gerstner, Elizabeth Kwon, Dongjin Acharya, Gagan Agarwal, Manu Alam, Mahbubul Albiol, Alberto Albiol, Antonio Albiol, Francisco J. Alex, Varghese Allinson, Nigel Amorim, Pedro H.A. Amrutkar, Abhijit Anand, Ganesh Andermatt, Simon Arbel, Tal Arbelaez, Pablo Avery, Aaron Azmat, Muneeza Pranjal, B. Bai, Wenjia Banerjee, Subhashis Barth, Bill Batchelder, Thomas Batmanghelich, Kayhan Battistella, Enzo Beers, Andrew Belyaev, Mikhail Bendszus, Martin Benson, Eze Bernal, Jose Bharath, Halandur Nagaraja Biros, George Bisdas, Sotirios Brown, James Cabezas, Mariano Cao, Shilei Cardoso, Jorge M. Carver, Eric N. Casamitjana, Adri Castillo, Laura Silvana Cat, Marcel Cattin, Philippe Cérigues, Albert Chagas, Vinicius S. Chandra, Siddhartha Chang, Yi-Ju Chang, Shiyu Chang, Ken Chazalon, Joseph Chen, Shengcong Chen, Wei Chen, Jefferson W. Chen, Zhaolin Cheng, Kun Choudhury, Ahana Roy Chylla, Roger Clrigues, Albert Colleman, Steven Colmeiro, Ramiro German Rodriguez Combalia, Marc Costa, Anthony Cui, Xiaomeng Dai, Zhenzhen Dai, Lutao Daza, Laura Alexandra Deutsch, Eric Ding, Changxing Dong, Chao Dong, Shidu Dudzik, Wojciech Eaton-Rosen, Zach Egan, Gary Escudero, Guilherme Estienne, Tho Everson, Richard Fabrizio, Jonathan Fan, Yong Fang, Longwei Feng, Xue Ferrante, Enzo Fidon, Lucas Fischer, Martin French, Andrew P. Fridman, Naomi Fu, Huan Fuentes, David Gao, Yaozong Gates, Evan Gering, David Gholami, Amir Gierke, Willi Glocker, Ben Gong, Mingming Gonzlez-Vill, Sandra Grosges, T. Guan, Yuanfang Guo, Sheng Gupta, Sudeep Han, Woo-Sup Han, Il Song Harmuth, Ko Center for Biomedical Image Computing and Analytics University of Pennsylvania PhiladelphiaPA United States Department of Radiology Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania PhiladelphiaPA United States Institute for Surgical Technology and Biomechanics University of Bern Bern Switzerland Center for MR-Research University Children's Hospital Zurich Zurich Switzerland Support Centre for Advanced Neuroimaging Inselspital Institute for Diagnostic and Interventional Neuroradiology Bern University Hospital Bern Switzerland University Hospital of Zurich Zurich Switzerland Center for Clinical Epidemiology and Biostatistics University of Pennsylvania Philadelphia United States Image-Based Biomedical Modeling Group Technical University of Munich Munich Germany Icahn School of Medicine Mount Sinai Health System New YorkNY United States Leidos Biomedical Research Inc. Frederick National Laboratory for Cancer Research FrederickMD21701 United States Cancer Imaging Program National Cancer Institute National Institutes of Health BethesdaMD20814 United States Department of Neurology University of Alabama at Birmingham BirminghamAL United States Department of Diagnostic Radiology University of Texas MD Anderson Cancer Center HoustonTX United States Department of Psychology Washington University St. LouisMO United States Neuroimaging Informatics and Analysis Center Washington University St. LouisMO United States Department of Radiology Washington University St. LouisMO United States Institute of Diagnostic and Interventional Radiology Pediatric Radiology and Neuroradiology University Medical Center Rostock Ernst-Heydemann-Str. 6 Rostock18057 Germany Tata Memorial Centre Homi Bhabha National Institute Mumbai India Shri Guru Gobind Singhji Institute of Engineering and Technology Nanded India NVIDIA Santa Clara

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset. Copyright © 2018, The Authors. All rights reserved.

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Preface

Lecture Notes in Networks and Systems

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Lecture Notes in Networks and Systems 2023年 764 LNNS卷 v-vi页

作者： Milrad, Marcelo Otero, Nuno Sánchez-Gómez, María Cruz Mena, Juan José Durães, Dalila Sciarrone, Filippo Alvarez-Gómez, Claudio Rodrigues, Manuel Vittorini, Pierpaolo Gennari, Rosella Di Mascio, Tania Temperini, Marco De la Prieta, Fernando Linnaeus University Växjö Sweden University of Greenwich London United Kingdom Department of Didactics Organization and Research Method University of Salamanca Salamanca Spain University of Minho Braga Portugal Mercatorum University Rome Italy Facultad de Ingeniería y Ciencias Aplicadas Universidad de los Andes Santiago Chile Department of Life Health and Environmental Sciences University of L’Aquila L’Aquila Italy Faculty of Computer Science Free University of Bozen-Bolzano Bolzano Italy Department of Information Engineering Computer Science and Mathematics University of L’Aquila L’Aquila Italy Dipartimento di Ingegneria Informatica Sapienza Universita’ di Roma Rome Italy Department of Computer Science and Automation Control University of Salamanca Salamanca Spain

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Preconditioning for the integration of a spatiotemporal pharmacodynamic system

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PAMM 2023年第1期22卷

作者： Jurjen Duintjer Tebbens Martin Lanzendörfer Ctirad Matonoha Štěpán Papáček Department of Computational Mathematics Institute of Computer Science of the Czech Academy of Sciences Pod Vodárenskou věží 271/2 Praha - Libeň 182 07 Czech Republic Department of Biophysics and Physical Chemistry Faculty of Pharmacy in Hradec Kralove Charles University Heyrovského 1203 Hradec Králové 500 05 Czech Republic Department of Computational Mathematics Institute of Computer Science of the Czech Academy of Sciences Pod Vodárenskou věží 271/2 Praha - Libeň 182 07 Czech Republic Department of Biophysics and Physical Chemistry Faculty of Pharmacy in Hradec Kralove Charles University Heyrovského 1203 Hradec Králové 500 05 Czech Republic Institute of Hydrogeology Engineering Geology and Applied Geophysics Faculty of Science Charles University Albertov 6 128 43 Praha 2 Czech Republic Department of Control Theory Institute of Information Theory and Automation of the Czech Academy of Sciences Pod Vodárenskou věží 4 Praha - Libeň 182 00 Czech Republic

We address efficient modeling of the intracellular action of a drug binding to the nuclear pregnane X receptor. The binded complex enters the cell nucleus and acts on DNA, resulting in enhanced production of an enzyme which metabolizes, among others, co-administered drugs. Pharmacodynamic modeling is traditionally based on a compartmental approach, which simplifies the complex processes in the human body through the definition of a small number of compartments representing organs, tissues, cells, cytoplasm or abstract units. Inside a compartment, the concentrations of all substances are assumed to be distributed homogeneously, i.e. there is no spatial dependence. They lead to a system of ODEs for the time-dependence of the concentrations of the active substances. We will present an extension of a model from the literature for the action of the tuberculose-drug Rifampicin. The extension consists of a first attempt to add spatial resolution for substances that are active in the cytoplasm. Spatial resolution can be benecifial to analyze important issues like, among others, local exceeding of toxic drug levels, delay of transport and drug-drug interactions. We address efficient solution of the linear systems arising when numerically integrating the resulting PDE's and consider some preconditioning techniques based on properties of the underlying biochemical network.

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An evaluation of the instantaneous calculation of load current components

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European Transactions on Electrical Power 1993年第1期3卷 53-59页

作者： Marshall, D.A. Venter, F.P. van Wyk, J.D. Dr. Dirk Adriaan Marshall (1960) is an Industrial Research fellow with the Energy Laboratory at the Rand Afrikaans University Johannesburg/RSA. He is employed by Eskom (National Electric Company RSA) in the Transmission Engineering Division where his corporate responsibility includes high voltage direct current transmission and voltage quality. He obtained the 8. Eng. M. Eng. and D. Eng degrees in 1983 1985 and 1990 respectively from the Rand Afrikaans University. He was co-recipient of one IEEE Prize Paper Award. (Transmission Engineering Division Megawattpark P.O. Box 1091 Johannesburg 2000 Republic of South Africa T +2711/800-3250 Fax +27 11/800-2779) Frederik Petrus Venter (1966) received the B. Eng. and hit. Eng. degrees from the Rand Afrikaans University Johannesburg/RSA in 1989 and 1991 respectively. He has at present submitted a Thesis for the D. Eng. degree at the same University. His field of interest includes power electronic applications in high voltage networks and Active Power Filtering. He was co-recipient of one IEEE Prize Paper Award. (Rand Afrikaans University Laboratory for Energy P.O. Box 524 Johannesburg 2000. Republic of South Africa T + 2711/489-2454 Fax + 2711/489-2466) Dr. Jacobus Daniel Van Wyk (1939) received the M. Sc. Eng. degree from the University of Pretona/RSA and the degree of Doctorate of Technical Science from the University of Technology Eindhovenmhe Netherlands in 1966 and 1969. He has worked with the S.A. Iron and Steel Corporation. the University of Pretoria and was on the technical and scientific staff of the University in Eindhoven. between 1961 and 1972. From 1971 to the present he has been a Full Professor of Electrical and Electronic Engineering at the Rand Afrikaans University Johannesburg/RSA at present holding a chair in Power Electronics and has been involved in extensive industrial work. He is at present Programme Director of the Electronic Power Control Research Group in the Energy Laboratory of the Faculty of Engineering. Since 1976 he

The development of theoretical techniques for the instantaneous calculation of load current components is evaluated. The associated instantaneous calculation of load power components is also evaluated since it is used in the calculation of the currents. The generation of these different power components with respect to compensation are pointed out. Further implementation of the instantaneous power theory is discussed. A three‐phase vector approach to the instantaneous calculation of power components is also discussed. Experimental results obtained by using the instantaneous power theory are illustrated. Copyright © 1993 John Wiley & Sons, Ltd.

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XXIV World Allergy Congress 2015 Seoul, Korea. 14-17 October 2015 Abstracts

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WORLD ALLERGY ORGANIZATION JOURNAL 2016年第1期9卷 1-206页

作者： [Anonymous] Korea University College of Medicine Guro Hospital Seoul South Korea College of Medicine Korea University Seoul South Korea Korea University Guro Hospital Seoul South Korea Seoul National University Boramae Hospital Seoul South Korea Division of Clinical Immunology Faculty of Medicine University of Debrecen Debrecen Hungary Meiji Pharmaceutical University Tokyo Japan Suri Medical Foundation Hospital Uttar Pradesh State India Shahid Beheshti University Tehran Iran Airlangga University Teaching Hospital Surabaya Indonesia Tokyo Metropolitan Police Hospital Tokyo Japan Shinichiro KogaSamsung Changwon Hospital Seoul South Korea Sapporo Tokushukai Hospital Sapporo Japan Department of Dermatology Yonsei University College of Medicine Seoul South Korea Brain Korea 21 PLUS Project for Medical Science Yonsei University College of Medicine Seoul South Korea Sureyyapasa Chest Diseases and Chest Surgery Training Hospital Istanbul Turkey Kangnam Sacred Heart Hospital Seoul South Korea Sakai City Medical Center Sakai Japan Osaka University Suita Japan Yonsei University College of Medicine Seoul South Korea Osaka-Minami Medical Center Kawachinagano Japan Inha University College of Medicine Incheon South Korea Inha University Hospital Incheon South Korea Center for Rhinology and Allergology Wiesbaden Wiesbaden Germany Leti Pharma Gmbh Witten Germany Postgraduate Institute of Medical Education and Research Chandigarh India West Bengal Technical University Kolkata India Institute of Microbiology Academy of Sciences of the Czech Republic Prague Czech Republic Seoul National University Hospital Seoul South Korea Ent and Allergy Centre(INDIA) Panchkula India University of Santo Tomas Hospital Manila Philippines University of Santo Tomas Faculty of Medicine Manila Philippines Kyung Hee University Hospital at Gang-Dong Seoul South Korea Sangji University Wonju South Korea Division of Allergy and Immunology Department of Internal Medicine Yonsei University Colle

A1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblasts Jae-Min Shin, Heung-Man Lee, Il-Ho Park A2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistamines Hyun-Sun Yoon, Gyeong Yul Park A3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndrome Margit Zeher A4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cells Katsuhiko Matsui, Saki Tamai, Reiko Ikeda A5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintest Drsushil Suri, Dranu Suri A6 Evaluation ferqency of ADHD in childhood asthma Marzieh Heidarzadeh Arani A7 Steven johnson syndrome caused by typhoid fever in a child Azwin Lubis, Anang Endaryanto A8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 Asthma Shinichiro Koga A9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012) Lee Ju Suk A10 Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki A11 Subcutaneous immunotherapy mouse model for atopic dermatitis Seo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee A12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs? Fatma Merve Tepetam A13 Food hypersensitivity in patients with atopic dermatitis in Korea Chun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin Cho A14 Anaphylaxis caused by an ant (Brachyponera chinensis) in Japan Yoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi A

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Native diversity buffers against severity of non-native tree invasions ( vol 621,pg 773 , 2023 )

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NATURE 2023年第7982期622卷 E2-E2页

作者： Delavaux, Camille S. Crowther, Thomas W. Zohner, Constantin M. Robmann, Niamh M. Lauber, Thomas van den Hoogen, Johan Kuebbing, Sara Liang, Jingjing de-Miguel, Sergio Nabuurs, Gert-Jan Reich, Peter B. Abegg, Meinrad Yao, Yves C. Adou Alberti, Giorgio Zambrano, Angelica M. Almeyda Alvarado, Braulio Vilchez Alvarez-Davila, Esteban Alvarez-Loayza, Patricia Alves, Luciana F. Ammer, Christian Anton-Fernandez, Clara Araujo-Murakami, Alejandro Arroyo, Luzmila Avitabile, Valerio Aymard, Gerardo A. Baker, Timothy R. Balazy, Radomir Banki, Olaf Barroso, Jorcely G. Bastian, Meredith L. Bastin, Jean-Francois Birigazzi, Luca Birnbaum, Philippe Bitariho, Robert Boeckx, Pascal Bongers, Frans Bouriaud, Olivier Brancalion, Pedro H. S. Brandl, Susanne Brienen, Roel Broadbent, Eben N. Bruelheide, Helge Bussotti, Filippo Gatti, Roberto Cazzolla Cesar, Ricardo G. Cesljar, Goran Chazdon, Robin Chen, Han Y. H. Chisholm, Chelsea Cho, Hyunkook Cienciala, Emil Clark, Connie Clark, David Colletta, Gabriel D. Coomes, David A. Valverde, Fernando Cornejo Corral-Rivas, Jose J. Crim, Philip M. Cumming, Jonathan R. Dayanandan, Selvadurai de Gasper, Andre L. Decuyper, Mathieu Derroire, Geraldine DeVries, Ben Djordjevic, Ilija Dolezal, Jiri Dourdain, Aurelie Obiang, Nestor Laurier Engone Enquist, Brian J. Eyre, Teresa J. Fandohan, Adande Belarmain Fayle, Tom M. Feldpausch, Ted R. Ferreira, Leandro V. Fischer, Markus Fletcher, Christine Frizzera, Lorenzo Gamarra, Javier G. P. Gianelle, Damiano Glick, Henry B. Harris, David J. Hector, Andrew Hemp, Andreas Hengeveld, Geerten Herault, Bruno Herbohn, John L. Herold, Martin Hillers, Annika Coronado, Euridice N. Honorio Hui, Cang Ibanez, Thomas T. Amaral, Ieda Imai, Nobuo Jagodzinski, Andrzej M. Jaroszewicz, Bogdan Johannsen, Vivian Kvist Joly, Carlos A. Jucker, Tommaso Jung, Ilbin Karminov, Viktor Kartawinata, Kuswata Kearsley, Elizabeth Kenfack, David Kennard, Deborah K. Kepfer-Rojas, Sebastian Keppel, Gunnar Khan, Mohammed Latif Killeen, Timothy J. Kim, Hyun Seok Kitayama, Kanehiro Kohl, Michael Korju Institute of Integrative Biology ETH Zurich (Swiss Federal Institute of Technology) Zurich Switzerland Department of Genetics Evolution and Environment University College London London UK The Forest School at The Yale School of the Environment Yale University New Haven CT USA Department of Forestry and Natural Resources Purdue University West Lafayette IN USA Department of Agriculture Forestry and Bioresources Seoul National University Seoul South Korea Department of Crop and Forest Sciences University of Lleida Lleida Spain Joint Research Unit CTFC–AGROTECNIO–CERCA Solsona Spain Wageningen University and Research Wageningen The Netherlands World Agroforestry (ICRAF) Nairobi Kenya Department of Forest Resources University of Minnesota St Paul MN USA Hawkesbury Institute for the Environment Western Sydney University Penrith New South Wales Australia Institute for Global Change Biology and School for Environment and Sustainability University of Michigan Ann Arbor MI USA Swiss Federal Institute for Forest Snow and Landscape Research WSL Birmensdorf Switzerland UFR Biosciences University Félix Houphouët-Boigny Abidjan Côte d’Ivoire Department of Agricultural Food Environmental and Animal Sciences University of Udine Udine Italy Faculty of Science and Technology Free University of Bolzano Bolzano Italy Spatial Ecology and Conservation Laboratory Department of Tourism Recreation and Sport Management University of Florida Gainesville FL USA Forestry School Tecnológico de Costa Rica TEC Cartago Costa Rica Fundacion ConVida Universidad Nacional Abierta y a Distancia UNAD Medellin Colombia Field Museum of Natural Histiory Chicago IL USA Center for Tropical Research Institute of the Environment and Sustainability UCLA Los Angeles CA USA Silviculture and Forest Ecology of the Temperate Zones University of Göttingen Göttingen Germany Division of Forest and Forest Resources Norwegian Institute of Bioeconomy Research (NIBIO) Ås Norway Museo de Hi

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Author Correction: A consensus protocol for functional connectivity analysis in the rat brain

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Nature neuroscience 2023年 2023 Apr 18页

作者： Joanes Grandjean Gabriel Desrosiers-Gregoire Cynthia Anckaerts Diego Angeles-Valdez Fadi Ayad David A Barrière Ines Blockx Aleksandra Bortel Margaret Broadwater Beatriz M Cardoso Marina Célestine Jorge E Chavez-Negrete Sangcheon Choi Emma Christiaen Perrin Clavijo Luis Colon-Perez Samuel Cramer Tolomeo Daniele Elaine Dempsey Yujian Diao Arno Doelemeyer David Dopfel Lenka Dvořáková Claudia Falfán-Melgoza Francisca F Fernandes Caitlin F Fowler Antonio Fuentes-Ibañez Clément M Garin Eveline Gelderman Carla E M Golden Chao C G Guo Marloes J A G Henckens Lauren A Hennessy Peter Herman Nita Hofwijks Corey Horien Tudor M Ionescu Jolyon Jones Johannes Kaesser Eugene Kim Henriette Lambers Alberto Lazari Sung-Ho Lee Amanda Lillywhite Yikang Liu Yanyan Y Liu Alejandra López-Castro Xavier López-Gil Zilu Ma Eilidh MacNicol Dan Madularu Francesca Mandino Sabina Marciano Matthew J McAuslan Patrick McCunn Alison McIntosh Xianzong Meng Lisa Meyer-Baese Stephan Missault Federico Moro Daphne M P Naessens Laura J Nava-Gomez Hiroi Nonaka Juan J Ortiz Jaakko Paasonen Lore M Peeters Mickaël Pereira Pablo D Perez Marjory Pompilus Malcolm Prior Rustam Rakhmatullin Henning M Reimann Jonathan Reinwald Rodrigo Triana Del Rio Alejandro Rivera-Olvera Daniel Ruiz-Pérez Gabriele Russo Tobias J Rutten Rie Ryoke Markus Sack Piergiorgio Salvan Basavaraju G Sanganahalli Aileen Schroeter Bhedita J Seewoo Erwan Selingue Aline Seuwen Bowen Shi Nikoloz Sirmpilatze Joanna A B Smith Corrie Smith Filip Sobczak Petteri J Stenroos Milou Straathof Sandra Strobelt Akira Sumiyoshi Kengo Takahashi Maria E Torres-García Raul Tudela Monica van den Berg Kajo van der Marel Aran T B van Hout Roberta Vertullo Benjamin Vidal Roël M Vrooman Victora X Wang Isabel Wank David J G Watson Ting Yin Yongzhi Zhang Stefan Zurbruegg Sophie Achard Sarael Alcauter Dorothee P Auer Emmanuel L Barbier Jürgen Baudewig Christian F Beckmann Nicolau Beckmann Guillaume J P C Becq Erwin L A Blezer Radu Bolbos Susann Boretius Sandrine Bouvard Eike Budinger Joseph D Buxbaum Diana Cash Victor Donders Institute for Brain Behaviour and Cognition Radboud University Nijmegen The Netherlands. joanes.grandjean@radboudumc.nl. Department for Medical Imaging Radboud University Medical Center Nijmegen The Netherlands. joanes.grandjean@radboudumc.nl. Cerebral Imaging Centre Douglas Mental Health University Institute Verdun QC Canada. Integrated Program in Neuroscience McGill University Montreal QC Canada. Bio-imaging Lab University of Antwerp Antwerp Belgium. µNEURO Research Centre of Excellence University of Antwerp Antwerp Belgium. Instituto de Neurobiología Universidad Nacional Autónoma de México Campus Juriquilla Querétaro Mexico. Biological and Biomedical Engineering McGill University Montreal QC Canada. McConnell Brain Imaging Centre McGill University Montreal QC Canada. Montreal Neurological Institute McGill University Montreal QC Canada. UMR INRAE/CNRS 7247 Physiologie des Comportements et de la Reproduction Physiologie de la reproduction et des comportements Centre de recherche INRAE de Nouzilly Tours France. Department of Neurology and Neurosurgery McGill University Montreal QC Canada. Center for Animal MRI University of North Carolina at Chapel Hill Chapel Hill NC USA. Department of Neurology University of North Carolina at Chapel Hill Chapel Hill NC USA. Biomedical Research Imaging Center University of North Carolina at Chapel Hill Chapel Hill NC USA. Preclinical MRI Champalimaud Research Champalimaud Centre for the Unknown Lisbon Portugal. Laboratoire des Maladies Neurodégénératives Molecular Imaging Research Center (MIRCen) Université Paris-Saclay Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) CNRS Fontenay-aux-Roses France. Departamento de Neurobiología Conductual y Cognitiva Instituto de Neurobiología Universidad Nacional Autónoma de México Campus Juriquilla Querétaro México. Translational Neuroimaging and Neural Control Group High-Field Magnetic Resonance Max Planck Institute for Biological Cyberneti

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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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Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

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Scientific data 2017年第1期4卷 170179页

作者： Jason Flannick Christian Fuchsberger Anubha Mahajan Tanya M Teslovich Vineeta Agarwala Kyle J Gaulton Lizz Caulkins Ryan Koesterer Clement Ma Loukas Moutsianas Davis J McCarthy Manuel A Rivas John R B Perry Xueling Sim Thomas W Blackwell Neil R Robertson N William Rayner Pablo Cingolani Adam E Locke Juan Fernandez Tajes Heather M Highland Josee Dupuis Peter S Chines Cecilia M Lindgren Christopher Hartl Anne U Jackson Han Chen Jeroen R Huyghe Martijn van de Bunt Richard D Pearson Ashish Kumar Martina Müller-Nurasyid Niels Grarup Heather M Stringham Eric R Gamazon Jaehoon Lee Yuhui Chen Robert A Scott Jennifer E Below Peng Chen Jinyan Huang Min Jin Go Michael L Stitzel Dorota Pasko Stephen C J Parker Tibor V Varga Todd Green Nicola L Beer Aaron G Day-Williams Teresa Ferreira Tasha Fingerlin Momoko Horikoshi Cheng Hu Iksoo Huh Mohammad Kamran Ikram Bong-Jo Kim Yongkang Kim Young Jin Kim Min-Seok Kwon Juyoung Lee Selyeong Lee Keng-Han Lin Taylor J Maxwell Yoshihiko Nagai Xu Wang Ryan P Welch Joon Yoon Weihua Zhang Nir Barzilai Benjamin F Voight Bok-Ghee Han Christopher P Jenkinson Teemu Kuulasmaa Johanna Kuusisto Alisa Manning Maggie C Y Ng Nicholette D Palmer Beverley Balkau Alena Stančáková Hanna E Abboud Heiner Boeing Vilmantas Giedraitis Dorairaj Prabhakaran Omri Gottesman James Scott Jason Carey Phoenix Kwan George Grant Joshua D Smith Benjamin M Neale Shaun Purcell Adam S Butterworth Joanna M M Howson Heung Man Lee Yingchang Lu Soo-Heon Kwak Wei Zhao John Danesh Vincent K L Lam Kyong Soo Park Danish Saleheen Wing Yee So Claudia H T Tam Uzma Afzal David Aguilar Rector Arya Tin Aung Edmund Chan Carmen Navarro Ching-Yu Cheng Domenico Palli Adolfo Correa Joanne E Curran Dennis Rybin Vidya S Farook Sharon P Fowler Barry I Freedman Michael Griswold Daniel Esten Hale Pamela J Hicks Chiea-Chuen Khor Satish Kumar Benjamin Lehne Dorothée Thuillier Wei Yen Lim Jianjun Liu Marie Loh Solomon K Musani Sobha Puppala William R Scott Loïc Yengo Sian-Tsung Tan Herman A Taylor Farook Thameem Gregory Wilson Tien Yin Wong Pål Rasmu Department of Molecular Biology Massachusetts General Hospital Boston Massachusetts USA. Program in Medical and Population Genetics Broad Institute Cambridge Massachusetts USA. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor Michigan USA. Wellcome Trust Centre for Human Genetics Nuffield Department of Medicine University of Oxford Oxford UK. Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge Massachusetts USA. Department of Statistics University of Oxford Oxford UK. Genetics of Complex Traits University of Exeter Medical School University of Exeter Exeter UK. MRC Epidemiology Unit Institute of Metabolic Science University of Cambridge Cambridge UK. Department of Twin Research and Genetic Epidemiology King's College London London UK. Oxford Centre for Diabetes Endocrinology and Metabolism Radcliffe Department of Medicine University of Oxford Oxford UK. Department of Human Genetics Wellcome Trust Sanger Institute Hinxton Cambridgeshire UK. School of Computer Science McGill University Montreal Quebec Canada. McGill University and Génome Québec Innovation Centre Montreal Quebec Canada. Human Genetics Center The University of Texas Graduate School of Biomedical Sciences at Houston The University of Texas Health Science Center at Houston Houston Texas USA. Department of Biostatistics Boston University School of Public Health Boston Massachusetts USA. National Heart Lung and Blood Institute's Framingham Heart Study Framingham Massachusetts USA. Medical Genomics and Metabolic Genetics Branch National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA. Department of Biostatistics Harvard School of Public Health Boston Massachusetts USA. Chronic Disease Epidemiology Swiss Tropical and Public Health Institute University of Basel Basel Switzerland. Institute of Genetic Epidemiology Helmholtz Zentrum München German R

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

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