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Transcript expression-aware annotation improves rare variant interpretation (vol 581, pg 452, 2020)

NATURE 2021年第7846期590卷 E54-E54页

作者： Cummings, Beryl B. Karczewski, Konrad J. Kosmicki, Jack A. Seaby, Eleanor G. Watts, Nicholas A. Singer-Berk, Moriel Mudge, Jonathan M. Karjalainen, Juha Satterstrom, F. Kyle O'Donnell-Luria, Anne H. Poterba, Timothy Seed, Cotton Solomonson, Matthew Alfoldi, Jessica Daly, Mark J. MacArthur, Daniel G. Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Analytical and Translational Genetics Unit Massachusetts General Hospital Boston MA USA Program in Biological and Biomedical Sciences Harvard Medical School Boston MA USA Program in Bioinformatics and Integrative Genomics Harvard Medical School Boston MA USA Genomic Informatics Group University Hospital Southampton Southampton UK Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA USA Division of Genetics and Genomics Boston Children’s Hospital Boston MA USA Department of Pediatrics Harvard Medical School Boston MA USA European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge UK Center for Genomic Medicine Massachusetts General Hospital Boston MA USA Broad Genomics Broad Institute of MIT and Harvard Cambridge MA USA National Heart & Lung Institute and MRC London Institute of Medical Sciences Imperial College London London UK Cardiovascular Research Centre Royal Brompton & Harefield Hospitals NHS Trust London UK Cardiac Arrhythmia Service and Cardiovascular Research Center Massachusetts General Hospital Boston MA USA Estonian Genome Center Institute of Genomics University of Tartu Tartu Estonia Department of Medicine Harvard Medical School Boston MA USA Cardiac Arrhythmia Service Massachusetts General Hospital Boston MA USA Division of General Internal Medicine Massachusetts General Hospital Boston MA USA Institute for Molecular Medicine FIMM University of Helsinki Helsinki Finland Department of Public Health Faculty of Medicine University of Helsinki Helsinki Finland Department of Genetics Harvard Medical School Boston MA USA Data Sciences Platform Broad Institute of MIT and Harvard Cambridge MA USA Genomics Platform Broad Institute of MIT and Harvard Cambridge MA USA Wellcome Sanger Institute Hinxton Cambridgeshire UK Unidad de Investigaci

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Evolution Arrests Invasions of Cooperative Populations

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Physical Review Letters 2015年第20期115卷 208104-208104页

作者： Kirill S. Korolev Department of Physics and Graduate Program in Bioinformatics Boston University Boston Massachusetts 02215 USA

Population expansions trigger many biomedical and ecological transitions, from tumor growth to invasions of non-native species. Although population spreading often selects for more invasive phenotypes, we show that this outcome is far from inevitable. In cooperative populations, mutations reducing dispersal have a competitive advantage. Such mutations then steadily accumulate at the expansion front, bringing invasion to a halt. Our findings are a rare example of evolution driving the population into an unfavorable state, and they could lead to new strategies to combat unwelcome invaders.

关键词： Evolutionary dynamics Mutation

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Public Good Diffusion Limits Microbial Mutualism

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Physical Review Letters 2015年第16期114卷 168102-168102页

作者： Rajita Menon Kirill S. Korolev Department of Physics and Graduate Program in Bioinformatics Boston University Boston Massachusetts 02215 USA

Standard game theory cannot describe microbial interactions mediated by diffusible molecules. Nevertheless, we show that one can still model microbial dynamics using game theory with parameters renormalized by diffusion. Contrary to expectations, greater sharing of metabolites reduces the strength of cooperation and leads to species extinction via a nonequilibrium phase transition. We report analytic results for the critical diffusivity and the length scale of species intermixing. Species producing slower public good is favored by selection when fitness saturates with nutrient concentration.

关键词： GAME theory MICROBIAL diversity METABOLITES DIFFUSION -- Measurement MUTUALISM

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Systems biology applications to study mechanisms of human immunodeficiency virus latency and reactivation

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World Journal of Clinical Infectious Diseases 2016年第2期6卷 6-21页

作者： Cory H White Bastiaan Moesker Angela Ciuffi Nadejda Beliakova-Bethell Graduate Program in Bioinformatics and Systems Biology University of California San Diego San Diego VA Medical Center and Veterans Medical Research Foundation Clinical and Experimental Sciences Faculty of Medicine University of Southampton Institute of Microbiology University Hospital of Lausanne (CHUV) and University of Lausanne Department of Medicine Univer-sity of California San Diego

Eradication of human immunodeficiency virus(HIV) in infected individuals is currently not possible because of the presence of the persistent cellular reservoir of latent infection. The identification of HIV latency biomarkers and a better understanding of the molecular mechanisms contributing to regulation of HIV expression might provide essential tools to eliminate these latently infected cells. This review aims at summarizing gene expression profiling and systems biology applications to studies of HIV latency and eradication. Studies comparing gene expression in latently infected and uninfected cells identify candidate latency biomarkers and novel mechanisms of latency control. Studies that profiled gene expression changes induced by existing latency reversing agents(LRAs) highlight uniting themes driving HIV reactivation and novel mechanisms that contribute to regulation of HIV expression by different LRAs. Among the reviewed gene expression studies, the common approaches included identification of differentially expressed genes and gene functional category assessment. Integration of transcriptomic data with other biological data types is presently scarce, and the field would benefit from increased adoption of these methods in future studies. In addition, designing prospective studies that use the same methods of data acquisition and statistical analyses will facilitate a more reliableidentification of latency biomarkers using different model systems and the comparison of the effects of different LRAs on host factors with a role in HIV reactivation. The results from such studies would have the potential to significantly impact the process by which candidate drugs are selected and combined for future evaluations and advancement to clinical trials.

关键词： Gene expression Microarrays RNA-Seq Systems biology Human immunodeficiency virus Viral latency Disease eradication Biomarkers Molecular mechanisms Latency reversing agents

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Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

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Science (New York, N.Y.) 2025年第6734期387卷 eadp4753页

作者： Liu, Hongbo Abedini, Amin Ha, Eunji Ma, Ziyuan Sheng, Xin Dumoulin, Bernhard Qiu, Chengxiang Aranyi, Tamas Li, Shen Dittrich, Nicole Chen, Hua-Chang Tao, Ran Tarng, Der-Cherng Hsieh, Feng-Jen Chen, Shih-Ann Yang, Shun-Fa Lee, Mei-Yueh Kwok, Pui-Yan Wu, Jer-Yuarn Chen, Chien-Hsiun Khan, Atlas Limdi, Nita A. Wei, Wei-Qi Walunas, Theresa L. Karlson, Elizabeth W. Kenny, Eimear E. Luo, Yuan Kottyan, Leah Connolly, John J. Jarvik, Gail P. Weng, Chunhua Shang, Ning Cole, Joanne B. Mercader, Josep M. Mandla, Ravi Majarian, Timothy D. Florez, Jose C. Haas, Mary E. Lotta, Luca A. Drivas, Theodore G. Vy, Ha My T Nadkarni, Girish N. Wiley, Laura K. Wilson, Melissa P. Gignoux, Christopher R. Rasheed, Humaira Thomas, Laurent F. Åsvold, Bjørn Olav Brumpton, Ben M. Hallan, Stein I. Hveem, Kristian Zheng, Jie Hellwege, Jacklyn N. Zawistowski, Matthew Zöllner, Sebastian Franceschini, Nora Hu, Hailong Zhou, Jianfu Kiryluk, Krzysztof Ritchie, Marylyn D. Palmer, Matthew Edwards, Todd L. Voight, Benjamin F. Hung, Adriana M. Susztak, Katalin Department of Medicine Renal Electrolyte and Hypertension Division University of Pennsylvania Philadelphia PA United States Institute of Diabetes Obesity and Metabolism University of Pennsylvania Philadelphia PA United States Department of Genetics University of Pennsylvania Philadelphia PA United States Penn-CHOP Kidney Innovation Center University of Pennsylvania Philadelphia PA United States Liangzhu Laboratory Zhejiang University 1369 West Wenyi Road Hangzhou Zhejiang China Department of Nephrology Children' Hospital Zhejiang University School of Medicine National Clinical Research Center for Child Health Hangzhou Zhejiang China Institute of Molecular Life Sciences HUN-REN Research Center for Natural Sciences Budapest Hungary Department of Molecular Biology Semmelweis University Budapest Hungary Department of Medicine Federal University of São Paulo São Paulo Brazil Department of Biostatistics Vanderbilt University Medical Center Nashville TN United States Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville TN United States Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Division of Nephrology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Institute of Biomedical Sciences Academia Sinica ROC Taipei Taiwan Cardiovascular Center Taichung Veterans General Hospital Taichung Taiwan ROC National Chung Hsing University Taichung Taiwan ROC Heart Rhythm Center Division of Cardiology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Department of Internal Medicine College of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan ROC Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan ROC Division of Endocrinology and Metabolism Department of Internal Medicine Kaohsiung Medical Universit

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the "Kidney Disease Genetic Scorecard" for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.

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Rejection of aliases for a direct sampling mixer with complex poles

IEEJ Transactions on Electronics, Information and Systems

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IEEJ Transactions on Electronics, Information and Systems 2016年第1期136卷 60-67页

作者： Imai, Hiroyuki Wada, Kazuyuki Electrical Engineering Program Graduate School of Science and Technology Meiji University 1-1-1 Higashi-Mita Tama-ku Kawasaki214-8571 Japan Department of Electronics and Bioinformatics School of Science and Technology Meiji University 1-1-1 Higashi-Mita Tama-ku Kawasaki214-8571 Japan

This paper proposes the design scheme of direct sampling mixer (DSM) by which unallowable amplitude characteristics due to aliases spreading over relatively broad band is suppressed. It is pointed out that the periodic frequency characteristic of a stage processing decimated signal causes decrease of attenuation in the stopband of the DSM, and an IIR section with a low decimation rate is employed as the first stage. A DSM the amplitude characteristic of which falls into the spectrum mask for IEEE 802.11 is designed as an example. Simulation results show that the designed DSM satisfies specification widely in not only the passband but also the stopband. It is confirmed that gradual decimation approach or use of a non-decimated section for the first stage is effective. © 2016 The Institute of Electrical Engineers of Japan.

关键词： Bandpass filters

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Implementing globally unique identifier architecture in date collection for a health management study in taiwan aboriginal tribe 1

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9th FTRA International Conference on Future Information Technology, FutureTech 2014

作者： Hung, Jui-Fu Rau, Hsiao-Hsien Hsu, Chien-Yeh Chen, Shih-Chang Tsai, Duu-Jian Fann, Yang Park, Joshua Eng, Joshua Graduate Institute of Biomedical Informatics Taipei Medical University Taipei Taiwan Graduate Institute of Patent National Taiwan University of Science and Technology Taipei Taiwan Intramural IT and Bioinformatics Program NINDS NIH HHS Bethesda United States

ISBN: (数字)9789401795586

ISBN: (纸本)9789401795579

In present, more and more attention has been put on the effort of protection of personal data and also new encryption technologies are derived. In this article, we introduce a personal information protection technology, global unique identifier (GUID), which is developed by National Institutes of Health U.S. and used for personal health information protection. The GUID is an identifier that allows researchers to associate and share data specific to a study participant without using or exposing personally identifiable information (PII). The GUID is made up of random alphanumeric characters and is not directly generated from PII/Protected Health Information (PHI). It has been approved by the NIH/USA office General Counsel for secure sharing of anonymized database. In our study, we used GUID as key identifier for health data collection from aboriginal tribe in a health promotion project. © Springer Science+Business Media Dordrecht 2015.

关键词： Cryptography

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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

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Translational psychiatry 2024年第1期14卷 109页

作者： Anna H Ou Sara B Rosenthal Mazda Adli Kazufumi Akiyama Nirmala Akula Martin Alda Azmeraw T Amare Raffaella Ardau Bárbara Arias Jean-Michel Aubry Lena Backlund Michael Bauer Bernhard T Baune Frank Bellivier Antonio Benabarre Susanne Bengesser Abesh Kumar Bhattacharjee Joanna M Biernacka Pablo Cervantes Guo-Bo Chen Hsi-Chung Chen Caterina Chillotti Sven Cichon Scott R Clark Francesc Colom David A Cousins Cristiana Cruceanu Piotr M Czerski Clarissa R Dantas Alexandre Dayer Maria Del Zompo Franziska Degenhardt J Raymond DePaulo Bruno Étain Peter Falkai Frederike Tabea Fellendorf Ewa Ferensztajn-Rochowiak Andreas J Forstner Louise Frisén Mark A Frye Janice M Fullerton Sébastien Gard Julie S Garnham Fernando S Goes Maria Grigoroiu-Serbanescu Paul Grof Oliver Gruber Ryota Hashimoto Joanna Hauser Urs Heilbronner Stefan Herms Per Hoffmann Andrea Hofmann Liping Hou Stephane Jamain Esther Jiménez Jean-Pierre Kahn Layla Kassem Tadafumi Kato Sarah Kittel-Schneider Barbara König Po-Hsiu Kuo Ichiro Kusumi Nina Lackner Gonzalo Laje Mikael Landén Catharina Lavebratt Marion Leboyer Susan G Leckband Carlos A López Jaramillo Glenda MacQueen Mario Maj Mirko Manchia Cynthia Marie-Claire Lina Martinsson Manuel Mattheisen Michael J McCarthy Susan L McElroy Francis J McMahon Philip B Mitchell Marina Mitjans Francis M Mondimore Palmiero Monteleone Caroline M Nievergelt Markus M Nöthen Tomas Novák Urban Ösby Norio Ozaki Sergi Papiol Roy H Perlis Claudia Pisanu James B Potash Andrea Pfennig Daniela Reich-Erkelenz Andreas Reif Eva Z Reininghaus Marcella Rietschel Guy A Rouleau Janusz K Rybakowski Martin Schalling Peter R Schofield K Oliver Schubert Thomas G Schulze Barbara W Schweizer Florian Seemüller Giovanni Severino Tatyana Shekhtman Paul D Shilling Kazutaka Shimoda Christian Simhandl Claire M Slaney Alessio Squassina Thomas Stamm Pavla Stopkova Sarah K Tighe Alfonso Tortorella Gustavo Turecki Eduard Vieta Julia Volkert Stephanie Witt Naomi R Wray Adam Wright L Trevor Young Peter P Zandi John R Kelsoe Department of Psychiatry University of California San Diego La Jolla CA USA. Center for Computational Biology and Bioinformatics Department of Medicine University of California San Diego La Jolla CA USA. Department of Psychiatry and Psychotherapy Charité- Universitätsmedizin Berlin Campus Charité Mitte Berlin Germany. Fliedner Klinik Berlin Center for Psychiatry Psychotherapy and Psychosomatic Medicine Berlin Germany. Department of Biological Psychiatry and Neuroscience Dokkyo Medical University School of Medicine Mibu Japan. Intramural Research Program National Institute of Mental Health National Institutes of Health US Department of Health & Human Services Bethesda MD USA. Department of Psychiatry Dalhousie University Halifax NS Canada. National Institute of Mental Health Klecany Czech Republic. Discipline of Psychiatry University of Adelaide Adelaide SA Australia. Unit of Clinical Pharmacology Hospital University Agency of Cagliari Cagliari Italy. Department of Evolutive Biology Ecology and Environmental Sciences Facultat de Biologia and Institut de Biomedicina (IBUB) Universitat de Barcelona Barcelona Spain. CIBER de Salud Mental ISCIII Madrid Barcelona Catalonia Spain. Department of Mental Health and Psychiatry Mood Disorders Unit-Geneva University Hospitals Geneva Switzerland. Department of Molecular Medicine and Surgery Karolinska Institutet and Center for Molecular Medicine Karolinska University Hospital Stockholm Sweden. Department of Psychiatry and Psychotherapy University Hospital Carl Gustav Carus Medical Faculty Technische Universität Dresden Dresden Germany. Department of Psychiatry University of Münster Münster Germany. INSERM UMR-S 1144-Université Paris Cité Département de Psychiatrie et de Médecine Addictologique AP-HP Groupe Hospitalier Lariboisière-F Widal Paris France. Bipolar and Depressive Disorders Unit Institute of Neuroscience Hospital Clinic University of Barcelona IDIBAPS CIBERSAM ISCIII Barcelona Catalonia Spa

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

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Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan

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European journal of medical research 2024年第1期29卷 286页

作者： Wen-Chien Cheng Chia-Ling Chang Chau-Chyun Sheu Ping-Huai Wang Meng-Heng Hsieh Ming-Tsung Chen Wei-Fan Ou Yu-Feng Wei Tsung-Ming Yang Chou-Chin Lan Cheng-Yi Wang Chih-Bin Lin Ming-Shian Lin Yao-Tung Wang Ching-Hsiung Lin Shih-Feng Liu Meng-Hsuan Cheng Yen-Fu Chen Chung-Kan Peng Ming-Cheng Chan Ching-Yi Chen Lun-Yu Jao Ya-Hui Wang Chi-Jui Chen Shih-Pin Chen Yi-Hsuan Tsai Shih-Lung Cheng Horng-Chyuan Lin Jung-Yien Chien Hao-Chien Wang Wu-Huei Hsu Division of Pulmonary and Critical Care Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan. wcchengdr@***. Critical Medical Center China Medical University Hospital Taichung Taiwan. wcchengdr@***. School of Medicine College of Medicine China Medical University Taichung Taiwan. wcchengdr@***. Department of Internal Medicine National Taiwan University Hospital Hsin-Chu Branch Hsin-Chu Taiwan. Graduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei Taiwan. Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Taiwan. Department of Internal Medicine School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan. Division of Thoracic Medicine Far Eastern Memorial Hospital Taipei Taiwan. Department of Thoracic Medicine Chang Gung Memorial Hospital at Linkou Taoyuan Taiwan. College of Medicine Chang Gung University Taoyuan Taiwan. Division of Pulmonary and Critical Care Medicine Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei Taiwan. Division of Chest Medicine Department of Internal Medicine Taichung Veterans General Hospital Taichung Taiwan. Department of Internal Medicine E-Da Cancer Hospital I-Shou University Kaohsiung Taiwan. School of Medicine for International Students College of Medicine I-Shou University Kaohsiung Taiwan. Division of Pulmonary and Critical Care Medicine Chiayi Chang Gung Memorial Hospital Chiayi Taiwan. Division of Pulmonary Medicine Department of Internal Medicine Taipei Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation New Taipei City Taiwan Republic of China. Department of Internal Medicine Cardinal Tien Hospital and School of Medicine College of Medicine Fu Jen Catholic University New Taipei City Taiwan. Division of Pulmonary Medicine Department of Internal Medicine Hualien Tzu Chi Hospital Buddhi

BACKGROUND:Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS:This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS:Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION:Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

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A structural variation reference for medical and population genetics (vol 581, pg 444, 2020)

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NATURE 2021年第7846期590卷 E55-E55页

作者： Collins, Ryan L. Brand, Harrison Karczewski, Konrad J. Zhao, Xuefang Alfoldi, Jessica Francioli, Laurent C. Khera, Amit V. Lowther, Chelsea Gauthier, Laura D. Wang, Harold Watts, Nicholas A. Solomonson, Matthew O'Donnell-Luria, Anne Baumann, Alexander Munshi, Ruchi Walker, Mark Whelan, Christopher W. Huang, Yongqing Brookings, Ted Sharpe, Ted Stone, Matthew R. Valkanas, Elise Fu, Jack Tiao, Grace Laricchia, Kristen M. Ruano-Rubio, Valentin Stevens, Christine Gupta, Namrata Cusick, Caroline Margolin, Lauren Taylor, Kent D. Lin, Henry J. Rich, Stephen S. Post, Wendy S. Chen, Yii-Der Ida Rotter, Jerome I. Nusbaum, Chad Philippakis, Anthony Lander, Eric Gabriel, Stacey Neale, Benjamin M. Kathiresan, Sekar Daly, Mark J. Banks, Eric MacArthur, Daniel G. Talkowski, Michael E. Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USA Center for Genomic Medicine Massachusetts General Hospital Boston MA USA Division of Medical Sciences Harvard Medical School Boston MA USA Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston MA USA Analytical and Translational Genetics Unit Massachusetts General Hospital Boston MA USA Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA Department of Medicine Harvard Medical School Boston MA USA Data Science Platform Broad Institute of MIT and Harvard Cambridge MA USA Broad Genomics Broad Institute of MIT and Harvard Cambridge MA USA European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge UK Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA USA Division of Genetics and Genomics Boston Children’s Hospital Boston MA USA Department of Pediatrics Harvard Medical School Boston MA USA National Heart & Lung Institute and MRC London Institute of Medical Sciences Imperial College London London UK Cardiovascular Research Centre Royal Brompton & Harefield Hospitals NHS Trust London UK Cardiac Arrhythmia Service Cardiovascular Research Center Massachusetts General Hospital Boston MA USA Estonian Genome Center Institute of Genomics University of Tartu Tartu Estonia Diabetes Unit Massachusetts General Hospital Boston MA USA Program in Metabolism Broad Institute of MIT and Harvard Cambridge MA USA Division of Cardiology Massachusetts General Hospital Boston MA USA Cardiovascular Disease Initiative Broad Institute of MIT and Harvard Cambridge MA USA Division of General Internal Medicine Massachusetts General Hospital Boston MA USA Institute for Molecular Medicine Finland (FIMM) HiLIFE University of Helsinki Helsinki Finland Department of Public Health Faculty of Medicine University

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