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3rd International Conference on Computing and Applied informatics 2018, ICCAI 2018

作者： Syahputra, M.F. Angkasih, A.P. Purnamawati, S. Andayani, U. Abdullah, D. Sriadhi, S. Iskandar, A. Rosida, T.M. Fitriany, J. Sari, I.N. Utama, M.D. Nanuru, R.F. Department of Information Technology Faculty of Computer Science and Information Technology Universitas Sumatera Utara Medan Indonesia Department of Informatics Universitas Malikussaleh Aceh Utara Indonesia Department of Electrical Engineering Universitas Negeri Medan Indonesia Informatics Engineering STMIK AKBA Makassar Indonesia Graduate Program in Scientific Psychology Universitas Kristen Maranatha Indonesia Department of Pediatric Universitas Malikussaleh Aceh Utara Indonesia Departement of Social Science Education Program Post Graduate Program Universitas Kanjuruhan Malang Malang Indonesia Faculty of Social and Political Science Universitas Kristen Indonesia Maluku Indonesia Universitas Kristen Indonesia Maluku Ambon Indonesia

Autism Spectrum Disorder is a pervasive developmental disorder that will affect children in terms of interpersonal communication, social interaction, and imaginative levels in play. Many therapies to help the motor neuron performance is one of them Pretend Play. Pretend Play is a therapy that invites children in playing to demonstrate something else and tell how to use objects that are considered in the child's imagination. However, in the era of highly developed technology, many fields have used the Augmented Reality method as a visualization of various aspects. With this method researchers will present the therapeutic visualization of the block to 3D transportation tool that is useful for strengthening motor nerves and visual strength of the child. The system can run well during marker detection, marker movement, and 3D object display with the accuracy of precision angle and distance between virtual world with real world reach 100% with angle 0 at distance 31 cm and the maximum distance from the marker is 46 cm and the maximum angle is 30. © 2019 Published under licence by IOP Publishing Ltd.

关键词： Augmented reality

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Ontologizing Health Systems Data at Scale: Making Translational Discovery a Reality

arXiv

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arXiv 2022年

作者： Callahan, Tiffany J. Stefanski, Adrianne L. Wyrwa, Jordan M. Zeng, Chenjie Ostropolets, Anna Banda, Juan M. Baumgartner, William A. Boyce, Richard D. Casiraghi, Elena Coleman, Ben D. Collins, Janine H. Deakyne-Davies, Sara J. Feinstein, James A. Haendel, Melissa A. Lin, Asiyah Y. Martin, Blake Matentzoglu, Nicolas A. Meeker, Daniella Reese, Justin Sinclair, Jessica Taneja, Sanya B. Trinkley, Katy E. Vasilevsky, Nicole A. Williams, Andrew Zhang, Xingman A. Denny, Joshua C. Robinson, Peter N. Ryan, Patrick Hripcsak, George Bennett, Tellen D. Hunter, Lawrence E. Kahn, Michael G. Computational Bioscience Program University of Colorado Anschutz Medical Campus AuroraCO80045 United States Department of Biomedical Informatics Columbia University Irving Medical Center New YorkNY10032 United States Department of Physical Medicine and Rehabilitation School of Medicine University of Colorado Anschutz Medical Campus AuroraCO80045 United States National Human Genome Research Institute National Institutes of Health BethesdaMD20892 United States Department of Computer Science Georgia State University AtlantaGA30303 United States Department of Biomedical Informatics University of Pittsburgh School of Medicine PittsburghPA15260 United States Computer Science Università degli Studi di Milano Milan20122 Italy Division of Environmental Genomics and Systems Biology Lawrence Berkeley National Laboratory BerkeleyCA94720 United States The Jackson Laboratory for Genomic Medicine FarmingtonCT06032 United States Department of Haematology University of Cambridge Cambridge United Kingdom Department of Research Informatics & Data Science Analytics Resource Center Children’s Hospital Colorado AuroraCO80045 United States University of Colorado Anschutz School of Medicine AuroraCO80045 United States Center for Health AI University of Colorado Anschutz Medical Campus AuroraCO80045 United States Departments of Biomedical Informatics and Pediatrics University of Colorado School of Medicine AuroraCO80045 United States Semanticly Athens Greece Yale School of Medicine New HavenCT06510 United States HealthLinc ValparaisoIN46383 United States Intelligent Systems Program University of Pittsburgh PittsburghPA15260 United States Department of Family Medicine University of Colorado Anschutz School of Medicine AuroraCO80045 United States Translational and Integrative Sciences Lab University of Colorado Anschutz Medical Campus AuroraCO80045 United States Tufts Institute for Clinical Research and Health Policy Studies Tufts University Bos

Background: Common data models solve many challenges of standardizing electronic health record (EHR) data, but are unable to semantically integrate all the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. Objective: We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Results: Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68-99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. Conclusions: By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping. © 2022, CC BY.

关键词： Ontology

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Biomedical discovery through the integrative biomedical knowledge hub (iBKH)

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iscience 2023年第4期26卷 106460页

作者： Su, Chang Hou, Yu Zhou, Manqi Rajendran, Suraj Maasch, Jacqueline R.M. A. Abedi, Zehra Zhang, Haotan Bai, Zilong Cuturrufo, Anthony Guo, Winston Chaudhry, Fayzan F. Ghahramani, Gregory Tang, Jian Cheng, Feixiong Li, Yue Zhang, Rui DeKosky, Steven T. Bian, Jiang Wang, Fei Department of Health Service Administration and Policy College of Public Health Temple University Philadelphia 19122 PA United States Department of Population Health Sciences Weill Cornell Medicine New York 10065 NY United States Department of Surgery University of Minnesota Minneapolis 55455 MN United States Department of Computational Biology Cornell University Ithaca 14850 NY United States Tri-Institutional Computational Biology & Medicine Program Cornell University New York 10065 NY United States Department of Computer Science Cornell Tech New York 10044 NY United States Department of Physiology and Biophysics Weill Cornell Medicine New York 10065 NY United States Computer Science Cornell University Ithaca 14850 NY United States Department of Medicine Weill Cornell Medicine New York 10021 NY United States Mila-Quebec AI Institute and HEC Montreal Montreal H2S 3H1 QC Canada Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Cleveland 44195 OH United States Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland 44195 OH United States Case Comprehensive Cancer Center Case Western Reserve University School of Medicine Cleveland 44106 OH United States School of Computer Science McGill University Montreal H3A 0C6 QC Canada Department of Neurology College of Medicine University of Florida Gainesville 32610 FL United States Department of Health Outcomes & Biomedical Informatics College of Medicine University of Florida Gainesville 32610 FL United States

The abundance of biomedical knowledge gained from biological experiments and clinical practices is an invaluable resource for biomedicine. The emerging biomedical knowledge graphs (BKGs) provide an efficient and effective way to manage the abundant knowledge in biomedical and life science. In this study, we created a comprehensive BKG called the integrative Biomedical Knowledge Hub (iBKH) by harmonizing and integrating information from diverse biomedical resources. To make iBKH easily accessible for biomedical research, we developed a web-based, user-friendly graphical portal that allows fast and interactive knowledge retrieval. Additionally, we also implemented an efficient and scalable graph learning pipeline for discovering novel biomedical knowledge in iBKH. As a proof of concept, we performed our iBKH-based method for computational in-silico drug repurposing for Alzheimer's disease. The iBKH is publicly available. © 2023 The Authors

关键词： Bioinformatics Drugs Systems biology

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Deciphering seasonal depression variations and interplays between weather changes, physical activity, and depression severity in real-world settings: Learnings from RADAR-MDD longitudinal mobile health study

arXiv

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arXiv 2024年

作者： Zhang, Yuezhou Folarin, Amos A. Ranjan, Yatharth Cummins, Nicholas Rashid, Zulqarnain Conde, Pauline Stewart, Callum Sun, Shaoxiong Vairavan, Srinivasan Matcham, Faith Oetzmann, Carolin Siddi, Sara Lamers, Femke Simblett, Sara Wykes, Til Mohr, David C. Haro, Josep Maria Penninx, Brenda W.J.H. Narayan, Vaibhav A. Hotopf, Matthew Dobson, Richard J.B. Pratap, Abhishek Department of Biostatistics & Health Informatics Institute of Psychiatry Psychology and Neuroscience King's College London London United Kingdom Institute of Health Informatics University College London London United Kingdom NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust London United Kingdom Health Data Research UK London University College London London United Kingdom NIHR Biomedical Research Centre University College London Hospitals NHS Foundation Trust London United Kingdom Department of Computer Science University of Sheffield Sheffield United Kingdom Janssen Research and Development LLC TitusvilleNJ United States Department of Psychological Medicine Institute of Psychiatry Psychology and Neuroscience King's College London London United Kingdom School of Psychology University of Sussex Falmer United Kingdom Teaching Research and Innovation Unit Parc Sanitari Sant Joan de Déu Fundació Sant Joan de Déu Barcelona Spain Centro de Investigación Biomédica en Red de Salud Mental Madrid Spain Department of Psychiatry Amsterdam UMC Vrije Universiteit Amsterdam Netherlands Mental Health Program Amsterdam Public Health Research Institute Amsterdam Netherlands Department of Psychology Institute of Psychiatry Psychology and Neuroscience King's College London London United Kingdom South London and Maudsley NHS Foundation Trust London United Kingdom Center for Behavioral Intervention Technologies Department of Preventive Medicine Northwestern University ChicagoIL United States Boehringer Ingelheim Pharmaceuticals Inc. RidgefieldCT United States University of Washington Seattle United States

Prior research has shown that changes in seasons and weather can have a significant impact on depression severity. However, findings are inconsistent across populations, and the interplay between weather, behavior, and depression has not been fully quantified. This study analyzed real-world data from 428 participants (a subset;68.7% of the cohort) in the RADAR-MDD longitudinal mobile health study to investigate seasonal variations in depression (measured through a remote validated assessment - PHQ-8) and examine the potential interplay between dynamic weather changes, physical activity (monitored via wearables), and depression severity. The clustering of PHQ-8 scores identified four distinct seasonal variations in depression severity: one stable trend and three varying patterns where depression peaks in different seasons. Among these patterns, participants within the stable trend had the oldest average age (p=0.002) and the lowest baseline PHQ-8 score (p=0.003). Mediation analysis assessing the indirect effect of weather on physical activity and depression showed significant differences among participants with different affective responses to weather. Specifically, the temperature and day length significantly influenced depression severity, which in turn impacted physical activity levels (p Copyright © 2024, The Authors. All rights reserved.

关键词： Radar measurement

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Training of Physical Neural Networks

arXiv

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arXiv 2024年

作者： Momeni, Ali Rahmani, Babak Scellier, Benjamin Wright, Logan G. McMahon, Peter L. Wanjura, Clara C. Li, Yuhang Skalli, Anas Berloff, Natalia G. Onodera, Tatsuhiro Oguz, Ilker Morichetti, Francesco del Hougne, Philipp Le Gallo, Manuel Sebastian, Abu Mirhoseini, Azalia Zhang, Cheng Marković, Danijela Brunner, Daniel Moser, Christophe Gigan, Sylvain Marquardt, Florian Ozcan, Aydogan Grollier, Julie Liu, Andrea J. Psaltis, Demetri Alù, Andrea Fleury, Romain Lausanne Switzerland Microsoft Research 198 Cambridge Science Park CambridgeCB4 0AB United Kingdom Rain AI San Francisco United States Department of Applied Physics Yale University CT United States School of Applied and Engineering Physics Cornell University IthacaNY14853 United States Max Planck Institute for the Science of Light Staudtstraße 2 Erlangen91058 Germany Department of Electrical and Computer Engineering University of California Los AngelesCA90095 United States FEMTO-ST Institute Optics Department CNRS University Bourgogne Franche-Comté Besançon25030 Cedex France Department of Applied Mathematics and Theoretical Physics University of Cambridge Cambridge United Kingdom NTT Physics and Informatics Laboratories NTT Research Inc. Sunnyvale United States Lausanne Switzerland Dipartimento di Elettronica Informazione e Bioingegneria Politecnico di Milano Milan Italy Univ Rennes CNRS IETR UMR 6164 RennesF-35000 France IBM Research Europe– Zurich Rüschlikon8803 Switzerland Department of Computer Science Stanford University United States Google DeepMind 1600 Amphitheatre Parkway Mountain ViewCA94043 United States Unité Mixte de Physique CNRS/Thales CNRS Thales Université Paris-Saclay Palaiseau France Laboratoire Kastler Brossel Sorbonne Université École Normale Supérieure Collège de France CNRS UMR 8552 Paris France Laboratoire Albert Fert CNRS Thales UniversitéParis-Saclay Palaiseau91767 France Department of Physics and Astronomy University of Pennsylvania PhiladelphiaPA19104 United States Lausanne Switzerland Photonics Initiative Advanced Science Research Center City University of New York New YorkNY10031 United States Physics Program Graduate Center City University of New York New YorkNY10016 United States

Physical neural networks (PNNs) are a class of neural-like networks that leverage the properties of physical systems to perform computation. While PNNs are so far a niche research area with small-scale laboratory demonstrations, they are arguably one of the most underappreciated important opportunities in modern artificial intelligence (AI). Could we train AI models 1000x larger than current ones? Could we do this and also have them perform inference locally and privately on edge devices, such as smartphones or sensors? Research over the past few years has shown that the answer to all these questions is likely "textityes, with enough research": PNNs could one day radically change what is possible and practical for AI systems. To do this will however require rethinking both how AI models work, and how they are trained – primarily by considering the problems through the constraints of the underlying hardware physics. To train PNNs at large scale, many methods including backpropagation-based and backpropagation-free approaches are now being explored. These methods have various trade-offs, and so far no method has been shown to scale to the same scale and performance as the backpropagation algorithm widely used in deep learning today. However, this is rapidly changing, and a diverse ecosystem of training techniques provides clues for how PNNs may one day be utilized to create both more efficient realizations of current-scale AI models, and to enable unprecedented-scale models. Copyright © 2024, The Authors. All rights reserved.

关键词： Deep learning

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Employing best input SVR robust lost function with nature-inspired metaheuristics in wind speed energy forecasting

IAENG International Journal of Computer Science

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IAENG International Journal of computer science 2020年第3期47卷 572-584页

作者： Caraka, Rezzy Eko Chen, Rung Ching Bakar, Sakhinah Abu Tahmid, Muhammad Toharudin, Toni Pardamean, Bens Huang, Su-Wen College of Informatics Chaoyang University of Technology Taichung City41349 Taiwan School of Mathematical Sciences The National University of Malaysia Bandar Baru Bangi Selangor43600 Malaysia Bioinformatics and Data Science Research Center Bina Nusantara University 11480 Indonesia Manado North Sulawesi91594 Indonesia Department of Statistics Padjadjaran University Jatinagor west java45363 Indonesia Bioinformatics and Data Science Research Center Bina Nusantara University and Computer Science Dept. BINUS Graduate Program-Master of Computer Science Program Bina Nusantara University Jakarta11480 Indonesia Taichung Veterans General Hospital Taiwan

Wind power has been experiencing a quick improvement. Without a doubt, wind is a variable asset that is hard to forecast. For instance, traditionally time series, extra holds are distributed to deal with this uncertainty. This paper presents a comparison of the performance of various Support Vector Regression (SVR) applied to short-term wind power forecasting. The analogy with BORUTA and multivariate adaptive regression splines (MARS) as judge best input and employ genetic algorithm and particle swarm optimization to find best parameter in Support Vector Regression with robust lost function. We measure the accuracy of this models by Symmetric means absolute percentage error (sMAPE) and we get the best model BORUTA-SVR-PSO with sMAPE 2.07155%. Moreover, we measure the energy conversion using Feedback Linearization Control (FLC). © International Association of Engineers.

关键词： Genetic algorithms

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Corrigendum to "Novel model of multiple sclerosis induced by EBV-like virus generate a unique B cell population" [Journal of Neuroimmunology volume 394 (2024) 578408]

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Journal of neuroimmunology 2025年 404卷 578625页

作者： J L Deffenbaugh K-J Jung S P Murphy Y Liu C N Rau C Petersen-Cherubini P L Collins D Chung A E Lovett-Racke Department of Microbial Infection & Immunity The Ohio State University Wexner Medical Center USA. Department of Computer Science and Engineering The Ohio State University USA. Department of Microbial Infection & Immunity The Ohio State University Wexner Medical Center USA Neuroscience Graduate Program The Ohio State University USA. Department of Biomedical Informatics The Ohio State University Wexner Medical Center USA Pelotonia Institute for Immuno-Oncology The Ohio State University Wexner Medical Center USA. Department of Neuroscience The Ohio State University Wexner Medical Center USA. Electronic address: amylovettracke@***.

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Feasibility study of Information Technology Investment (a case study of ODOO ERP: Project Management Module Implementation in Indonesia Based Company)

Feasibility study of Information Technology Investment (a ca...

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International Conference on ICT For Smart Society (ICISS)

作者： Fredy Jingga Raymond Kosala Suhono Harso Supangkat Benny Ranti Computer Science Department BINUS Graduate Program - Doctor of Computer Science Information Systems Department School of Information Systems Bina Nusantara University Jakarta Indonesia Computer Science Department BINUS Graduate Program - Doctor of Computer Science Bina Nusantara University Jakarta Indonesia School of Electrical Engineering and Informatics Bandung Institute of Technology Bandung Indonesia

IT Governance are one of the needs in managing Enterprise Level IT. This study shows part of the decision domain of IT Governance Help, which are IT Investment and Prioritization. The purpose of this study is to determine feasibility of implementation open source ERP system Odoo project management module that replaces current system based on operational, economic, and technical aspects. The method used are Fit / Gap Analysis and Cost Benefit model using economic impact worksheet. The analysis is done by comparing the requirement with features owned by current system and Odoo ERP system. This research resulted that Odoo ERP System is feasible in the 3 aspects, the operational feasibility Odoo reaching 72% Fit, the economic feasibility with ROI of 84%, and technical feasibility indicating the technical requirement can be fulfilled by leasing AWS server. The conclusion is the open source ERP system Odoo project management module is feasible to be applied in terms of 3 aspects that have been studied, those are operational, economic, and technical.

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On Performance Prediction of Big Data Transfer in High-performance Networks

On Performance Prediction of Big Data Transfer in High-perfo...

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IEEE International Conference on Communications (ICC)

作者： Wuji Liu Daqing Yun Chase Q. Wu Nageswara S.V. Rao Aiqin Hou Wei Shen Department of Computer Science New Jersey Institute of Technology Newark NJ USA Computer and Information Sciences Program Harrisburg University Harrisburg PA USA Computational Sciences and Engineering Division Oak Ridge National Laboratory Oak Ridge TN USA School of Information Science and Technology Northwest University Xi’an Shaanxi China School of Informatics Science and Technology Zhejiang Sci-Tech University Hangzhou Zhejiang China

ISBN: (数字)9781728150895

ISBN: (纸本)9781728150901

Big data generated by large-scale scientific and industrial applications need to be transferred between different geographical locations for remote storage, processing, and analysis. High-speed dedicated connections provisioned in High-performance Networks (HPNs) are increasingly utilized to carry out such big data transfer. HPN management highly relies on an important capability of performance (mainly throughput) prediction to reserve sufficient bandwidth and meanwhile avoid over-provisioning that may result in unnecessary resource waste. This capability is critical to improving the resource (mainly bandwidth) utilization of dedicated connections and meeting various user requests for data transfer. Conventional methods conduct performance prediction by fitting prior observed transfer history with predefined loss functions, without considering unobservable latent factors such as competing loads on end hosts. Such latent factors also have a significant impact on the application-level data transfer performance, which may result in an inaccurate prediction model. In this paper, we first investigate the impact of latent factors and propose a clustering-based method to eliminate their negative impact on performance prediction. We then develop a robust machine learning-based performance predictor by: i) incorporating the proposed latent factor elimination method into data preprocessing, and ii) adopting a customized domain guided loss function. Extensive experimental results show that our predictor achieves significantly higher prediction accuracy than several other state-of-the-art methods.

关键词： Data transfer Big Data Throughput Bandwidth Measurement Predictive models Protocols

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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries (vol 55, pg 89, 2023)

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NATURE GENETICS 2023年第3期55卷 519-520页

作者： Fernandez-Rozadilla, Ceres Timofeeva, Maria Chen, Zhishan Law, Philip Thomas, Minta Schmit, Stephanie Diez-Obrero, Virginia Hsu, Li Fernandez-Tajes, Juan Palles, Claire Sherwood, Kitty Briggs, Sarah Svinti, Victoria Donnelly, Kevin Farrington, Susan Blackmur, James Vaughan-Shaw, Peter Shu, Xiao-ou Long, Jirong Cai, Qiuyin Guo, Xingyi Lu, Yingchang Broderick, Peter Studd, James Huyghe, Jeroen Harrison, Tabitha Conti, David Dampier, Christopher Devall, Mathew Schumacher, Fredrick Melas, Marilena Rennert, Gad Obon-Santacana, Mireia Martin-Sanchez, Vicente Moratalla-Navarro, Ferran Oh, Jae Hwan Kim, Jeongseon Jee, Sun Ha Jung, Keum Ji Kweon, Sun-Seog Shin, Min-Ho Shin, Aesun Ahn, Yoon-Ok Kim, Dong-Hyun Oze, Isao Wen, Wanqing Matsuo, Keitaro Matsuda, Koichi Tanikawa, Chizu Ren, Zefang Gao, Yu-Tang Jia, Wei-Hua Hopper, John Jenkins, Mark Win, Aung Ko Pai, Rish Figueiredo, Jane Haile, Robert Gallinger, Steven Woods, Michael Newcomb, Polly Duggan, David Cheadle, Jeremy Kaplan, Richard Maughan, Timothy Kerr, Rachel Kerr, David Kirac, Iva Bohm, Jan Mecklin, Lukka-Pekka Jousilahti, Pekka Knekt, Paul Aaltonen, Lauri Rissanen, Harri Pukkala, Eero Eriksson, Johan Cajuso, Tatiana Hanninen, Ulrika Kondelin, Johanna Palin, Kimmo Tanskanen, Tomas Renkonen-Sinisalo, Laura Zanke, Brent Mannisto, Satu Albanes, Demetrius Weinstein, Stephanie Ruiz-Narvaez, Edward Palmer, Julie Buchanan, Daniel Platz, Elizabeth Visvanathan, Kala Ulrich, Cornelia Siegel, Erin Brezina, Stefanie Gsur, Andrea Campbell, Peter Chang-Claude, Jenny Hoffmeister, Michael Brenner, Hermann Slattery, Martha Potter, John Tsilidis, Konstantinos Schulze, Matthias Gunter, Marc Murphy, Neil Castells, Antoni Castellvi-Bel, Sergi Moreira, Leticia Arndt, Volker Shcherbina, Anna Stern, Mariana Pardamean, Bens Bishop, Timothy Giles, Graham Southey, Melissa Idos, Gregory McDonnell, Kevin Abu-Ful, Zomoroda Greenson, Joel Shulman, Katerina Lejbkowicz, Flavio Offit, Kenneth Su, Yu-Ru Steinfelder, Robert Keku, Temitope van Guelpen, Bethany Hudson, Thomas Hampel, Heather Pearlman, Edinburgh Cancer Research Centre Institute of Genomics and Cancer University of Edinburgh Edinburgh UK Genomic Medicine Group Instituto de Investigacion Sanitaria de Santiago Santiago de Compostela Spain Colon Cancer Genetics Group Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK Danish Institute for Advanced Study Department of Public Health University of Southern Denmark Odense Denmark Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University Medical Center Nashville TN USA Division of Genetics and Epidemiology Institute of Cancer Research London UK Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA Genomic Medicine Institute Cleveland Clinic Cleveland OH USA Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland OH USA Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute Barcelona Spain Oncology Data Analytics Program Catalan Institute of Oncology Barcelona Spain Consortium for Biomedical Research in Epidemiology and Public Health Madrid Madrid Spain Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain Department of Biostatistics School of Public Health University of Washington Seattle WA USA Institute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham UK Department of Public Health Richard Doll Building University of Oxford Oxford UK Department of Biomedical Informatics Vanderbilt University School of Medicine Nashville TN USA Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA Center for Public Health Genomics Department of Public Health Sciences University of Virginia Charlottesville VA USA Department of Populat

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

关键词： Colorectal cancer Epigenomics Genome-wide association studies Transcriptomics

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