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arXiv 2023年

作者： Barabási, Dániel L. Bianconi, Ginestra Bullmore, Ed Burgess, Mark Chung, SueYeon Eliassi-Rad, Tina George, Dileep Kovács, István A. Makse, Hernán Papadimitriou, Christos Nichols, Thomas E. Sporns, Olaf Stachenfeld, Kim Toroczkai, Zoltán Towlson, Emma K. Zador, Anthony M. Zeng, Hongkui Barabási, Albert-László Bernard, Amy Buzsáki, György Biophysics Program Harvard University CambridgeMA United States Department of Molecular and Cellular Biology Center for Brain Science Harvard University CambridgeMA United States School of Mathematical Sciences Queen Mary University of London LondonE1 4NS United Kingdom The Alan Turing Institute The British Library LondonNW1 2DB United Kingdom Department of Psychiatry Wolfson Brain Imaging Centre University of Cambridge Cambridge United Kingdom ChiTek-i AS Oslo Norway Center for Neural Science New York University New YorkNY United States Center for Computational Neuroscience Flatiron Institute Simons Foundation New YorkNY United States Network Science Institute Northeastern University BostonMA United States Khoury College of Computer Sciences Northeastern University BostonMA United States Santa Fe Institute Santa FeNM United States DeepMind United Kingdom Department of Physics and Astronomy Northwestern University 633 Clark Street EvanstonIL60208 United States Northwestern Institute on Complex Systems Chambers Hall Northwestern University 600 Foster St EvanstonIL60208 United States Levich Institute and Physics Department City College of New York New YorkNY10031 United States Columbia University New YorkNY10027 United States Big Data Institute Li Ka Shing Centre for Health Information and Discovery Nuffield Department of Population Health University of Oxford OxfordOX3 7LF United Kingdom Wellcome Centre for Integrative Neuroimaging FMRIB Nuffield Department of Clinical Neurosciences University of Oxford OxfordOX3 9DU United Kingdom Department of Psychological and Brain Sciences Indiana University BloomingtonIN47405 United States Department of Physics University of Notre Dame 225 Nieuwland Science Hall Notre DameIN46556 United States Department of Computer Science Department of Physics and Astronomy Hotchkiss Brain Institute Children’s Research Hospital University of Calgary CalgaryAB Canada Cold Spring Harbor Laboratory

The brain is a complex system comprising a myriad of interacting elements, posing significant challenges in understanding its structure, function, and dynamics. Network science has emerged as a powerful tool for studying such intricate systems, offering a framework for integrating multiscale data and complexity. Here, we discuss the application of network science in the study of the brain, addressing topics such as network models and metrics, the connectome, and the role of dynamics in neural networks. We explore the challenges and opportunities in integrating multiple data streams for understanding the neural transitions from development to healthy function to disease, and discuss the potential for collaboration between network science and neuroscience communities. We underscore the importance of fostering interdisciplinary opportunities through funding initiatives, workshops, and conferences, as well as supporting students and postdoctoral fellows with interests in both disciplines. By uniting the network science and neuroscience communities, we can develop novel network-based methods tailored to neural circuits, paving the way towards a deeper understanding of the brain and its functions. © 2023, CC BY-NC-SA.

关键词： Complex networks

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A method for comparing multiple imputation techniques: a case study on the U.S. National COVID Cohort Collaborative

arXiv

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arXiv 2022年

作者： Casiraghi, Elena Wong, Rachel Hall, Margaret Coleman, Ben Notaro, Marco Evans, Michael D. Tronieri, Jena S. Blau, Hannah Laraway, Bryan Callahan, Tiffany J. Chan, Lauren E. Bramante, Carolyn T. Buse, John B. Moffitt, Richard A. Stürmer, Til Johnson, Steven G. Shao, Yu Raymond Reese, Justin Robinson, Peter N. Paccanaro, Alberto Valentini, Giorgio Huling, Jared D. Wilkins, Kenneth J. Bennet, Tell Chute, Christopher DeWitt, Peter Gersing, Kenneth Girvin, Andrew Haendel, Melissa Harper, Jeremy Hajagos, Janos Hong, Stephanie Pfaff, Emily Reusch, Jane Antoniescu, Corneliu Robaski, Kimberly AnacletoLab Department of Computer Science "Giovanni degli Antoni" Università degli Studi di Milano Milan Italy CINI Infolife National Laboratory Roma Italy Department of Biomedical Informatics Stony Brook University Stony BrookNY United States The Jackson Laboratory for Genomic Medicine Farmington United States Institute for Systems Genomics University of Connecticut FarmingtonCT United States Biostatistical Design and Analysis Center Clinical and Translational Science Institute University of Minnesota MinneapolisMN United States Department of Psychiatry Perelman School of Medicine The University of Pennsylvania PhiladelphiaPA United States University of Colorado Anschutz Medical Campus AuroraCO United States College of Public Health and Human Sciences Oregon State University Corvallis United States Division of General Internal Medicine University of Minnesota MinneapolisMN United States NC Translational and Clinical Sciences Institute University of North Carolina at Chapel Hill Chapel HillNC United States Division of Endocrinology Department of Medicine University of North Carolina School of Medicine United States Department of Epidemiology Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel HillNC United States Institute for Health Informatics University of Minnesota MinneapolisMN United States 260 Longwood Ave Boston United States Department of Radiation Oncology UT Southwestern Medical Center Dallas United States Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory BerkeleyCA United States Fundação Getúlio Vargas Rio de Janeiro Brazil Department of Computer Science Royal Holloway University of London Egham United Kingdom Division of Biostatistics School of Public Health University of Minnesota MinneapolisMN United States Biostatistics Program Office of the Director National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of H

Healthcare datasets obtained from Electronic Health Records have proven to be extremely useful to assess associations between patients’ predictors and outcomes of interest. However, these datasets often suffer from missing values in a high proportion of cases and the simple removal of these cases may introduce severe bias. For these reasons, several multiple imputation algorithms have been proposed to attempt to recover the missing information. Each algorithm presents strengths and weaknesses, and there is currently no consensus on which multiple imputation algorithms works best in a given scenario. Furthermore, the selection of each algorithm parameters and data-related modelling choices are also both crucial and challenging. In this paper, we propose a novel framework to numerically evaluate strategies for handling missing data in the context of statistical analysis, with a particular focus on multiple imputation techniques. We demonstrate the feasibility of our approach on a large cohort of type-2 diabetes patients provided by the National COVID Cohort Collaborative (N3C) Enclave, where we explored the influence of various patient characteristics on outcomes related to COVID-19. Our analysis included classic multiple imputation techniques as well as simple complete-case Inverse Probability Weighted models. The experiments presented here show that our approach could effectively highlight the most valid and performant missing-data handling strategy for our case study. Moreover, our methodology allowed us to gain an understanding of the behavior of the different models and of how it changed as we modified their parameters. Our method is general and can be applied to different research fields and on datasets containing heterogeneous types. © 2022, CC BY-NC-ND.

关键词： Data handling

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Publisher Correction: The ENCODE Imputation Challenge: a critical assessment of methods for cross-cell type imputation of epigenomic profiles

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Genome biology 2025年第1期26卷 31页

作者： Jacob Matthew Schreiber Carles A Boix Jin Wook Lee Hongyang Li Yuanfang Guan Chun-Chieh Chang Jen-Chien Chang Alex Hawkins-Hooker Bernhard Schölkopf Gabriele Schweikert Mateo Rojas Carulla Arif Canakoglu Francesco Guzzo Luca Nanni Marco Masseroli Mark James Carman Pietro Pinoli Chenyang Hong Kevin Y Yip Jefrey P Spence Sanjit Singh Batra Yun S Song Shaun Mahony Zheng Zhang Wuwei Tan Yang Shen Yuanfei Sun Minyi Shi Jessika Adrian Richard S Sandstrom Nina P Farrell Jessica M Halow Kristen Lee Lixia Jiang Xinqiong Yang Charles B Epstein J Seth Strattan Bradley E Bernstein Michael P Snyder Manolis Kellis William S Noble Anshul Bharat Kundaje Department of Genetics Stanford University Stanford CA USA. jmschreiber91@***. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology Cambridge MA USA. Department of Genetics Stanford University Stanford CA USA. Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI USA. Department of Research and Development DeepSeq.AI San Francisco CA USA. RIKEN Center for Integrative Medical Sciences Yokohama Japan. Department of Empirical Inference Max Planck Institute for Intelligent Systems Stuttgart Germany. School of Life Sciences University of Dundee Dundee UK. Department of Electronics Information and Bioengineering Politecnico Di Milano Milan Italy. Department of Computational Biology University of Lausanne Lausanne Switzerland. Department of Computer Science and Engineering The Chinese University of Hong Kong Sha Tin Hong Kong. Sanford Burnham Prebys Medical Discovery Institute San Diego CA USA. Department of Electrical Engineering and Computer Sciences University of California Berkeley Berkeley CA USA. Department of Statistics University of California Berkeley Berkeley CA USA. Department of Biochemistry & Molecular Biology Center for Eukaryotic Gene Regulation Pennsylvania State University University Park PA USA. Department of Statistics Pennsylvania State University University Park PA USA. Department of Electrical and Computer Engineering Texas A&M University College Station TX USA. Altius Institute Seattle WA USA. Epigenomics Program The Broad Institute of MIT and Harvard Cambridge MA USA. Department of Genome Sciences University of Washington Seattle WA USA. Department of Computer Science Stanford University Stanford CA USA.

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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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Publisher Correction: Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors

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Nature genetics 2023年第1期55卷 166页

作者： Huipeng Li Elise T Courtois Debarka Sengupta Yuliana Tan Kok Hao Chen Jolene Jie Lin Goh Say Li Kong Clarinda Chua Lim Kiat Hon Wah Siew Tan Mark Wong Paul Jongjoon Choi Lawrence J K Wee Axel M Hillmer Iain Beehuat Tan Paul Robson Shyam Prabhakar Computational and Systems Biology Genome Institute of Singapore Singapore Singapore. Developmental Cellomics Laboratory Genome Institute of Singapore Singapore Singapore. Department of Computer Science and Engineering and Center for Computational Biology Indraprastha Institute of Information Technology Delhi India. Synthetic Biology Genome Institute of Singapore Singapore Singapore. Cancer Therapeutics and Stratified Oncology Genome Institute of Singapore Singapore Singapore. Department of Medical Oncology National Cancer Centre Singapore Singapore Singapore. Department of Pathology Singapore General Hospital Singapore Singapore. Department of Colorectal Surgery Singapore General Hospital Singapore Singapore. Data Analytics Department Institute for Infocomm Research Singapore Singapore. Cancer Therapeutics and Stratified Oncology Genome Institute of Singapore Singapore Singapore. iain.tan.b.h@singhealth.com.sg. Department of Medical Oncology National Cancer Centre Singapore Singapore Singapore. iain.tan.b.h@singhealth.com.sg. Program in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Singapore. iain.tan.b.h@singhealth.com.sg. Developmental Cellomics Laboratory Genome Institute of Singapore Singapore Singapore. paul.robson@***. The Jackson Laboratory for Genomic Medicine Farmington Connecticut USA. paul.robson@***. Department of Genetics and Genome Sciences Institute for Systems Genomics University of Connecticut Farmington Connecticut USA. paul.robson@***. Department of Biological Sciences National University of Singapore Singapore Singapore. paul.robson@***. Computational and Systems Biology Genome Institute of Singapore Singapore Singapore. prabhakars@gis.a-star.edu.sg.

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The application of an extracellular vesicle-based biosensor in early diagnosis and prediction of chemoresponsiveness in ovarian cancer

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Cancer Letters 2024年 581卷 216533-216533页

作者： Tsang, Benjamin K. Asare-Werehene, Meshach Hunter, Rob Gerber, Emma Reunov, Arkadiy Brine, Isaiah Chang, Chia-Yu Chang, Chia-Ching Shieh, Dar-Bin Burger, Dylan Anis, Hanan Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine Centre for Infection Immunity and Inflammation Interdisciplinary School of Health Sciences University of Ottawa Ottawa ON K1N 6N5 Canada Chronic Disease Program Ottawa Hospital Research Institute The Ottawa Hospital Ottawa ON K1Y 4E9 Canada Department of Biology St. Francis Xavier University 2320 Notre Dame Avenue Antigonish NS B2G 2W5 Canada School of Electrical Engineering and Computer Science Ottawa-Carleton Institute for Biomedical Engineering University of Ottawa Ottawa ON K1N 6N5 Canada Department of Biological Science and Department of Electrophysics Technology Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B) National Yang Ming Chiao Tung University Hsinchu 30068 Taiwan Institute of Basic Medical Science Institute of Oral Medicine and Department of Stomatology Advanced Optoelectronic Technology Center and Center for Micro/Nano Science and Technology National Cheng Kung University Hospital National Cheng Kung University Tainan 704 Taiwan Institute of Physics Academia Sinica Taipei 10529 Taiwan

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The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2

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四川生理科学杂志 2022年第7期44卷 1299-1299页

作者： Jonathan E Pekar Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA 92093 USA Department of Biomedical Informatics University of California San Diego La Jolla CA 92093 USA Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los Angeles CA 90095 USA Department of Immunology and Microbiology The Scripps Research Institute La Jolla CA 92037 USA Department of Computer Science and Engineering University of California San Diego La Jolla CA 92093 USA Department of Mathematics University of California San Diego La Jolla CA 92093 USA Department of Ecology and Evolutionary Biology University of Arizona Tucson AZ 85721 USA W. Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA New York City Public Health Laboratory New York City Department of Health and Mental Hygiene New York NY 11101 USA Department of Microbiology Institute for Viral Diseases Biosafety Center College of Medicine Korea University Seoul South Korea BK21 Graduate Program Department of Biomedical Sciences Korea University College of Medicine Seoul 02841 Republic of Korea National Public Health Laboratory National Centre for Infectious Diseases Singapore Malaysia Genome and Vaccine Institute Jalan Bangi 43000 Kajang Selangor Malaysia Department of Medicine University of California San Diego La Jolla CA 92093 USA Department of Microbiology and Immunology School of Medicine Tulane University New Orleans LA 70112 USA Zalgen Labs Frederick MD 21703 USA Global Virus Network (GVN) Baltimore MD 21201 USA Sydney Institute for Infectious Diseases School of Life and Environmental Sciences and School of Medical Sciences The University of Sydney Sydney NSW 2006 Australia Institute of Evolutionary Biology University of Edinburgh King’s Buildings Edinburgh EH9 3FL UK Department of Biomathematics David Geffen School of Medicine Un

Understanding the circumstances that lead to pandemics is important for their prevention. Here, we analyze the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic. We show that SARS-CoV-2 genomic diversity before February 2020 likely comprised only two distinct viral lineages, denoted A and B. Phylodynamic rooting methods, coupled with epidemic simulations, reveal that these lineages were the result of at least two separate cross-species transmission events into humans. The first zoonotic transmission likely involved lineage B viruses around 18 November 2019 (23 October-8 December), while the separate introduction of lineage A likely occurred within weeks of this event.

关键词： epidemiology likely acute

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AIRR community curation and standardised representation for immunoglobulin and T cell receptor germline sets

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Immunoinformatics (Amsterdam, Netherlands) 2023年 10卷 100025页

作者： William D Lees Scott Christley Ayelet Peres Justin T Kos Brian Corrie Duncan Ralph Felix Breden Lindsay G Cowell Gur Yaari Martin Corcoran Gunilla B Karlsson Hedestam Mats Ohlin Andrew M Collins Corey T Watson Christian E Busse Institute of Structural and Molecular Biology Birkbeck College London England. Human-Centered Computing and Information Science Institute for Systems and Computer Engineering Technology and Science Porto Portugal. Peter O'Donnell Jr. School of Public Health UT Southwestern Medical Center Dallas TX USA. Bioengineering Program Faculty of Engineering Bar-Ilan University Ramat Gan Israel. Department of Biochemistry and Molecular Genetics School of Medicine University of Louisville KY USA. Department of Biological Sciences Simon Fraser University Burnaby BC Canada. Fred Hutchinson Cancer Research Center Seattle WA USA. Peter O'Donnell Jr. School of Public Health Department of Immunology School of Biomedical Sciences UT Southwestern Medical Center Dallas TX USA. Department of Microbiology Tumor and Cell Biology Karolinska Institutet Stockholm Swede. Department of Immunotechnology and SciLifeLab Lund University Lund Sweden. School of Biotechnology and Biomolecular Sciences University of New South Wales Sydney NSW Australia. Division of B Cell Immunology German Cancer Research Center Heidelberg Germany.

Analysis of an individual's immunoglobulin or T cell receptor gene repertoire can provide important insights into immune function. High-quality analysis of adaptive immune receptor repertoire sequencing data depends upon accurate and relatively complete germline sets, but current sets are known to be incomplete. Established processes for the review and systematic naming of receptor germline genes and alleles require specific evidence and data types, but the discovery landscape is rapidly changing. To exploit the potential of emerging data, and to provide the field with improved state-of-the-art germline sets, an intermediate approach is needed that will allow the rapid publication of consolidated sets derived from these emerging sources. These sets must use a consistent naming scheme and allow refinement and consolidation into genes as new information emerges. Name changes should be minimised, but, where changes occur, the naming history of a sequence must be traceable. Here we outline the current issues and opportunities for the curation of germline IG/TR genes and present a forward-looking data model for building out more robust germline sets that can dovetail with current established processes. We describe interoperability standards for germline sets, and an approach to transparency based on principles of findability, accessibility, interoperability, and reusability.

关键词： AIRR-seq Immune receptor Immune receptor germline Immune receptor repertoire Rep-seq

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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Considering discrepancy when calibrating a mechanistic electrophysiology model

arXiv

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arXiv 2020年

作者： Lei, Chon Lok Ghosh, Sanmitra Whittaker, Dominic G. Aboelkassem, Yasser Beattie, Kylie A. Cantwell, Chris D. Delhaas, Tammo Houston, Charles Novaes, Gustavo Montes Panfilov, Alexander V. Pathmanathan, Pras Riabiz, Marina Weber dos Santos, Rodrigo Worden, Keith Mirams, Gary R. Wilkinson, Richard D. Computational Biology & Health Informatics Dept. of Computer Science University of Oxford United Kingdom MRC Biostatistics Unit University of Cambridge United Kingdom Centre for Mathematical Medicine & Biology School of Mathematical Sciences University of Nottingham United Kingdom Department of Bioengineering University of California San Diego United States Systems Modeling and Translational Biology GlaxoSmithKline R&D Stevenage United Kingdom ElectroCardioMaths Programme Centre for Cardiac Engineering Imperial College London United Kingdom CARIM School for Cardiovascular Diseases Maastricht University Netherlands Graduate Program in Computational Modeling Universidade Federal de Juiz de Fora Brazil Department of Physics and Astronomy Ghent University Belgium Laboratory of Computational Biology and Medicine Ural Federal University Ekaterinburg Russia U.S. Food and Drug Administration Center for Devices and Radiological Health Office of Science and Engineering Laboratories United States Department of Biomedical Engineering King’s College London Alan Turing Institute United Kingdom Dynamics Research Group Department of Mechanical Engineering University of Sheffield United Kingdom School of Mathematics and Statistics University of Sheffield United Kingdom

Uncertainty quantification (UQ) is a vital step in using mathematical models and simulations to take decisions. The field of cardiac simulation has begun to explore and adopt UQ methods to characterise uncertainty in model inputs and how that propagates through to outputs or predictions. In this perspective piece we draw attention to an important and under-addressed source of uncertainty in our predictions — that of uncertainty in the model structure or the equations themselves. The difference between imperfect models and reality is termed model discrepancy, and we are often uncertain as to the size and consequences of this discrepancy. Here we provide two examples of the consequences of discrepancy when calibrating models at the ion channel and action potential scales. Furthermore, we attempt to account for this discrepancy when calibrating and validating an ion channel model using different methods, based on modelling the discrepancy using Gaussian processes (GPs) and autoregressive-moving-average (ARMA) models, then highlight the advantages and shortcomings of each approach. Finally, suggestions and lines of enquiry for future work are provided. Copyright © 2020, The Authors. All rights reserved.

关键词： Uncertainty analysis

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