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BFGTP: A BERT-Guided Two-Stage Molecular Representation Learning Framework for Toxicity Prediction

IEEE Journal of Biomedical and Health informatics 2025年 PP卷 PP页

作者： Hu, Kaimiao He, Yuan Wei, Jianguo Sun, Changming Geng, Jie Wei, Leyi Su, Ran Tianjin University College of Intelligence and Computing Tianjin30000 China CSIRO Data61 SydneyNSW1710 Australia Tianjin University Tianjin Key Laboratory of Cardiovascular Emergency and Critical Care Tianjin Municipal Science and Technology Bureau Department of Cardiology Chest Hospital Tianjin China Macao Polytechnic University Centre for Artificial Intelligence driven Drug Discovery Faculty of Applied Science China Xiamen University School of Informatics Xiamen China

Accurate prediction of molecular toxicity is vital for drug development. Most mainstream methods rely on fingerprints or graph-based feature extraction, the emergence of large language models (LLMs) offers new prospects for molecular representation learning in toxicity prediction. Although several studies attempt to leverage LLMs to integrate molecular sequence data for pretraining molecular representations, certain limitations remain. Current LLM-based approaches usually utilize solely on class embedding features, overlooking the rich information in sequence embedding. Moreover, integrating pre-trained molecular representations with multi-modal molecular data may further enhance performance in toxicity prediction. To address these challenges, we propose BFGTP, a BERT-guided two-stage molecular representation learning framework for toxicity prediction. Firstly, we design independent encoders for molecular descriptions of three modalities, where the fingerprint encoder with dual level attention mechanisms effectively integrates multi-category fingerprints. Then, the two-stage guide strategy is introduced to fully utilize the prior knowledge of LLMs, employing contrastive learning to align and fuse the tri-modal representations and knowledge distillation to align predicted value distributions. BFGTP ultimately combines fingerprint and graph representations to predict molecular toxicity. Experiments on seven toxicity datasets show that BFGTP outperforms baselines, achieving the highest AUC on five datasets and the best average performance across five evaluation metrics. Ablation studies, t-SNE visualization and case study confirm the effectiveness of BFGTP's components and its ability to capture meaningful molecular representations. ©2013 IEEE.

关键词： Contrastive Learning

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Strategic priorities for transformative progress in advancing biology with proteomics and artificial intelligence

arXiv

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arXiv 2025年

作者： Sun, Yingying Jun, A. Liu, Zhiwei Sun, Rui Qian, Liujia Payne, Samuel H. Bittremieux, Wout Ralser, Markus Li, Chen Chen, Yi Dong, Zhen Perez-Riverol, Yasset Khan, Asif Sander, Chris Aebersold, Ruedi Vizcaíno, Juan Antonio Krieger, Jonathan R. Yao, Jianhua Wen, Han Zhang, Linfeng Zhu, Yunping Xuan, Yue Sun, Benjamin Boyang Qiao, Liang Hermjakob, Henning Tang, Haixu Gao, Huanhuan Deng, Yamin Zhong, Qing Chang, Cheng Bandeira, Nuno Li, Ming Weinan, E. Sun, Siqi Yang, Yuedong Omenn, Gilbert S. Zhang, Yue Xu, Ping Fu, Yan Liu, Xiaowen Overall, Christopher M. Wang, Yu Deutsch, Eric W. Chen, Luonan Cox, Jürgen Demichev, Vadim He, Fuchu Huang, Jiaxing Jin, Huilin Liu, Chao Li, Nan Luan, Zhongzhi Song, Jiangning Yu, Kaicheng Wan, Wanggen Wang, Tai Zhang, Kang Zhang, Le Bell, Peter A. Mann, Matthias Zhang, Bing Guo, Tiannan Affiliated Hangzhou First People’s Hospital State Key Laboratory of Medical Proteomics School of Medicine Westlake University Zhejiang Province Hangzhou China Westlake Center for Intelligent Proteomics Westlake Laboratory of Life Sciences and Biomedicine Zhejiang Province Hangzhou China Biology Department Brigham Young University ProvoUT84602 United States Department of Computer Science University of Antwerp Antwerp2020 Belgium Department of Biochemistry CharitéUniversitätsmedizin Berlin Berlin Germany Biomedicine Discovery Institute Department of Biochemistry and Molecular Biology Monash University MelbourneVICVIC 3800 Australia Wellcome Genome Campus Hinxton CambridgeCB10 1SD United Kingdom Harvard Medical School Ludwig Center at Harvard United States Harvard Medical School Broad Institute Ludwig Center at Harvard Dana-Farber Cancer Institute United States Department of Biology Institute of Molecular Systems Biology ETH Zürich Zürich Switzerland Bruker Ltd. MiltonONL9T 6P4 Canada AI for Life Sciences Lab Tencent Shenzhen518057 China State Key Laboratory of Medical Proteomics AI for Science Institute Beijing100080 China Beijing Institute of Lifeomics Beijing102206 China Thermo Fisher Scientific GmbH Hanna-Kunath Str. 11 Bremen28199 Germany Informatics and Predictive Sciences Research Bristol Myers Squibb United States Department of Chemistry Fudan University Songhu Road 2005 Shanghai200438 China Department of Computer Science Luddy School of Informatics Computing and Engineering Indiana University IN47408 United States ProCan® Children’s Medical Research Institute Faculty of Medicine and Health The University of Sydney WestmeadNSW Australia La Jolla CA United States Central China Institute of Artificial Intelligence University of Waterloo Canada AI for Science Institute Center for Machine Learning Research School of Mathematical Sciences Peking University China Research Institute of Intelligent Complex Systems Fudan U

Artificial intelligence (AI) is transforming scientific research, including proteomics. Advances in mass spectrometry (MS)-based proteomics data quality, diversity, and scale, combined with groundbreaking AI techniques, are unlocking new challenges and opportunities in biological discovery. Here, we highlight key areas where AI is driving innovation, from data analysis to new biological insights. These include developing an AI-friendly ecosystem for proteomics data generation, sharing, and analysis;improving peptide and protein identification and quantification;characterizing protein-protein interactions and protein complexes;advancing spatial and perturbation proteomics;integrating multi-omics data;and ultimately enabling AI-empowered virtual cells. © 2025, CC BY.

关键词： Biotic

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Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease

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Computers in Biology and Medicine 2024年 176卷 108588-108588页

作者： Gómez-Pascual, Alicia Naccache, Talel Xu, Jin Hooshmand, Kourosh Wretlind, Asger Gabrielli, Martina Lombardo, Marta Tiffany Shi, Liu Buckley, Noel J. Tijms, Betty M. Vos, Stephanie J.B. ten Kate, Mara Engelborghs, Sebastiaan Sleegers, Kristel Frisoni, Giovanni B. Wallin, Anders Lleó, Alberto Popp, Julius Martinez-Lage, Pablo Streffer, Johannes Barkhof, Frederik Zetterberg, Henrik Visser, Pieter Jelle Lovestone, Simon Bertram, Lars Nevado-Holgado, Alejo J. Gualerzi, Alice Picciolini, Silvia Proitsi, Petroula Verderio, Claudia Botía, Juan A. Legido-Quigley, Cristina Department of Information and Communications Engineering Faculty of Informatics University of Murcia Murcia Spain Steno Diabetes Center Copenhagen Herlev Denmark Department of Data Science City University of London United Kingdom Institute of Pharmaceutical Science King's College London London United Kingdom CNR Institute of Neuroscience Vedano al Lambro20854 Italy School of Medicine and Surgery University of Milano-Bicocca 20126 Italy Oxford United Kingdom Department of Psychiatry University of Oxford United Kingdom Kavli Institute for Nanoscience Discovery Denmark Alzheimer Center VU University Medical Center Amsterdam Netherlands Department of Psychiatry and Neuropsychology Alzheimer Centrum Limburg Maastricht University Maastricht Netherlands Department of Biomedical Sciences University of Antwerp Antwerp Belgium Vrije Universiteit Brussel Brussels Belgium Complex Genetics Group VIB Center for Molecular Neurology VIB Antwerp Belgium Institute Born-Bunge Department of Biomedical Sciences University of Antwerp Antwerp Belgium University of Geneva Geneva Switzerland IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli Brescia Italy Institute of Neuroscience and Physiology Sahlgrenska Academy at University of Gothenburg Gothenburg Sweden Barcelona Spain Old age psychiatry University Hospital of Lausanne University of Lausanne Switzerland Department of Geriatric Psychiatry University Hospital of Psychiatry Zürich University of Zürich Switzerland CITA-Alzheimer Foundation San Sebastian Spain AC Immune SA formerly Janssen R&D LLC. Beerse Belgium at the time of study conduct Lausanne Switzerland Department of Radiology and Nuclear Medicine Amsterdam UMC Vrije Universiteit Netherlands Queen Square Institute of Neurology and Centre for Medical Image Computing University College London United Kingdom Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden Department of Psychiatry and Neurochemistry Institute of

Background: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Method: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Results: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. Conclusions: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways. © 2024 The Authors

关键词： Metabolites

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BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets

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Nature methods 2023年第6期20卷 824-835页

作者： Linus Manubens-Gil Zhi Zhou Hanbo Chen Arvind Ramanathan Xiaoxiao Liu Yufeng Liu Alessandro Bria Todd Gillette Zongcai Ruan Jian Yang Miroslav Radojević Ting Zhao Li Cheng Lei Qu Siqi Liu Kristofer E Bouchard Lin Gu Weidong Cai Shuiwang Ji Badrinath Roysam Ching-Wei Wang Hongchuan Yu Amos Sironi Daniel Maxim Iascone Jie Zhou Erhan Bas Eduardo Conde-Sousa Paulo Aguiar Xiang Li Yujie Li Sumit Nanda Yuan Wang Leila Muresan Pascal Fua Bing Ye Hai-Yan He Jochen F Staiger Manuel Peter Daniel N Cox Michel Simonneau Marcel Oberlaender Gregory Jefferis Kei Ito Paloma Gonzalez-Bellido Jinhyun Kim Edwin Rubel Hollis T Cline Hongkui Zeng Aljoscha Nern Ann-Shyn Chiang Jianhua Yao Jane Roskams Rick Livesey Janine Stevens Tianming Liu Chinh Dang Yike Guo Ning Zhong Georgia Tourassi Sean Hill Michael Hawrylycz Christof Koch Erik Meijering Giorgio A Ascoli Hanchuan Peng Institute for Brain and Intelligence Southeast University Nanjing China. Microsoft Corporation Redmond WA USA. Tencent AI Lab Bellevue WA USA. Computing Environment and Life Sciences Directorate Argonne National Laboratory Lemont IL USA. Kaya Medical Seattle WA USA. University of Cassino and Southern Lazio Cassino Italy. Center for Neural Informatics Structures and Plasticity Krasnow Institute for Advanced Study George Mason University Fairfax VA USA. Faculty of Information Technology Beijing University of Technology Beijing China. Beijing International Collaboration Base on Brain Informatics and Wisdom Services Beijing China. Nuctech Netherlands Rotterdam the Netherlands. Janelia Research Campus Howard Hughes Medical Institute Ashburn VA USA. Department of Electrical and Computer Engineering University of Alberta Edmonton Alberta Canada. Ministry of Education Key Laboratory of Intelligent Computation and Signal Processing Anhui University Hefei China. Paige AI New York NY USA. Scientific Data Division and Biological Systems and Engineering Division Lawrence Berkeley National Lab Berkeley CA USA. Helen Wills Neuroscience Institute and Redwood Center for Theoretical Neuroscience UC Berkeley Berkeley CA USA. RIKEN AIP Tokyo Japan. Research Center for Advanced Science and Technology (RCAST) The University of Tokyo Tokyo Japan. School of Computer Science University of Sydney Sydney New South Wales Australia. Texas A&M University College Station TX USA. Cullen College of Engineering University of Houston Houston TX USA. Graduate Institute of Biomedical Engineering National Taiwan University of Science and Technology Taipei Taiwan. National Centre for Computer Animation Bournemouth University Poole UK. PROPHESEE Paris France. Department of Neuroscience Columbia University New York NY USA. Mortimer B. Zuckerman Mind Brain Behavior Institute Columbia University New York NY USA. Department of Computer Science Northern Illinois Universit

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.

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

arXiv

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arXiv 2025年

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

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

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Author Correction: BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets

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Nature methods 2024年第10期21卷 1959页

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Aligning the human phenotype and mammalian phenotype ontology using dead simple ontology design patterns 8

Aligning the human phenotype and mammalian phenotype ontolog...

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8th International Conference on Biomedical Ontology, ICBO 2017

作者： Vasilevsky, Nicole Balhoff, James P. Mungall, Christopher J. Osumi-Sutherland, David Kohler, Sebastian Bello, Susan Smith, Cynthia Robinson, Peter Haendel, Melissa Ontology Development Group OHSU Library Oregon Health and Science University 3181 SW Sam Jackson Park Road PortlandOR United States Renaissance Computing Institute University of North Carolina 100 Europa Drive Suite 540 Chapel HillNC United States Environmental Genomics and Systems Biology Lawrence Berkeley National Laboratory 1 Cyclotron Road MS977 BerkeleyCA United States School of Informatics University of Edinburgh 10 Crichton Street Edinburgh Scotland United Kingdom Charité - Universitätsmedizin Berlin Berlin10117 Germany The Jackson Laboratory 600 Main St Bar HarborME United States The Jackson Laboratory for Genomic Medicine 10 Discovery Drive FarmingtonCT United States

The Human Phenotype Ontology (HP) and Mammalian Phenotype (MP) Ontology represent information about abnormal phenotypes encountered in human diseases and mammalian organisms, respectively. It is a goal to co-develop these ontologies and align the terminology and logical axioms to increase interoperability of the two ontologies. Towards this end, we have worked to develop consistent design patterns for commonly used types of classes, such as morphological phenotypes or abnormal anatomical structures. We are currently implementing ‘dead simple ontology design patterns’ (DOSDP), which are design patterns that can be specified in a YAML text file and can be used to generate new terms, documentation, retrofit old terms, and allows for reuse of patterns. This paper describes the development and implementation of the DOSDP in the HP and MP. © 2018 CEUR-WS. All rights reserved.

关键词： Ontology

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Big Data Research in Italy： A Perspective

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Engineering 2016年第2期2卷 163-170页

作者： Sonia Bergamaschi Emanuele Carlini Michelangelo Ceci Barbara Furletti Fosca Giannotti Donato Malerba Mario Mezzanzanica Anna Monreale Gabriella Pasi Dino Pedreschi Raffele Perego Salvatore Ruggieri Department of Engneering "Enzo Ferrari " University of Modena and Reggio Emilia Modena 41125 Italy High Performance Computing Laboratory Institute of Information Science and Technologies of the Italian National Research Council (ISTI-CNR) Pisa 56124 Italy Department of Computer Science University ofBari Aldo Moro Bari 70125 Italy Knowledge Discovery and Data Mining Laboratory ISTI-CNR Pisa 56127 Italy Big Data Laboratory National Interuniversity Consortium for Informatics Rome 00185 Italy Department of Statistics and Quantitative Methods University of Milano-Bicocca Milan 20126 Italy Department of Computer Science Systems and Communications University of Milano-Bicocca Milan 20126 Italy Department of Computer 5denee University of Pisa Pisa 56127 Italy

The aim of this article is to synthetically describe the research projects that a selection of Italian univer- sities is undertaking in the context of big data. Far from being exhaustive, this article has the objective of offering a sample of distinct applications that address the issue of managing huge amounts of data in Italy, collected in relation to diverse domains.

关键词： Big data Smart cities EnergyJob offersPrivacy

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Author Correction: The challenge of mapping the human connectome based on diffusion tractography

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Nature communications 2019年第1期10卷 5059页

作者： Klaus H Maier-Hein Peter F Neher Jean-Christophe Houde Marc-Alexandre Côté Eleftherios Garyfallidis Jidan Zhong Maxime Chamberland Fang-Cheng Yeh Ying-Chia Lin Qing Ji Wilburn E Reddick John O Glass David Qixiang Chen Yuanjing Feng Chengfeng Gao Ye Wu Jieyan Ma Renjie He Qiang Li Carl-Fredrik Westin Samuel Deslauriers-Gauthier J Omar Ocegueda González Michael Paquette Samuel St-Jean Gabriel Girard François Rheault Jasmeen Sidhu Chantal M W Tax Fenghua Guo Hamed Y Mesri Szabolcs Dávid Martijn Froeling Anneriet M Heemskerk Alexander Leemans Arnaud Boré Basile Pinsard Christophe Bedetti Matthieu Desrosiers Simona Brambati Julien Doyon Alessia Sarica Roberta Vasta Antonio Cerasa Aldo Quattrone Jason Yeatman Ali R Khan Wes Hodges Simon Alexander David Romascano Muhamed Barakovic Anna Auría Oscar Esteban Alia Lemkaddem Jean-Philippe Thiran H Ertan Cetingul Benjamin L Odry Boris Mailhe Mariappan S Nadar Fabrizio Pizzagalli Gautam Prasad Julio E Villalon-Reina Justin Galvis Paul M Thompson Francisco De Santiago Requejo Pedro Luque Laguna Luis Miguel Lacerda Rachel Barrett Flavio Dell'Acqua Marco Catani Laurent Petit Emmanuel Caruyer Alessandro Daducci Tim B Dyrby Tim Holland-Letz Claus C Hilgetag Bram Stieltjes Maxime Descoteaux Division of Medical Image Computing German Cancer Research Center (DKFZ) Heidelberg 69120 Germany. k.maier-hein@dkfz.de. Division of Medical Image Computing German Cancer Research Center (DKFZ) Heidelberg 69120 Germany. Sherbrooke Connectivity Imaging Lab (SCIL) Université de Sherbrooke Sherbrooke QC J1K 0A5 QC Canada. Department of Intelligent Systems Engineering School of Informatics and Computing Indiana University Bloomington IN 47408 USA. Krembil Research Institute University Health Network Toronto Canada M5G 2C4. Department of Neurological Surgery University of Pittsburgh School of Medicine Pittsburgh PA 15213 USA. IMT-Institute for Advanced Studies Lucca 55100 Italy. Department of Diagnostic Imaging St. Jude Children's Research Hospital Memphis TN 38105 USA. University of Toronto Institute of Medical Science Toronto Canada M5S 1A8. Institute of Information Processing and Automation Zhejiang University of Technology Hangzhou 310023 Zhejiang China. United Imaging Healthcare Co Shanghai 201807 China. Shanghai Advanced Research Institute Shanghai 201210 China. Laboratory of Mathematics in Imaging Harvard Medical School Boston MA 02215 USA. Center for Research in Mathematics Guanajuato 36023 Mexico. PROVIDI Lab Image Sciences Institute University Medical Center Utrecht Utrecht 3508 The Netherlands. Cardiff University Brain Research Imaging Centre School of Psychology Cardiff University Maindy Road Cardiff CF24 4HQ UK. Department of Radiology University Medical Center Utrecht Utrecht 3508 The Netherlands. Centre de recherche institut universitaire de geriatrie de Montreal (CRIUGM) Université de Montréal Montreal QC Canada H3W 1W5. Sorbonne Universités UPMC Univ Paris 06 CNRS INSERM Laboratoire d'Imagerie Biomédicale (LIB) 75013 Paris France. Center for Advanced Research in Sleep Medicine Hôpital du Sacré-Coeur de Montréal Montreal Canada H4J 1C5. Neuroimaging Unit Institute of Bioimaging and Molecular Physiology (IBFM) Nat

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

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NATURE GENETICS 2018年第12期50卷 1755-1755页

作者： Evangelou, Evangelos Warren, Helen R. Mosen-Ansorena, David Mifsud, Borbala Pazoki, Raha Gao, He Ntritsos, Georgios Dimou, Niki Cabrera, Claudia P. Karaman, Ibrahim Fu Liang Ng Evangelou, Marina Witkowska, Katarzyna Tzanis, Evan Hellwege, Jacklyn N. Giri, Ayush Edwards, Digna R. Velez Sun, Yan V. Cho, Kelly Gaziano, J. Michael Wilson, Peter W. F. Tsao, Philip S. Kovesdy, Csaba P. Esko, Tonu Magi, Reedik Milani, Lili Almgren, Peter Boutin, Thibaud Debette, Stephanie Ding, Jun Giulianini, Franco Holliday, Elizabeth G. Jackson, Anne U. Li-Gao, Ruifang Lin, Wei-Yu Luan, Jian'an Mangino, Massimo Oldmeadow, Christopher Prins, Bram Peter Qian, Yong Sargurupremraj, Muralidharan Shah, Nabi Surendran, Praveen Theriault, Sebastien Verweij, Niek Willems, Sara M. Zhao, Jing-Hua Amouyel, Philippe Connell, John de Mutsert, Renee Doney, Alex S. F. Farrall, Martin Menni, Cristina Morris, Andrew D. Noordam, Raymond Pare, Guillaume Poulter, Neil R. Shields, Denis C. Stanton, Alice Thom, Simon Abecasis, Goncalo Amin, Najaf Arking, Dan E. Ayers, Kristin L. Barbieri, Caterina M. Batini, Chiara Bis, Joshua C. Blake, Tineka Bochud, Murielle Boehnke, Michael Boerwinkle, Eric Boomsma, Dorret I. Bottinger, Erwin P. Braund, Peter S. Brumat, Marco Campbell, Archie Campbell, Harry Chakravarti, Aravinda Chambers, John C. Chauhan, Ganesh Ciullo, Marina Cocca, Massimiliano Collins, Francis Cordell, Heather J. Davies, Gail de Borst, Martin H. de Geus, Eco J. Deary, Ian J. Deelen, Joris Del Greco, Fabiola M. Demirkale, Cumhur Yusuf Dorr, Marcus Ehret, Georg B. Elosua, Roberto Enroth, Stefan Erzurumluoglu, A. Mesut Ferreira, Teresa Franberg, Mattias Franco, Oscar H. Gandin, Ilaria Gasparini, Paolo Giedraitis, Vilmantas Gieger, Christian Girotto, Giorgia Goel, Anuj Gow, Alan J. Gudnason, Vilmundur Guo, Xiuqing Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Harris, Sarah E. Hartman, Catharina A. Havulinna, Aki S. Hicks, Andrew A. Hofer, Edith Hofman, Albert Hottenga, Jouke-Jan Huffman, Jennifer E. Hwang, Shih-Jen Ingelsson, Erik James, Alan Jansen Department of Epidemiology and Biostatistics Imperial College London London UK. Department of Hygiene and Epidemiology University of Ioannina Medical School Ioannina Greece. William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK. National Institute for Health Research Barts Cardiovascular Biomedical Research Center Queen Mary University of London London UK. MRC-PHE Centre for Environment and Health Imperial College London London UK. Department of Mathematics Imperial College London London UK. Division of Epidemiology Department of Medicine Institute for Medicine and Public Health Vanderbilt Genetics Institute Vanderbilt University Medical Center Tennessee Valley Healthcare System (626)/Vanderbilt University Nashville TN USA. Vanderbilt Genetics Institute Vanderbilt Epidemiology Center Department of Obstetrics and Gynecology Vanderbilt University Medical Center Tennessee Valley Health Systems VA Nashville TN USA. Department of Epidemiology Emory University Rollins School of Public Health Atlanta GA USA. Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) VA Boston Healthcare System Boston MA USA. Division of Aging Department of Medicine Brigham and Women's Hospital Department of Medicine Harvard Medical School Boston MA USA. Atlanta VAMC and Emory Clinical Cardiovascular Research Institute Atlanta GA USA. VA Palo Alto Health Care System Division of Cardiovascular Medicine Stanford University School of Medicine Stanford CA USA. Nephrology Section Memphis VA Medical Center and University of Tennessee Health Science Center Memphis TN USA. Estonian Genome Center University of Tartu Tartu Estonia. Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Department Clinical Sciences Malmö Lund University Malmö Sweden. MRC

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

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