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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy

arXiv

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arXiv 2021年

作者： Nelson, Glyn Boehm, Ulrike Bagley, Steve Bajcsy, Peter Bischof, Johanna Brown, Claire M. Dauphin, Aurélien Dobbie, Ian M. Eriksson, John E. Faklaris, Orestis Fernandez-Rodriguez, Julia Ferrand, Alexia Gelman, Laurent Gheisari, Ali Hartmann, Hella Kukat, Christian Laude, Alex Mitkovski, Miso Munck, Sebastian North, Alison J. Rasse, Tobias M. Resch-Genger, Ute Schuetz, Lucas C. Seitz, Arne Strambio-De-Castillia, Caterina Swedlow, Jason R. Alexopoulos, Ioannis Aumayr, Karin Avilov, Sergiy Bakker, Gert-Jan Bammann, Rodrigo R. Bassi, Andrea Beckert, Hannes Beer, Sebastian Belyaev, Yury Bierwagen, Jakob Birngruber, Konstantin A. Bosch, Manel Breitlow, Juergen Cameron, Lisa A. Chalfoun, Joe Chambers, James J. Chen, Chieh-Li Conde-Sousa, Eduardo Corbett, Alexander D. Cordelieres, Fabrice P. Nery, Elaine Del Dietzel, Ralf Eismann, Frank Fazeli, Elnaz Felscher, Andreas Fried, Hans Gaudreault, Nathalie Goh, Wah Ing Guilbert, Thomas Hadleigh, Roland Hemmerich, Peter Holst, Gerhard A. Itano, Michelle S. Jaffe, Claudia B. Jambor, Helena K. Jarvis, Stuart C. Keppler, Antje Kirchenbuechler, David Kirchner, Marcel Kobayashi, Norio Krens, Gabriel Kunis, Susanne Lacoste, Judith Marcello, Marco Martins, Gabriel G. Metcalf, Daniel J. Mitchell, Claire A. Moore, Joshua Mueller, Tobias Nelson, Michael S. Ogg, Stephen Onami, Shuichi Palmer, Alexandra L. Paul-Gilloteaux, Perrine Pimentel, Jaime A. Plantard, Laure Podder, Santosh Rexhepaj, Elton Royon, Arnaud Saari, Markku A. Schapman, Damien Schoonderwoert, Vincent Schroth-Diez, Britta Schwartz, Stanley Shaw, Michael Spitaler, Martin Stoeckl, Martin T. Sudar, Damir Teillon, Jeremie Terjung, Stefan Thuenauer, Roland Wilms, Christian D. Wright, Graham D. Nitschke, Roland Bioimaging Unit Newcastle University Newcastle upon TyneNE4 5PL United Kingdom Janelia Research Campus Howard Hughes Medical Institute AshburnVA20147 United States Visualisation Irradiation & Analysis Cancer Research UK Manchester Institute Alderley Park Macclesfield United Kingdom National Institute of Standards and Technology GaithersburgMD20899 United States Euro-BioImaging Heidelberg69117 Germany McGill University MontrealQCH3G 0B1 Canada Unité Génétique et Biologie du Développement U934 PICT-IBiSA Institut Curie/Inserm CNRS PSL Research University Paris75005 France Department of Biochemistry University of Oxford Oxford OxonOX1 3QU United Kingdom Turku Bioscience Centre Euro-Bioimaging ERIC Turku20520 Finland Biocampus CNRS UAR 3426 Montpellier34293 France Centre for Cellular Imaging Sahlgrenska Academy University of Gothenburg Gothenburg40530 Sweden Imaging Core Facility Biozentrum University of Basel Basel4056 Switzerland Friedrich Miescher Institute for Biomedical Research Basel4058 Switzerland Light Microscopy Facility CMCB Technology Platform TU Dresden Dresden01307 Germany FACS & Imaging Core Facility Max Planck Institute for Biology of Ageing Cologne50931 Germany Light Microscopy Facility Max Planck Institute of Experimental Medicine Goettingen37075 Germany VIB BioImaging Core VIB-KU Leuven Center for Brain and Disease Research KU Leuven Department for Neuroscience Flanders Leuven3000 Belgium The Rockefeller University New YorkNY10065 United States Scientific Service Group Microscopy Max Planck Institute for Heart and Lung Research Bad Nauheim61231 Germany Division Biophotonics Federal Institute for Materials Research and Testing Berlin12489 Germany European Molecular Biology Laboratory Advanced Light Microscopy Facility Heidelberg69117 Germany Faculty of Life Sciences Ecole Polytechnique Fédérale de Lausanne Vaud Lausanne1015 Switzerland Program in Molecular Medicine University of Massachusetts Medica

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated, quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist’s experiments, while more than half have even failed to reproduce their own experiments1. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique2. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g., DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE3), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility4. In April 2020, the QUality Assessment and REProducibility for Instruments and Images in Light Microscopy (QUAREP-LiMi) initiative5 was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved qualit

关键词： DNA sequences

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Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis

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四川生理科学杂志 2020年第4期42卷 480-480页

作者： Carol C L Chen Department of Human Genetics McGill University Montreal QC H3A 0C7 Canada Division of Experimental Medicine Department of Medicine McGill University Montreal QC H4A 3J1 Canada Quantitative Life Sciences McGill University Montreal QC H3A 2A7 Canada Lady Davis Research Institute Jewish General Hospital Montreal QC H3T 1E2 Canada Department of Pediatrics McGill University and The Research Institute of the McGill University Health Centre Montreal QC H4A 3J1 Canada Canadian Centre for Computational Genomics McGill University Montreal QC H3A 0E9 Canada Developmental and Stem Cell Biology Program The Hospital for Sick Children Toronto ON M5G 0A4 Canada The Arthur and Sonia Labatt Brain Tumour Research Centre The Hospital for Sick Children Toronto ON M5G 0A4 Canada Department of Oncology and The Milner Institute Jeffrey Cheah Biomedical Centre University of Cambridge Cambridge CB2 0AW UK CRUK Children’s Brain Tumour Centre of Excellence University of Cambridge Cambridge CB2 0RE UK Nuclear Function in CNS Pathophysiology German Center for Neurodegenerative Diseases (DZNE) Bonn 53127 Germany Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Boston MA 02215 USA Department of Pathology Montreal Neurological Institute McGill University Montreal QC H3A 2B4 Canada Department of Pathology Montreal Children’s Hospital McGill University Health Centre Montreal QC H4A 3J1 Canada UCL Queen Square Institute of Neurology London WC1N 3BG UK Department of Biochemistry and Biophysics and Penn Epigenetics Institute Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104-6073 USA Department of Biochemistry McGill University Montreal QC H3A 1A3 Canada Second Department of Paediatrics Semmelweis University Budapest 1094 Hungary Department of Neurosurgery University of Debrecen Debrecen 4032 Hungary Department of Oncology Faculty of Medicine University of Debrecen Debrecen 4032 Hungary Department of Paediatric Haematology and Oncol

Histone H3.3 glycine 34 to arginine/valine(G34R/V)mutations drive deadly gliomas and show exquisite regional and temporal specificity,suggesting a developmental context permissive to their *** we show that 50%of G34R/V tumors(n=95)bear activating PDGFRA mutations that display strong selection pressure at *** considered gliomas,G34R/V tumors actually arise in GSX2/DLX-expressing interneuron progenitors,where G34R/V mutations impair neuronal *** lineage of origin may facilitate PDGFRA co-option through a chromatin loop connecting PDGFRA to GSX2 regulatory elements,promoting PDGFRA overexpression and *** the single-cell level,G34R/V tumors harbor dual neuronal/astroglial identity and lack oligodendroglial programs,actively repressed by GSX2/DLX-mediated cell fate specification.G34R/V may become dispensable for tumor maintenance,whereas mutant-PDGFRA is potently ***,our results open novel research avenues in deadly tumors.G34R/V gliomas are neuronal malignancies where interneuron progenitors are stalled in differentiation by G34R/V mutations and malignant gliogenesis is promoted by co-option of a potentially targetable pathway,PDGFRA signaling.

关键词： PDGFRA specificity connecting

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Evolution at the edge of expanding populations

arXiv

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arXiv 2017年

作者： Deforet, Maxime Carmona-Fontaine, Carlos Korolev, Kirill S. Xavier, Joao B. Sorbonne Université Centre National de la Recherche Rcientifique Laboratoire Jean Perrin LJP Paris75005 France Center for Genomics and Systems Biology Department of Biology New York University New York CityNY10003 United States Department of Physics Graduate Program in Bioinformatics Boston University BostonMA02215 Program in Computational Biology Memorial Sloan-Kettering Cancer Center New York CityNY10065 United States

Predicting evolution of expanding populations is critical to control biological threats such as invasive species and cancer metastasis. Expansion is primarily driven by reproduction and dispersal, but nature abounds with examples of evolution where organisms pay a reproductive cost to disperse faster. When does selection favor this 'survival of the fastest?' We searched for a simple rule, motivated by evolution experiments where swarming bacteria evolved into an hyperswarmer mutant which disperses ∼ 100% faster but pays a growth cost of ∼ 10% to make many copies of its flagellum. We analyzed a two-species model based on the Fisher equation to explain this observation: the population expansion rate (v) results from an interplay of growth (r) and dispersal (D) and is independent of the carrying capacity: v = 2 √rD. A mutant can take over the edge only if its expansion rate (v2) exceeds the expansion rate of the established species' (v1);this simple condition (v2> v1) determines the maximum cost in slower growth that a faster mutant can pay and still be able to take over. Numerical simulations and time-course experiments where we tracked evolution by imaging bacteria suggest that our findings are general: less favorable conditions delay but do not entirely prevent the success of the fastest. Thus, the expansion rate defines a traveling wave fitness, which could be combined with trade-offs to predict evolution of expanding populations. Copyright © 2017, The Authors. All rights reserved.

关键词： Bacteria

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Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors (vol 19, pg 302, 2018)

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NATURE IMMUNOLOGY 2018年第6期19卷 645-645页

作者： Patin, Etienne Hasan, Milena Bergstedt, Jacob Rouilly, Vincent Libri, Valentina Urrutia, Alejandra Alanio, Cecile Scepanovic, Petar Hammer, Christian Joensson, Friederike Beitz, Benoit Quach, Helene Lim, Yoong Wearn Hunkapiller, Julie Zepeda, Magge Green, Cherie Piasecka, Barbara Leloup, Claire Rogge, Lars Huetz, Francois Peguillet, Isabelle Lantz, Olivier Fontes, Magnus Di Santo, James P. Thomas, Stephanie Fellay, Jacques Duffy, Darragh Quintana-Murci, Lluis Albert, Matthew L. Unit of Human Evolutionary Genetics Department of Genomes & Genetics Institut Pasteur Paris France CNRS UMR 2000 Paris France Center of Bioinformatics Biostatistics and Integrative Biology Institut Pasteur Paris France Center for Translation Research Institut Pasteur Paris France Department of Automatic Control Lund University Lund Sweden International Group for Data Analysis Institut Pasteur Paris France Laboratory of Dendritic Cell Immunobiology Department of Immunology Institut Pasteur Paris France INSERM U1223 Paris France Department of Cancer Immunology Genentech South San Francisco CA USA School of Life Sciences École Polytechnique Fédérale de Lausanne Lausanne Switzerland Swiss Institute of Bioinformatics Lausanne Switzerland Antibodies in Therapy and Pathology Department of Immunology Institut Pasteur Paris France INSERM U760 Paris France Department of Human Genetics Genentech South San Francisco CA USA Employee Donation Program Genentech South San Francisco CA USA Department of Development Sciences Genentech South San Francisco CA USA Immunoregulation Unit Department of Immunology Institut Pasteur Paris France INSERM U783 Faculté de Médecine Site Necker-Enfants Malades Université Paris Descartes Paris France Lymphocyte Population Biology CNRS URA 1961 Institut Pasteur Paris France Center of Clinical Investigations CIC-BT1428 IGR/Curie Paris France Department of Biopathology Institut Curie Paris France Equipe Labellisée de la Ligue de Lutte Contre le Cancer Institut Curie Paris France INSERM/Institut Curie U932 Paris France Centre for Mathematical Sciences Lund University Lund Sweden Innate Immunity Unit Institut Pasteur Paris France St. Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch Rockefeller University New York NY USA Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France Paris Descartes University Imagine Insti

The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.

关键词： Activated Lymphocyte Genetic factors Immunity Nonspecific Immune Cell Variation

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The Functional Genomic Circuitry of Human Glioblastoma Stem Cells

SSRN

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SSRN 2018年

作者： MacLeod, Graham Bozek, Danielle A. Rajakulendran, Nishani Monteiro, Vernon Ahmadi, Moloud Steinhart, Zachary Kushida, Michelle M. Yu, Helen Coutinho, Fiona J. Restall, Ian Hao, Xiaoguang Hart, Traver Luchman, H. Artee Weiss, Samuel Dirks, Peter B. Angers, Stephane Leslie Dan Faculty of Pharmacy University of Toronto ONM5S 3M2 Canada Hotchkiss Brain Institute Department of Cell Biology and Anatomy Cumming School of Medicine University of Calgary CalgaryABT2N 4N1 Canada Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain Tumour Research Centre The Hospital for Sick Children TorontoONM5G 0A4 Canada Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center HoustonTX77030 United States Department of Molecular Genetics Department of Laboratory Medicine and Pathobiology Division of Neurosurgery Department of Surgery University of Toronto ON Canada Division of Neurosurgery The Hospital for Sick Children TorontoONM5G 0A4 Canada Department of Biochemistry Faculty of Medicine University of Toronto ONM5G 0A4 Canada

Successful glioblastoma (GBM) therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patientderived GBM stem cells to interrogate function of the coding genome, we identify diverse actionable pathways responsible for growth that reveal the gene-essential circuitry of GBM stemness. In particular, we describe the Sox developmental transcription factor family;H3K79 methylation by DOT1L;and ufmylation stress responsiveness programs as essential for GBM stemness. Additionally, we find mechanisms of temozolomide resistance and sensitivity that could lead to combination strategies with this standard of care treatment. By reaching beyond static genome analysis of bulk tumors, with a genome wide functional approach, we dive deep into a broad range of biological processes to provide new understanding of GBM growth and treatment resistance. © 2018, The Authors. All rights reserved.

关键词： Stem cells

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Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci (vol 50, pg 928, 2018)

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NATURE genetics 2019年第2期51卷 363-363页

作者： Schumacher, Fredrick R. Al Olama, Ali Amin Berndt, Sonja I. Benlloch, Sara Ahmed, Mahbubl Saunders, Edward J. Dadaev, Tokhir Leongamornlert, Daniel Anokian, Ezequiel Cieza-Borrella, Clara Goh, Chee Brook, Mark N. Sheng, Xin Fachal, Laura Dennis, Joe Tyrer, Jonathan Muir, Kenneth Lophatananon, Artitaya Stevens, Victoria L. Gapstur, Susan M. Carter, Brian D. Tangen, Catherine M. Goodman, Phyllis J. Thompson, Ian M., Jr. Batra, Jyotsna Chambers, Suzanne Moya, Leire Clements, Judith Horvath, Lisa Tilley, Wayne Risbridger, Gail P. Gronberg, Henrik Aly, Markus Nordstrom, Tobias Pharoah, Paul Pashayan, Nora Schleutker, Johanna Tammela, Teuvo L. J. Sipeky, Csilla Auvinen, Anssi Albanes, Demetrius Weinstein, Stephanie Wolk, Alicja Hakansson, Niclas West, Catharine M. L. Dunning, Alison M. Burnet, Neil Mucci, Lorelei A. Giovannucci, Edward Andriole, Gerald L. Cussenot, Olivier Cancel-Tassin, Geraldine Koutros, Stella Freeman, Laura E. Beane Sorensen, Karina Dalsgaard Orntoft, Torben Falck Borre, Michael Maehle, Lovise Grindedal, Eli Marie Neal, David E. Donovan, Jenny L. Hamdy, Freddie C. Martin, Richard M. Travis, Ruth C. Key, Tim J. Hamilton, Robert J. Fleshner, Neil E. Finelli, Antonio Ingles, Sue Ann Stern, Mariana C. Rosenstein, Barry S. Kerns, Sarah L. Ostrer, Harry Lu, Yong-Jie Zhang, Hong-Wei Feng, Ninghan Mao, Xueying Guo, Xin Wang, Guomin Sun, Zan Giles, Graham G. Southey, Melissa C. MacInnis, Robert J. FitzGerald, Liesel M. Kibel, Adam S. Drake, Bettina F. Vega, Ana Gomez-Caamano, Antonio Szulkin, Robert Eklund, Martin Kogevinas, Manolis Llorca, Javier Castano-Vinyals, Gemma Penney, Kathryn L. Stampfer, Meir Park, Jong Y. Sellers, Thomas A. Lin, Hui-Yi Stanford, Janet L. Cybulski, Cezary Wokolorczyk, Dominika Lubinski, Jan Ostrander, Elaine A. Geybels, Milan S. Nordestgaard, Borge G. Nielsen, Sune F. Weischer, Maren Bisbjerg, Rasmus Roder, Martin Andreas Iversen, Peter Brenner, Hermann Cuk, Katarina Holleczek, Bernd Maier, Christiane Luedeke, Manuel Schnoeller, Thomas Kim, Jeri Logothetis, Christopher J. John, E Department of Population and Quantitative Health Sciences Case Western Reserve University Cleveland USA Seidman Cancer Center University Hospitals Cleveland USA Royal Marsden NHS Foundation Trust London UK Department of Public Health and Primary Care Centre for Cancer Genetic Epidemiology University of Cambridge Strangeways Research Laboratory Cambridge UK Department of Clinical Neurosciences University of Cambridge Cambridge UK Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Bethesda USA Institute of Cancer Research London UK Department of Preventive Medicine Keck School of Medicine University of Southern California/Norris Comprehensive Cancer Center Los Angeles USA Fundación Pública Galega de Medicina Xenómica–SERGAS Grupo de Medicina Xenómica CIBERER IDIS Santiago de Compostela Spain Department of Oncology Centre for Cancer Genetic Epidemiology Strangeways Laboratory University of Cambridge Cambridge UK Division of Population Health Health Services Research and Primary Care University of Manchester Manchester UK Warwick Medical School University of Warwick Coventry UK Epidemiology Research Program American Cancer Society Atlanta USA SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle USA CHRISTUS Santa Rosa Hospital–Medical Center San Antonio USA Institute of Health and Biomedical Innovation and School of Biomedical Sciences Queensland University of Technology Brisbane Australia Australian Prostate Cancer Research Centre–Qld Translational Research Institute Brisbane Australia Menzies Health Institute of Queensland Griffith University Nathan Australia Cancer Council Queensland Fortitude Valley Australia Chris O’Brien Lifehouse (COBLH) Camperdown Australia Garvan Institute of Medical Research Sydney Australia Dame Roma Mitchell Cancer Research Centre University of Adelaide Adelaide Australia Monash Biomedicine Discovery Institute Cancer Program Prostate Cancer Research Program Department of Anatom

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.

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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk (vol 51, pg 659, 2019)

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NATURE genetics 2019年第6期51卷 1068-1068页

作者： Huckins, Laura M. Dobbyn, Amanda Ruderfer, Douglas M. Hoffman, Gabriel Wang, Weiqing Pardinas, Antonio F. Rajagopal, Veera M. Als, Thomas D. Nguyen, Hoang T. Girdhar, Kiran Boocock, James Roussos, Panos Fromer, Menachem Kramer, Robin Domenici, Enrico Gamazon, Eric R. Purcell, Shaun Demontis, Ditte Borglum, Anders D. Walters, James T. R. O'Donovan, Michael C. Sullivan, Patrick Owen, Michael J. Devlin, Bernie Sieberts, Solveig K. Cox, Nancy J. Im, Hae Kyung Sklar, Pamela Stahl, Eli A. Pamela Sklar Division of Psychiatric Genomics Icahn School of Medicine at Mount Sinai New York NY USA Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai New York NY USA Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai New York NY USA Vanderbilt University Medical Center Nashville TN USA MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University Cardiff UK Department of Biomedicine Aarhus University Aarhus Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH Denmark Center for Integrative Sequencing Aarhus University Aarhus Denmark Department of Human Genetics David Geffen School of Medicine University of California Los Angeles Los Angeles CA USA Human Brain Collection Core National Institute of Mental Health Bethesda MD USA Laboratory of Neurogenomic Biomarkers Centre for Integrative Biology (CIBIO) University of Trento Trento Italy Clare Hall University of Cambridge Cambridge UK University of North Carolina at Chapel Hill Chapel Hill NC USA Karolinska Institutet Stockholm Sweden Department of Psychiatry University of Pittsburgh Pittsburgh PA USA Systems Biology Sage Bionetworks Seattle WA USA Section of Genetic Medicine Department of Medicine University of Chicago Chicago IL USA Integrated Technology Research Laboratories Pharmaceutical Research Division Takeda Pharmaceutical Company Limited Fujisawa Japan Neuropsychiatry Section Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Neuropsychiatric Signaling Program Department of Psychiatry Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Psychiatry JJ Peters Virginia Medical Center Bronx NY USA Department of Neuroscience Icahn School of Medicine at Mount Sinai New York New York NY USA Friedman Brain Institute

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

关键词： Gene expression Genome-wide association studies Schizophrenia Transcriptomics

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Effect of climate on traits of dominant and rare tree species in the world's forests

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Nature communications 2025年第1期16卷 4773页

作者： Iris Hordijk Lourens Poorter Jingjing Liang Peter B Reich Sergio de-Miguel Gert-Jan Nabuurs Javier G P Gamarra Han Y H Chen Mo Zhou Susan K Wiser Hans Pretzsch Alain Paquette Nicolas Picard Bruno Hérault Jean-Francois Bastin Giorgio Alberti Meinrad Abegg Yves C Adou Yao Angelica M Almeyda Zambrano Braulio V Alvarado Esteban Alvarez-Davila Patricia Alvarez-Loayza Luciana F Alves Iêda Amaral Christian Ammer Clara Antón-Fernández Alejandro Araujo-Murakami Luzmila Arroyo Valerio Avitabile Gerardo A Aymard C Timothy Baker Olaf Banki Jorcely Barroso Meredith L Bastian Luca Birigazzi Philippe Birnbaum Robert Bitariho Pascal Boeckx Frans Bongers Olivier Bouriaud Pedro H S Brancalion Susanne Brandl Francis Q Brearley Roel Brienen Eben N Broadbent Helge Bruelheide Roberto Cazzolla Gatti Ricardo G Cesar Goran Cesljar Robin L Chazdon Chelsea Chisholm Emil Cienciala Connie J Clark David B Clark Gabriel Colletta David Coomes Fernando Cornejo Valverde Jose J Corral-Rivas Philip Crim Jonathan Cumming Selvadurai Dayanandan André L de Gasper Mathieu Decuyper Géraldine Derroire Ben DeVries Ilija Djordjevic Aurélie Dourdain Jiri Dolezal Nestor Laurier Engone Obiang Brian Enquist Teresa Eyre Adandé Belarmain Fandohan Tom M Fayle Leandro V Ferreira Ted R Feldpausch Leena Finér Markus Fischer Christine Fletcher Lorenzo Frizzera Damiano Gianelle Henry B Glick David Harris Andrew Hector Andreas Hemp John Herbohn Annika Hillers Eurídice N Honorio Coronado Cang Hui Hyunkook Cho Thomas Ibanez Ilbin Jung Nobuo Imai Andrzej M Jagodzinski Bogdan Jaroszewicz Vivian Johannsen Carlos A Joly Tommaso Jucker Viktor Karminov Kuswata Kartawinata Elizabeth Kearsley David Kenfack Deborah Kennard Sebastian Kepfer-Rojas Gunnar Keppel Mohammed Latif Khan Timothy Killeen Hyun Seok Kim Kanehiro Kitayama Michael Köhl Henn Korjus Florian Kraxner Diana Laarmann Mait Lang Simon Lewis Huicui Lu Natalia Lukina Brian Maitner Yadvinder Malhi Eric Marcon Beatriz Schwantes Marimon Ben Hur Marimon-Junior Andrew Robert Marshall Emanuel Martin Olga Martynenko Jorge A Mea Institute of Integrative Biology ETH Zurich (Swiss Federal Institute of Technology) Zurich Switzerland. irishordijk@***. Wageningen University and Research Wageningen The Netherlands. irishordijk@***. Wageningen University and Research Wageningen The Netherlands. Department of Forestry and Natural Resources Purdue University West Lafayette IN USA. Department of Forest Resources University of Minnesota St Paul MN USA. Hawkesbury Institute for the Environment Western Sydney University Penrith NSW Australia. Department of Agricultural and Forest Sciences and Engineering University of Lleida Lleida Spain. Forest Science and Technology Centre of Catalonia (CTFC) Solsona Spain. Forestry Division Food and Agriculture Organization of the United Nations Rome Italy. Faculty of Natural Resources Management Lakehead University Thunder Bay ON Canada. Manaaki Whenua-Landcare Research Lincoln New Zealand. Chair for Forest Growth and Yield Science TUM School for Life Sciences Technical University of Munich Munich Germany. Centre for Forest Research Université du Québec à Montréal Montréal QC Canada. GIP ECOFOR Paris France. CIRAD Forêts et Sociétés Montpellier France. Forêts et Sociétés Univ Montpellier CIRAD Montpellier France. Gembloux Agro Bio-Tech University of Liege Liege Belgium. Faculty of Science and Technology Free University of Bolzano Bolzano Italy. Department of Agricultural Food Environmental and Animal Sciences University of Udine Udine Italy. Swiss Federal Institute for Forest Snow and Landscape Research WSL Birmensdorf Switzerland. UFR Biosciences University Félix Houphouët-Boigny Abidjan Côte d'Ivoire. Spatial Ecology and Conservation Laboratory Center for Latin American Studies University of Florida Gainesville FL USA. Forestry School Tecnológico de Costa Rica TEC Cartago Costa Rica. Fundacion ConVida Universidad Nacional Abierta y a Distancia UNAD Medellin Colombia. Field Museum of Natural History Chicago IL USA. Center for Trop

Species' traits and environmental conditions determine the abundance of tree species across the globe. The extent to which traits of dominant and rare tree species differ remains untested across a broad environmental range, limiting our understanding of how species traits and the environment shape forest functional composition. We use a global dataset of tree composition of >22,000 forest plots and 11 traits of 1663 tree species to ask how locally dominant and rare species differ in their trait values, and how these differences are driven by climatic gradients in temperature and water availability in forest biomes across the globe. We find three consistent trait differences between locally dominant and rare species across all biomes; dominant species are taller, have softer wood and higher loading on the multivariate stem strategy axis (related to narrow tracheids and thick bark). The difference between traits of dominant and rare species is more strongly driven by temperature compared to water availability, as temperature might affect a larger number of traits. Therefore, climate change driven global temperature rise may have a strong effect on trait differences between dominant and rare tree species and may lead to changes in species abundances and therefore strong community reassembly.

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Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)

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NATURE 2022年第7938期612卷 E7-E7页

作者： Mishra, Aniket Malik, Rainer Hachiya, Tsuyoshi Jurgenson, Tuuli Namba, Shinichi Posner, Daniel C. Kamanu, Frederick K. Koido, Masaru Le Grand, Quentin Shi, Mingyang He, Yunye Georgakis, Marios K. Caro, Ilana Krebs, Kristi Liaw, Yi-Ching Vaura, Felix C. Lin, Kuang Winsvold, Bendik Slagsvold Srinivasasainagendra, Vinodh Parodi, Livia Bae, Hee-Joon Chauhan, Ganesh Chong, Michael R. Tomppo, Liisa Akinyemi, Rufus Roshchupkin, Gennady V. Habib, Naomi Jee, Yon Ho Thomassen, Jesper Qvist Abedi, Vida Carcel-Marquez, Jara Nygaard, Marianne Leonard, Hampton L. Yang, Chaojie Yonova-Doing, Ekaterina Knol, Maria J. Lewis, Adam J. Judy, Renae L. Ago, Tetsuro Amouyel, Philippe Armstrong, Nicole D. Bakker, Mark K. Bartz, Traci M. Bennett, David A. Bis, Joshua C. Bordes, Constance Borte, Sigrid Cain, Anael Ridker, Paul M. Cho, Kelly Chen, Zhengming Cruchaga, Carlos Cole, John W. de Jager, Phil L. de Cid, Rafael Endres, Matthias Ferreira, Leslie E. Geerlings, Mirjam I. Gasca, Natalie C. Gudnason, Vilmundur Hata, Jun He, Jing Heath, Alicia K. Ho, Yuk-Lam Havulinna, Aki S. Hopewell, Jemma C. Hyacinth, I. Hyacinth Inouye, Michael Jacob, Mina A. Jeon, Christina E. Jern, Christina Kamouchi, Masahiro Keene, Keith L. Kitazono, Takanari Kittner, Steven J. Konuma, Takahiro Kumar, Amit Lacaze, Paul Launer, Lenore J. Lee, Keon-Joo Lepik, Kaido Li, Jiang Li, Liming Manichaikul, Ani Markus, Hugh S. Marston, Nicholas A. Meitinger, Thomas Mitchell, Braxton D. Montellano, Felipe A. Morisaki, Takayuki Mosley, Thomas H. Nalls, Mike A. Nordestgaard, Borge G. O'Donnell, Martin J. Okada, Yukinori Onland-Moret, N. Charlotte Ovbiagele, Bruce Peters, Annette Psaty, Bruce M. Rich, Stephen S. Rosand, Jonathan Sabatine, Marc S. Sacco, Ralph L. Saleheen, Danish Sandset, Else Charlotte Salomaa, Veikko Sargurupremraj, Muralidharan Sasaki, Makoto Satizabal, Claudia L. Schmidt, Carsten O. Shimizu, Atsushi Smith, Nicholas L. Sloane, Kelly L. Sutoh, Yoichi Sun, Yan V. Tanno, Kozo Tiedt, Steffen Tatlisumak, Turgut Torres-Aguila, Nuria P. Tiwari, Hemant K. Tregouet, Bordeaux Population Health Research Center University of Bordeaux Inserm UMR 1219 Bordeaux France Department of Public Health Bordeaux University Hospital Bordeaux France Department of Neurology Memory Clinic Bordeaux University Hospital Bordeaux France Department of Neurology Institute for Neurodegenerative Diseases CHU de Bordeaux Bordeaux France Institute for Stroke and Dementia Research (ISD) University Hospital LMU Munich Munich Germany Center for Genomic Medicine Massachusetts General Hospital Boston MA USA Program in Medical and Population Genetics Broad Institute of Harvard and the Massachusetts Institute of Technology Cambridge MA USA Munich Cluster for Systems Neurology Munich Germany German Center for Neurodegenerative Diseases (DZNE) Munich Germany Iwate Tohoku Medical Megabank Organization Iwate Medical University Iwate Japan Estonian Genome Centre Institute of Genomics University of Tartu Tartu Estonia Institute of Mathematics and Statistics University of Tartu Tartu Estonia Department of Computational Biology University of Lausanne Lausanne Switzerland Swiss Institute of Bioinformatics Lausanne Switzerland University Center for Primary Care and Public Health Lausanne Switzerland Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan Department of Genome Informatics Graduate School of Medicine The University of Tokyo Tokyo Japan Laboratory for Systems Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan Laboratory of Statistical Immunology Immunology Frontier Research Center (WPI-IFReC) Osaka University Suita Japan Integrated Frontier Research for Medical Science Division Institute for Open and Transdisciplinary Research Initiatives Osaka University Suita Japan Center for Infectious Disease Education and Research (CiDER) Osaka University Suita Japan Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) VA Boston Healthcare System Boston MA USA TIMI S

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Mapping the Human Body at Cellular Resolution -- The NIH Common Fund Human BioMolecular Atlas program

arXiv

引用

arXiv 2019年

作者： Snyder, Michael P. Lin, Shin Posgai, Amanda Atkinson, Mark Regev, Aviv Rood, Jennifer Rozenblatt-Rosen, Orit Gaffney, Leslie Hupalowska, Anna Satija, Rahul Gehlenborg, Nils Shendure, Jay Laskin, Julia Harbury, Pehr Nystrom, Nicholas A. Bar-Joseph, Ziv Zhang, Kun Börner, Katy Lin, Yiing Conroy, Richard Procaccini, Dena Roy, Ananda L. Pillai, Ajay Brown, Marishka Galis, Zorina S. Cai, Long Shendure, Jay Trapnell, Cole Lin, Shin Jackson, Dana Snyder, Michael P. Nolan, Garry Greenleaf, William James Lin, Yiing Plevritis, Sylvia Ahadi, Sara Lee, Hayan Nevins, Stephanie Esplin, Ed Horning, Aaron Bahmani, Amir Zhang, Kun Sun, Xin Jain, Sanjay Hagood, James Kharchenko, Peter Atkinson, Mark Bodenmiller, Bernd Brusko, Todd Clare-Salzler, Michael Nick, Harry Otto, Kevin Posgai, Amanda Wasserfall, Clive Maffioletti, Sergio Caprioli, Richard M. Spraggins, Jeffrey M. Gutierrez, Danielle Patterson, Nathan Heath Neumann, Elizabeth K. Harris, Raymond deCaestecker, Mark de Plas, Raf Van Lau, Ken Cai, Long Yuan, Guo-Cheng Zhu, Qian Dries, Ruben Yin, Peng Saka, Sinem K. Kishi, Jocelyn Y. Wang, Yu Goldaracena, Isabel Laskin, Julia Ye, DongHye Burnum-Johnson, Kristin E. Piehowski, Paul D. Ansong, Charles Zhu, Ying Harbury, Pehr Desai, Tushar Mulye, Jay Chou, Peter Nagendran, Monica Bar-Joseph, Ziv Teichmann, Sarah A. Paten, Benedict Murphy, Robert F. Ma, Jian Kiselev, Vladimir Yu Kingsford, Carl Ricarte, Allyson Ruffalo, Matthew Gehlenborg, Nils Kharchenko, Peter Vella, Margaret McCallum, Chuck Börner, Katy Cross, Leonard E. Friedman, Samuel H. Heiland, Randy Herr, Bruce Macklin, Paul Quardokus, Ellen M. Record, Lisel Sluka, James P. Weber, Griffin M. Nystrom, Nicholas A. Silverstein, Jonathan C. Blood, Philip D. Ropelewski, Alexander J. Shirey, William E. Mabee, Paula Lenhardt, W. Christopher Robasky, Kimberly Michailidis, Stavros Satija, Rahul Marioni, John Regev, Aviv Butler, Andrew Stuart, Tim Fisher, Eyal Ghazanfar, Shila Rood, Jennifer Gaffney, Leslie Ersalan, Gokcen Biancalani, Tommaso Conroy, Richard Procaccini, Dena Roy, Anan School of Medicine Stanford University 300 Pasteur Drive United States Department of Genetics Stanford School of Medicine StanfordCA94305 United States Department of Medicine University of Washington SeattleWA98195 United States Department of Pathology University of Florida Diabetes Institute GainesvilleFL32610 United States Klarman Cell Observatory Broad Institute of MIT and Harvard CambridgeMA02142 United States Howard Hughes Medical Institute Koch Institute of Integrative Cancer Research Department of Biology Massachusetts Institute of Technology CambridgeMA02140 United States New York Genome Center New York CityNY10013 United States New York University New YorkNY10012 United States Department of Biomedical Informatics Harvard Medical School BostonMA02115 United States Department of Genome Sciences University of Washington SeattleWA98105 United States Department of Chemistry Purdue University West LafayetteIN47907 United States Department of Biochemistry Stanford University School of Medicine StanfordCA94305 United States Pittsburgh Supercomputing Center Carnegie Mellon University PittsburghPA15213 United States Department of Computational Biology School of Computer Science Carnegie Mellon University PittsburghPA15213 United States Department of Bioengineering University of California San Diego La JollaCA92093 United States Department of Intelligent Systems Engineering School of Informatics Computing and Engineering Indiana University BloomingtonIN47408 United States Department of Surgery Washington University School of Medicine St LouisMO63110 United States Division of Program Coordination Planning and Strategic Initiatives National Institutes of Health BethesdaMD20892 United States National Human Genome Research Institute National Institutes of Health BethesdaMD20892 United States National Heart Lung and Blood Institute National Institutes of Health BethesdaMD20892 United States Caltech-UW TMC Departmen

Transformative technologies are enabling the construction of three dimensional (3D) maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible 3D molecular and cellular atlas of the human body, in health and various disease settings. Copyright © 2019, The Authors. All rights reserved.

关键词： Mapping

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