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Precision probiotics supplement strategy in aging population based on gut microbiome composition

Briefings in bioinformatics 2024年第4期25卷 bbae351页

作者： Yi-Fang Chuang Kang-Chen Fan Yin-Yuan Su Ming-Fong Wu Yen-Ling Chiu Yi-Chien Liu Chen-Ching Lin School of Medicine National Yang Ming Chiao Tung University No. 155 Sec. 2 Linong St. Beitou Dist. Taipei City 112304 Taiwan. Institute of Public Health National Yang Ming Chiao Tung University No. 155 Sec. 2 Linong St. Beitou Dist. Taipei City 112304 Taiwan. Department of Psychiatry Far Eastern Memorial Hospital No. 21 Sec. 2 Nanya S. Rd. Banqiao Dist. New Taipei City 220216 Taiwan. Institute of Biomedical Informatics National Yang Ming Chiao Tung University No. 155 Sec. 2 Linong St. Beitou Dist. Taipei City 112304 Taiwan. Department of Medical Research Far Eastern Memorial Hospital No. 21 Sec. 2 Nanya S. Rd. Banqiao Dist. New Taipei City 220216 Taiwan. Graduate Program in Biomedical Informatics and Graduate Institute of Medicine Yuan Ze University No. 135 Yuandong Rd. Zhongli Dist. Taoyuan City 320315 Taiwan. Graduate Institute of Clinical Medicine National Taiwan University No. 1 Sec. 4 Roosevelt Rd. Taipei City 106319 Taiwan. Department of Neurology Cardinal Tien Hospital No. 362 Zhongzheng Rd. Xindian Dist. New Taipei City 231009 Taiwan.

With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.

关键词： consensus clustering gut microbiome metagenomics non-negative matrix factorization older adults precision probiotics

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Proceedings of the 16th Annual UT-KBRIN Bioinformatics Summit 2016: bioinformatics

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BMC Bioinformatics 2017年第9期18卷 1-9页

作者： Eric C. Rouchka Juw Won Park Julia H. Chariker David A. Tieri Shreedharkumar Rajurkar Vikas Singh Nishchal K. Verma Yan Cui Mark Farman Bradford Condon Jolanta Jaromczyk Neil Moore Jerzy Jaromczyk Daniel Harris Patrick Calie Eun Kyong Shin Robert L. Davis Arash Shaban-Nejad Joshua M. Mitchell Hunter N. B. Moseley Robert M. Flight Qing Jun Wang Richard M. Higashi Teresa W-M Fan Andrew N. Lane Liangqun Lu Bernie J Daigle Jr. Xi Chen Andrey Smelter Jerzy W. Jaromczyk Bailey K. Phan Nathaniel J. Serpico Ethan G. Toney Li Chen Caroline E. Melton Jennifer R. Mandel Bernie J. Daigle Jr. Hao Chen Kazi I. Zaman Ramin Homayouni Patrick J. Trainor Andrew P. DeFilippis Samantha M. Carlisle Shesh N. Rai Department of Computer Engineering and Computer Science University of Louisville Duthie Center for Engineering Louisville KY 40292 USA Kentucky Biomedical Research Infrastructure (KBRIN) Bioinformatics Core 522 East Gray Street Louisville KY 40292 USA Department of Psychological and Brain Sciences University of Louisville Louisville KY 40292 USA Department of Anatomical Sciences and Neurobiology University of Louisville Louisville KY 40292 USA Department of Electrical Engineering IIT Kanpur India Department of Microbiology Immunology and Biochemistry University of Tennessee Health Science Center Memphis TN 38103 USA Center for Integrative and Translational Genomics University of Tennessee Health Science Center Memphis TN 38103 USA Department of Plant Pathology University of Kentucky Lexington KY 40546 USA UK Healthcare Genomics University of Kentucky Lexington KY 40536 USA Department of Entomology & Plant Pathology University of Tennessee Knoxville TN 37996 USA Department of Forestry University of Kentucky Lexington KY 40506 USA Department of Computer Science University of Kentucky Lexington KY 40506 USA Department of Computer Science University of Kentucky Lexington KY 40508 USA Department of Biological Sciences Eastern Kentucky University Richmond KY 40475 USA University of Tennessee Health Science Center – Oak-Ridge National Lab (UTHSC-ORNL) Center for Biomedical Informatics Department of Pediatrics Memphis TN 38103 USA Department of Molecular & Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Markey Cancer Center University of Kentucky Lexington KY 40536 USA Center for Environmental and Systems Biochemistry University of Kentucky Lexington KY 40536 USA Institute for Biomedical Informatics University of Kentucky Lexington KY 40536 USA Department of Molecular and Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Department of Statistics University of Kentucky Louisville KY

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Education for the future

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Science 2018年第6396期360卷 1409-1412页

作者： Cheung, Man Kit Schwendimann, Beat A. Ward, Adrian Pietrzak, Barbara Mollaoglu, Gurkan Duong, Michael Tran Allareddy, Veerasathpurush Ulltveit-Moe, Nils Dutton-Regester, Ken Zhang, Jian Scult, Matthew A. Singh, Poonam C. Yan, Hong Young Naz, Saima Isaacson, Kyle Dennis, Allison F. Beardsley, Felicia Rounds Al-Humaidan, Eyad Ibrahim Lo, Cody Jones, Tyler Sood, Prashant Nieuwenhuis, Rense Ali, Basant A. Yu, Kun-Hsing Arthur, Patrick Kobina Kumar, Brijesh Buschke, Falko Chen, Alexander Cingl, Lubomír O’Mullane, Anthony Peter Coetzee, Vinet Zaidi, Syed Shan-e-Ali Konstantinides, Nikos School of Life Sciences Chinese University of Hong Kong Shatin New Territories Hong Kong Graduate School of Education University of California Berkeley Berkeley 94720 CA United States University of Queensland St. Lucia 4072 QLD Australia Department of Hydrobiology Faculty of Biology Biological and Chemical Research Centre University of Warsaw Warsaw 02-089 Poland Department of Oncological Sciences University of Utah School of Medicine Salt Lake City 84112 UT United States Perelman School of Medicine University of Pennsylvania Philadelphia 19104 PA United States University of Illinois College of Dentistry Chicago 60612 IL United States Department of Information and Communication Technology University of Agder 4879 Grimstad Norway Department of Genetics and Computational Biology QIMR Berghofer Medical Research Institute Brisbane 4006 QLD Australia School of Safety and Environmental Engineering Hunan Institute of Technology Hengyang Hunan 421002 China Lahore 54000 Punjab Pakistan Department of Psychology and Neuroscience Duke University Durham 27708 NC United States National Museum of Marine Biology and Aquarium Chercheng Pingtung County 94450 Taiwan Division of Plant Microbe Interactions CSIR–National Botanical Research Institute Lucknow 226001 Uttar Pradesh India Program in Cell Molecular Developmental Biology and Biophysics (CMDB) Johns Hopkins University Baltimore 21218 MD United States Stem Cell and Tissue Re-Engineering Program King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia Department of Sociology and Anthropology University of La Verne La Verne 91750 CA United States Department of Bioengineering University of Utah Salt Lake City 84112 UT United States MRC Centre for Medical Mycology University of Aberdeen Aberdeen AB25 2ZD United Kingdom Faculty of Medicine University of British Columbia Vancouver V6T 1Z2 BC Canada School of Engineering Brown University Providence 02912 RI United States

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Metadata Correction: Importance-Performance Analysis of Personal Health Records in Taiwan: A Web-Based Survey

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Journal of medical Internet research 2017年第6期19卷 e209页

作者： Hsiao-Hsien Rau Yi-Syuan Wu Chi-Ming Chu Fu-Chung Wang Min-Huei Hsu Chi-Wen Chang Kang-Hua Chen Yen-Liang Lee Senyeong Kao Yu-Lung Chiu Hsyien-Chia Wen Anis Fuad Chien-Yeh Hsu Hung-Wen Chiu Graduate Institute of Biomedical Informatics Taipei Medical University Taipei Taiwan. Administration Department Healthconn Corp Taipei Taiwan. Institute of Medical Informatics Department of Computer Science of Information Engineering National Cheng Kung University Tainan Taiwan. School Of Public Health National Defense Medical Center Taiepi Taiwan. National Health Insurance Administration Ministry of Health and Welfare Taiepi Taiwan. School of Nursing College of Medicine Chang Gung University Linkou Taiwan. Division of Endocrinology Department of Pediatrics Linkou Chang Gung Memorial Hospital Linkou Taiwan. Internet of Things Laboratory Chunghwa Telecom Laboratories TaoYuen Taiwan. School of Health Care Administration Taipei Medical University Taipei Taiwan. Department of Biostatistics Epidemiology and Population Health Faculty of Medicine Universitas Gadjah Mada Yogyakarta Indonesia. Department of Information Management National Taipei University of Nursing and Health Sciences Taipei Taiwan. Master Program in Global Health and Development Taipei Medical University Taipei Taiwan.

[This corrects the article DOI: .].

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Adverse events following the first, second and third doses of a COVID-19 vaccine in hemodialysis patients

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Renal failure 2023年第1期45卷 2172432页

作者： Mei-Fen Pai Kuei-Ting Tung Shih-Ping Hsu Yu-Sen Peng Wan-Yu Lin Ju-Yeh Yang Hon-Yen Wu Yen-Ling Chiu Kai-Hsiang Shu Wan-Chuan Tsai Division of Nephrology Department of Internal Medicine Far Eastern Memorial Hospital New Taipei City Taiwan. Department of Internal Medicine National Taiwan University Hospital and College of Medicine Taipei City Taiwan. School of Life Science National Taiwan Normal University Taipei City Taiwan. Department of Applied Cosmetology Lee-Ming Institute of Technology New Taipei City Taiwan. Department of Electrical Engineering Yuan Ze University Taoyuan City Taiwan. Institute of Epidemiology and Preventive Medicine College of Public Health National Taiwan University Taipei City Taiwan. Center for General Education Lee-Ming Institute of Technology New Taipei City Taiwan. Faculty of Medicine School of Medicine National Yang-Ming University Taipei City Taiwan. Graduate Program in Biomedical Informatics Yuan Ze University Taoyuan City Taiwan.

BACKGROUND:This study aimed to identify adverse events following the first three doses of COVID-19 vaccines in hemodialysis (HD) patients. Risk factors associated with postvaccination adverse events were explored. METHODS:Postvaccination adverse events in 438 HD patients who received 3 doses of COVID-19 vaccines were prospectively assessed. The adverse events among three doses were compared using generalized linear mixed models. Factors associated with adverse events were assessed with multivariate analyses. RESULTS:The vast majority of participants received Oxford/AstraZeneca ChAdOx1 as their first two doses and Moderna mRNA-1273 as their third dose. Overall, 79%, 50% and 84% of the participants experienced at least one adverse event after their first, second, and third doses, respectively. These adverse events were mostly minor, short-lived and less than 5% reported daily activities being affected. Compared with the first dose, the second dose caused a lower rate of adverse events. Compared with the first dose, the third dose elicited a higher rate of injection site reactions and a lower rate of systemic reactions. Multivariate analyses showed that every 10-year increase of age (odds ratio 0.67, 95% confidence intervals 0.57-0.79) was associated with decreased risk of adverse events, while female sex (2.82, 1.90-4.18) and arteriovenous fistula (1.73, 1.05-2.84) were associated with increased risk of adverse events. Compared with Oxford/AstraZeneca ChAdOx1, Moderna mRNA-1273 was associated with an increased risk of injection site reactions. CONCLUSIONS:COVID-19 vaccination was well tolerated in HD patients. Age, sex, dialysis vascular access and vaccine types were associated with postvaccination adverse events.

关键词： COVID-19 ChAdOx1 Hemodialysis adverse event mRNA-1273 vaccination

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Correction: A COVID-19 Pandemic Artificial Intelligence-Based System With Deep Learning Forecasting and Automatic Statistical Data Acquisition: Development and Implementation Study

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Journal of medical Internet research 2021年第7期23卷 e31085页

作者： Cheng-Sheng Yu Shy-Shin Chang Tzu-Hao Chang Jenny L Wu Yu-Jiun Lin Hsiung-Fei Chien Ray-Jade Chen Department of Family Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Family Medicine Taipei Medical University Hospital Taipei Taiwan. Graduate Institute of Biomedical Informatics College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Professional Master Program in Artificial Intelligence in Medicine College of Medicine Taipei Medical University Taipei Taiwan. Clinical Big Data Research Center Taipei Medical University Hospital Taipei Taiwan. Division of Plastic Surgery Department of Surgery Taipei Medical University Hospital and School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Surgery School of Medicine College of Medicine Taipei Medical University Taipei Taiwan. Division of General Surgery Department of Surgery Taipei Medical University Hospital Taipei Taiwan.

[This corrects the article DOI: 10.2196/27806.].

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Author Correction: Cellular deconvolution of GTEx tissues powers discovery of disease and cell-type associated regulatory variants

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Nature communications 2020年第1期11卷 4426页

作者： Margaret K R Donovan Agnieszka D'Antonio-Chronowska Matteo D'Antonio Kelly A Frazer 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 Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. madantonio@health.ucsd.edu. Department of Pediatrics and Rady Children's Hospital University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu. Institute for Genomic Medicine University of California San Diego La Jolla CA 92093 USA. kafrazer@health.ucsd.edu.

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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25th Annual Computational Neuroscience Meeting CNS-2016, Seogwipo City, South Korea, July 2-7, 2016 Abstracts

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BMC NEUROSCIENCE 2016年第1期17卷 1-112页

作者： [Anonymous] Computational Neurobiology Laboratory The Salk Institute for Biological Studies San Diego USA UNIC CNRS Gif sur Yvette France The European Institute for Theoretical Neuroscience (EITN) Paris France ATR Computational Neuroscience Laboratories Kyoto Japan Krembil Research Institute University Health Network Toronto Canada Department of Physiology University of Toronto Toronto Canada Department of Medicine (Neurology) University of Toronto Toronto Canada Department of Physics University of New Hampshire Durham USA Department of Neurophysiology Nencki Institute of Experimental Biology Warsaw Poland Department of Theory Wigner Research Centre for Physics of the Hungarian Academy of Sciences Budapest Hungary Department of Mathematical Sciences KAIST Daejoen Republic of Korea Department of Mathematics University of Houston Houston USA Department of Biochemistry & Cell Biology and Institute of Biosciences and Bioengineering Rice University Houston USA Department of Biology and Biochemistry University of Houston Houston USA Grupo de Neurocomputación Biológica Dpto. de Ingeniería Informática Escuela Politécnica Superior Universidad Autónoma de Madrid Madrid Spain Department of Biological Sciences University of Southern California Los Angeles USA Center for Neuroscience Korea Institute of Science and Technology Seoul South Korea Department of Neurology Albert Einstein College of Medicine Bronx USA Center for Neuroscience KIST Seoul South Korea Department of Neuroscience University of Science and Technology Daejon South Korea Systems Neuroscience Group QIMR Berghofer Medical Research Institute Herston Australia Department of Psychology Yonsei University Seoul South Korea Department of Psychiatry Kyung Hee University Hospital at Gangdong Seoul South Korea Department of Psychiatry Veterans Administration Boston Healthcare System and Harvard Medical School Brockton USA Department of Electrical and Electronic Engineering The University of Melbourne Parkvil

A1 Functional advantages of cell-type heterogeneity in neural circuits Tatyana O. Sharpee A2 Mesoscopic modeling of propagating waves in visual cortex Alain Destexhe A3 Dynamics and biomarkers of mental disorders Mitsuo Kawato F1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneurons Vladislav Sekulić, Frances K. Skinner F2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brains Daniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán Somogyvári F3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks. Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir Josić O1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generators Irene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo Varona O2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrain Eunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun Choi O3 Modeling auditory stream segregation, build-up and bistability James Rankin, Pamela Osborn Popp, John Rinzel O4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fields Alejandro Tabas, André Rupp, Emili Balaguer-Ballester O5 A simple model of retinal response to multi-electrode stimulation Matias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish Meffin O6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination task Veronika Koren, Timm Lochmann, Valentin Dragoi, Klaus Obermayer O7 Input-location dependent gain modulation in cerebellar nucleus neurons Maria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Ni

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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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Polygenic risk modeling for prediction of epithelial ovarian cancer risk (vol 30, pg 349, 2021)

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EUROPEAN JOURNAL OF HUMAN GENETICS 2022年第5期30卷 630-631页

作者： Dareng, Eileen O. Tyrer, Jonathan P. Barnes, Daniel R. Jones, Michelle R. Yang, Xin Aben, Katja K. H. Adank, Muriel A. Agata, Simona Andrulis, Irene L. Anton-Culver, Hoda Antonenkova, Natalia N. Aravantinos, Gerasimos Arun, Banu K. Augustinsson, Annelie Balmana, Judith Bandera, Elisa V. Barkardottir, Rosa B. Barrowdale, Daniel Beckmann, Matthias W. Beeghly-Fadiel, Alicia Benitez, Javier Bermisheva, Marina Bernardini, Marcus Q. Bjorge, Line Black, Amanda Bogdanova, Natalia V. Bonanni, Bernardo Borg, Ake Brenton, James D. Budzilowska, Agnieszka Butzow, Ralf Buys, Saundra S. Cai, Hui Caligo, Maria A. Campbell, Ian Cannioto, Rikki Cassingham, Hayley Chang-Claude, Jenny Chanock, Stephen J. Chen, Kexin Chiew, Yoke-Eng Chung, Wendy K. Claes, Kathleen B. M. Colonna, Sarah Cook, Linda S. Couch, Fergus J. Daly, Mary B. Dao, Fanny Davies, Eleanor de la Hoya, Miguel de Putter, Robin Dennis, Joe DePersia, Allison Devilee, Peter Diez, Orland Ding, Yuan Chun Doherty, Jennifer A. Domchek, Susan M. Dork, Thilo du Bois, Andreas Durst, Matthias Eccles, Diana M. Eliassen, Heather A. Engel, Christoph Evans, Gareth D. Fasching, Peter A. Flanagan, James M. Fortner, Renee T. Machackova, Eva Friedman, Eitan Ganz, Patricia A. Garber, Judy Gensini, Francesca Giles, Graham G. Glendon, Gord Godwin, Andrew K. Goodman, Marc T. Greene, Mark H. Gronwald, Jacek Hahnen, Eric Haiman, Christopher A. Hakansson, Niclas Hamann, Ute Hansen, Thomas V. O. Harris, Holly R. Hartman, Mikael Heitz, Florian Hildebrandt, Michelle A. T. Hogdall, Estrid Hogdall, Claus K. Hopper, John L. Huang, Ruea-Yea Huff, Chad Hulick, Peter J. Huntsman, David G. Imyanitov, Evgeny N. Isaacs, Claudine Jakubowska, Anna James, Paul A. Janavicius, Ramunas Jensen, Allan Johannsson, Oskar Th. John, Esther M. Jones, Michael E. Kang, Daehee Karlan, Beth Y. Karnezis, Anthony Kelemen, Linda E. Khusnutdinova, Elza Kiemeney, Lambertus A. Kim, Byoung-Gie Kjaer, Susanne K. Komenaka, Ian Kupryjanczyk, Jolanta Kurian, Allison W. Kwong, Ava Lambrechts, Diether Larson, Melissa C. Lazaro, Conxi L University of Cambridge Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Cambridge UK University of Cambridge Centre for Cancer Genetic Epidemiology Department of Oncology Cambridge UK Center for Bioinformatics and Functional Genomics Cedars-Sinai Medical Center Los Angeles CA USA Radboud University Medical Center Radboud Institute for Health Sciences Nijmegen The Netherlands Netherlands Comprehensive Cancer Organisation Utrecht The Netherlands The Netherlands Cancer Institute—Antoni van Leeuwenhoek hospital Family Cancer Clinic Amsterdam The Netherlands Veneto Institute of Oncology IOV—IRCCS Immunology and Molecular Oncology Unit Padua Italy Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital Fred A. Litwin Center for Cancer Genetics Toronto ON Canada University of Toronto Department of Molecular Genetics Toronto ON Canada University of California Irvine Department of Epidemiology Genetic Epidemiology Research Institute Irvine CA USA N.N. Alexandrov Research Institute of Oncology and Medical Radiology Minsk Belarus ‘Agii Anargiri’ Cancer Hospital Athens Greece University of Texas MD Anderson Cancer Center Department of Breast Medical Oncology Houston TX USA Lund University Department of Cancer Epidemiology Clinical Sciences Lund Sweden Vall d’Hebron Institute of Oncology Hereditary cancer Genetics Group Barcelona Spain University Hospital of Vall d’Hebron Department of Medical Oncology Barcelona Spain Rutgers Cancer Institute of New Jersey Cancer Prevention and Control Program New Brunswick NJ USA Landspitali University Hospital Department of Pathology Reykjavik Iceland University of Iceland BMC (Biomedical Centre) Faculty of Medicine Reykjavik Iceland University Hospital Erlangen Friedrich-Alexander-University Erlangen-Nuremberg Department of Gynecology and Obstetrics Comprehensive Cancer Center ER-EMN Erlangen Germany Vanderbilt University School of Medicine Division of Epidemiology Department

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

关键词： Clinical genetics Genetic markers Risk factors Biomedicine general Human Genetics Bioinformatics Gene Expression Cytogenetics

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