Japan Partnering Awards 2000-2020
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Applied Category Theory for Genomics – an Initiative
Applied Category Theory for Genomics { An Initiative Yanying Wu1,2 1Centre for Neural Circuits and Behaviour, University of Oxford, UK 2Department of Physiology, Anatomy and Genetics, University of Oxford, UK 06 Sept, 2020 Abstract The ultimate secret of all lives on earth is hidden in their genomes { a totality of DNA sequences. We currently know the whole genome sequence of many organisms, while our understanding of the genome architecture on a systematic level remains rudimentary. Applied category theory opens a promising way to integrate the humongous amount of heterogeneous informations in genomics, to advance our knowledge regarding genome organization, and to provide us with a deep and holistic view of our own genomes. In this work we explain why applied category theory carries such a hope, and we move on to show how it could actually do so, albeit in baby steps. The manuscript intends to be readable to both mathematicians and biologists, therefore no prior knowledge is required from either side. arXiv:2009.02822v1 [q-bio.GN] 6 Sep 2020 1 Introduction DNA, the genetic material of all living beings on this planet, holds the secret of life. The complete set of DNA sequences in an organism constitutes its genome { the blueprint and instruction manual of that organism, be it a human or fly [1]. Therefore, genomics, which studies the contents and meaning of genomes, has been standing in the central stage of scientific research since its birth. The twentieth century witnessed three milestones of genomics research [1]. It began with the discovery of Mendel's laws of inheritance [2], sparked a climax in the middle with the reveal of DNA double helix structure [3], and ended with the accomplishment of a first draft of complete human genome sequences [4]. -
Distinctive Regulatory Architectures of Germline-Active and Somatic Genes in C
Downloaded from genome.cshlp.org on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press Research Distinctive regulatory architectures of germline-active and somatic genes in C. elegans Jacques Serizay, Yan Dong, Jürgen Jänes, Michael Chesney, Chiara Cerrato, and Julie Ahringer The Gurdon Institute and Department of Genetics, University of Cambridge, CB2 1QN Cambridge, United Kingdom RNA profiling has provided increasingly detailed knowledge of gene expression patterns, yet the different regulatory ar- chitectures that drive them are not well understood. To address this, we profiled and compared transcriptional and regu- latory element activities across five tissues of Caenorhabditis elegans, covering ∼90% of cells. We find that the majority of promoters and enhancers have tissue-specific accessibility, and we discover regulatory grammars associated with ubiquitous, germline, and somatic tissue–specific gene expression patterns. In addition, we find that germline-active and soma-specific promoters have distinct features. Germline-active promoters have well-positioned +1 and −1 nucleosomes associated with a periodic 10-bp WW signal (W = A/T). Somatic tissue–specific promoters lack positioned nucleosomes and this signal, have wide nucleosome-depleted regions, and are more enriched for core promoter elements, which largely differ between tissues. We observe the 10-bp periodic WW signal at ubiquitous promoters in other animals, suggesting it is an ancient conserved signal. Our results show fundamental differences in regulatory architectures of germline and somatic tissue–specific genes, uncover regulatory rules for generating diverse gene expression patterns, and provide a tissue-specific resource for future studies. [Supplemental material is available for this article.] Cell type–specific transcription regulation underlies production tissues are achieved and whether expression is governed by dis- of the myriad of different cells generated during development. -
Personal and Population Genomics of Human Regulatory Variation
Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Research Personal and population genomics of human regulatory variation Benjamin Vernot, Andrew B. Stergachis, Matthew T. Maurano, Jeff Vierstra, Shane Neph, Robert E. Thurman, John A. Stamatoyannopoulos,1 and Joshua M. Akey1 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA The characteristics and evolutionary forces acting on regulatory variation in humans remains elusive because of the difficulty in defining functionally important noncoding DNA. Here, we combine genome-scale maps of regulatory DNA marked by DNase I hypersensitive sites (DHSs) from 138 cell and tissue types with whole-genome sequences of 53 geo- graphically diverse individuals in order to better delimit the patterns of regulatory variation in humans. We estimate that individuals likely harbor many more functionally important variants in regulatory DNA compared with protein-coding regions, although they are likely to have, on average, smaller effect sizes. Moreover, we demonstrate that there is sig- nificant heterogeneity in the level of functional constraint in regulatory DNA among different cell types. We also find marked variability in functional constraint among transcription factor motifs in regulatory DNA, with sequence motifs for major developmental regulators, such as HOX proteins, exhibiting levels of constraint comparable to protein-coding regions. Finally, we perform a genome-wide scan of recent positive selection and identify hundreds of novel substrates of adaptive regulatory evolution that are enriched for biologically interesting pathways such as melanogenesis and adipo- cytokine signaling. These data and results provide new insights into patterns of regulatory variation in individuals and populations and demonstrate that a large proportion of functionally important variation lies beyond the exome. -
Genomic Approaches for Understanding the Genetics of Complex Disease
Downloaded from genome.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Perspective Genomic approaches for understanding the genetics of complex disease William L. Lowe Jr.1 and Timothy E. Reddy2,3 1Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA; 2Department of Biostatistics and Bioinformatics, Duke University Medical School, Durham, North Carolina 27708, USA; 3Center for Genomic and Computational Biology, Duke University Medical School, Durham, North Carolina 27708, USA There are thousands of known associations between genetic variants and complex human phenotypes, and the rate of novel discoveries is rapidly increasing. Translating those associations into knowledge of disease mechanisms remains a fundamental challenge because the associated variants are overwhelmingly in noncoding regions of the genome where we have few guiding principles to predict their function. Intersecting the compendium of identified genetic associations with maps of regulatory activity across the human genome has revealed that phenotype-associated variants are highly enriched in candidate regula- tory elements. Allele-specific analyses of gene regulation can further prioritize variants that likely have a functional effect on disease mechanisms; and emerging high-throughput assays to quantify the activity of candidate regulatory elements are a promising next step in that direction. Together, these technologies have created the ability to systematically and empirically test hypotheses about the function of noncoding variants and haplotypes at the scale needed for comprehensive and system- atic follow-up of genetic association studies. Major coordinated efforts to quantify regulatory mechanisms across genetically diverse populations in increasingly realistic cell models would be highly beneficial to realize that potential. -
The Economic Impact and Functional Applications of Human Genetics and Genomics
The Economic Impact and Functional Applications of Human Genetics and Genomics Commissioned by the American Society of Human Genetics Produced by TEConomy Partners, LLC. Report Authors: Simon Tripp and Martin Grueber May 2021 TEConomy Partners, LLC (TEConomy) endeavors at all times to produce work of the highest quality, consistent with our contract commitments. However, because of the research and/or experimental nature of this work, the client undertakes the sole responsibility for the consequence of any use or misuse of, or inability to use, any information or result obtained from TEConomy, and TEConomy, its partners, or employees have no legal liability for the accuracy, adequacy, or efficacy thereof. Acknowledgements ASHG and the project authors wish to thank the following organizations for their generous support of this study. Invitae Corporation, San Francisco, CA Regeneron Pharmaceuticals, Inc., Tarrytown, NY The project authors express their sincere appreciation to the following indi- viduals who provided their advice and input to this project. ASHG Government and Public Advocacy Committee Lynn B. Jorde, PhD ASHG Government and Public Advocacy Committee (GPAC) Chair, President (2011) Professor and Chair of Human Genetics George and Dolores Eccles Institute of Human Genetics University of Utah School of Medicine Katrina Goddard, PhD ASHG GPAC Incoming Chair, Board of Directors (2018-2020) Distinguished Investigator, Associate Director, Science Programs Kaiser Permanente Northwest Melinda Aldrich, PhD, MPH Associate Professor, Department of Medicine, Division of Genetic Medicine Vanderbilt University Medical Center Wendy Chung, MD, PhD Professor of Pediatrics in Medicine and Director, Clinical Cancer Genetics Columbia University Mira Irons, MD Chief Health and Science Officer American Medical Association Peng Jin, PhD Professor and Chair, Department of Human Genetics Emory University Allison McCague, PhD Science Policy Analyst, Policy and Program Analysis Branch National Human Genome Research Institute Rebecca Meyer-Schuman, MS Human Genetics Ph.D. -
Scientific Report for the Year 2000
The Erwin Schr¨odinger International Boltzmanngasse 9 ESI Institute for Mathematical Physics A-1090 Wien, Austria Scientific Report for the Year 2000 Vienna, ESI-Report 2000 March 1, 2001 Supported by Federal Ministry of Education, Science, and Culture, Austria ESI–Report 2000 ERWIN SCHRODINGER¨ INTERNATIONAL INSTITUTE OF MATHEMATICAL PHYSICS, SCIENTIFIC REPORT FOR THE YEAR 2000 ESI, Boltzmanngasse 9, A-1090 Wien, Austria March 1, 2001 Honorary President: Walter Thirring, Tel. +43-1-4277-51516. President: Jakob Yngvason: +43-1-4277-51506. [email protected] Director: Peter W. Michor: +43-1-3172047-16. [email protected] Director: Klaus Schmidt: +43-1-3172047-14. [email protected] Administration: Ulrike Fischer, Eva Kissler, Ursula Sagmeister: +43-1-3172047-12, [email protected] Computer group: Andreas Cap, Gerald Teschl, Hermann Schichl. International Scientific Advisory board: Jean-Pierre Bourguignon (IHES), Giovanni Gallavotti (Roma), Krzysztof Gawedzki (IHES), Vaughan F.R. Jones (Berkeley), Viktor Kac (MIT), Elliott Lieb (Princeton), Harald Grosse (Vienna), Harald Niederreiter (Vienna), ESI preprints are available via ‘anonymous ftp’ or ‘gopher’: FTP.ESI.AC.AT and via the URL: http://www.esi.ac.at. Table of contents General remarks . 2 Winter School in Geometry and Physics . 2 Wolfgang Pauli und die Physik des 20. Jahrhunderts . 3 Summer Session Seminar Sophus Lie . 3 PROGRAMS IN 2000 . 4 Duality, String Theory, and M-theory . 4 Confinement . 5 Representation theory . 7 Algebraic Groups, Invariant Theory, and Applications . 7 Quantum Measurement and Information . 9 CONTINUATION OF PROGRAMS FROM 1999 and earlier . 10 List of Preprints in 2000 . 13 List of seminars and colloquia outside of conferences . -
Quantum Aspects of Life / Editors, Derek Abbott, Paul C.W
Quantum Aspectsof Life P581tp.indd 1 8/18/08 8:42:58 AM This page intentionally left blank foreword by SIR ROGER PENROSE editors Derek Abbott (University of Adelaide, Australia) Paul C. W. Davies (Arizona State University, USAU Arun K. Pati (Institute of Physics, Orissa, India) Imperial College Press ICP P581tp.indd 2 8/18/08 8:42:58 AM Published by Imperial College Press 57 Shelton Street Covent Garden London WC2H 9HE Distributed by World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore 596224 USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE Library of Congress Cataloging-in-Publication Data Quantum aspects of life / editors, Derek Abbott, Paul C.W. Davies, Arun K. Pati ; foreword by Sir Roger Penrose. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-1-84816-253-2 (hardcover : alk. paper) ISBN-10: 1-84816-253-7 (hardcover : alk. paper) ISBN-13: 978-1-84816-267-9 (pbk. : alk. paper) ISBN-10: 1-84816-267-7 (pbk. : alk. paper) 1. Quantum biochemistry. I. Abbott, Derek, 1960– II. Davies, P. C. W. III. Pati, Arun K. [DNLM: 1. Biogenesis. 2. Quantum Theory. 3. Evolution, Molecular. QH 325 Q15 2008] QP517.Q34.Q36 2008 576.8'3--dc22 2008029345 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Photo credit: Abigail P. Abbott for the photo on cover and title page. Copyright © 2008 by Imperial College Press All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the Publisher. -
Retrospective Evaluation of Whole Exome and Genome Mutation Calls in 746 Cancer Samples
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2020 Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples Matthew H. Bailey Washington University School of Medicine in St. Louis William U. Meyerson Yale University Lewis Jonathan Dursi Ontario Institute for Cancer Research Liang-Bo Wang Washington University School of Medicine in St. Louis Guanlan Dong Washington University School of Medicine in St. Louis See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Bailey, Matthew H.; Meyerson, William U.; Dursi, Lewis Jonathan; Wang, Liang-Bo; Dong, Guanlan; Liang, Wen-Wei; Weerasinghe, Amila; Li, Shantao; Kelso, Sean; MC3 Working Group; PCAWG novel somatic mutation calling methods working group; Saksena, Gordon; Ellrott, Kyle; Wendl, Michael C.; Wheeler, David A.; Getz, Gad; Simpson, Jared T.; Gerstein, Mark B.; Ding, Li; and PCAWG Consortium, ,"Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples." Nature Communications.,. (2020). https://digitalcommons.wustl.edu/open_access_pubs/9548 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Matthew H. Bailey, William U. Meyerson, Lewis Jonathan Dursi, Liang-Bo Wang, Guanlan Dong, Wen-Wei Liang, Amila Weerasinghe, Shantao Li, Sean Kelso, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Gordon Saksena, Kyle Ellrott, Michael C. Wendl, David A. Wheeler, Gad Getz, Jared T. -
On the Origin of Darwinism
Downloaded from genome.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Preface On the origin of Darwinism Charles Darwin was almost scooped. A quintessential thinker, af- and W. Ford Doolittle and Olga Zhaxybayeva take a Darwinist ter five years voyaging around the globe on the HMS Beagle and view in demonstrating there’s no universally applicable pro- filling notebooks upon notebooks with his careful observations, karyotic ‘‘species’’ concept, but argue that, in the absence of spe- he did not rush to widely disseminate the conclusions of his field cies definitions, progress in metagenomics will surely guide us study. Almost 20 years passed during which he further reflected on toward a deeper understanding of evolution in these populations what he called ‘‘his theory’’ before he was urged to publish si- (Doolittle and Zhaxybayeva 2009). These reviews emphasize the multaneously with Alfred Russell Wallace, another naturalist and advances in our understanding of evolutionary concepts made great thinker, who had independently formulated similar con- possible by progress in genomic research, outline the current clusions on variation within species and survival of the fittest challenges we face, and offer likely paths ahead over the next few (Darwin and Wallace 1858). These first extracts from Darwin’s years. memoir were short and merely outlined what Darwin termed Primary research reports in this special issue all reflect Dar- ‘‘natural selection,’’ but they established that he was the father of winian themes. They include detailed analyses of fine-scale pop- what we now know to be one of the greatest conceptual con- ulation structure, human genetic variation, and recent positive tributions to science and society. -
Computational Proteomics for Genome Annotation
A thesis submitted to The University of Manchester for the Degree of PhD in the Faculty of Life Sciences Computational Proteomics for Genome Annotation Paul David Blakeley January 2013 1 List of Contents List of Figures ....................................................................................................................... 5 List of Tables ........................................................................................................................ 6 Abstract ................................................................................................................................. 7 Declaration ............................................................................................................................ 8 Copyright .............................................................................................................................. 9 Acknowledgements ............................................................................................................. 10 The Author .......................................................................................................................... 11 Rationale for an Alternative Format Thesis .................................................................... 12 Abbreviations ..................................................................................................................... 13 Chapter 1: Introduction .................................................................................................... 14 1.1. Genome annotation -
Quantum Biology: Current Status and Opportunities
An international interdisciplinary workshop Quantum Biology: Current Status and Opportunities 17-18 September 2012 University of Surrey, UK Programme Our Sponsors BBSRC The Biotechnology and Biological Sciences Research Council (BBSRC) Is the UK’s principal public founder of basic and strategic research across the biosciences. Part of the BBSRC’s mission Is to promote public awareness and discussion about issues surrounding how bioscience research is conducted in the applications of research outcomes. www.bbsrc.ac.uk The Institute of Advanced Studies The Institute of Advanced Studies at the University of Surrey hosts small-scale, scientific and scholarly meetings of leading academics from all over the world to discuss specialist topics away from the pressure of everyday work. The events are multidisciplinary, bringing together scholars from different disciplines to share alternative perspectives on common problems. www.ias.surrey.ac.uk MILES (Models and Mathematics in Life and Social Sciences), University of Surrey MILES is a programme of events and funding opportunities to stimulate Surrey’s interdisciplinary research. MILES initiates and fosters projects that bring together academics from mathematics, engineering, computing and physical sciences with those from the life sciences, social sciences, arts, humanities and beyond. www.miles.surrey.ac.uk Quantum Biology: Current Status and Opportunities Introduction Sixty years ago, Erwin Schrödinger, one of the founding fathers of quantum mechanics, puzzled over one of deepest mysteries: what makes genes so durable that they can be passed down through hundreds of generations virtually unchanged? To provide an answer, Schrödinger looked towards the science that he helped to build. In his book, “What is Life?” (first published in 1944), he suggested that life was unique in that some of its properties are generated, not by the familiar statistical laws of classical science, but by the strange and counterintuitive rules of quantum mechanics. -
Life on the Edge: the Coming of Age of Quantum Biology Free
FREE LIFE ON THE EDGE: THE COMING OF AGE OF QUANTUM BIOLOGY PDF Jim Al-Khalili,Johnjoe McFadden | 464 pages | 24 Sep 2015 | Transworld Publishers Ltd | 9780552778077 | English | London, United Kingdom [PDF] [EPUB] Life on the Edge: The Coming of Age of Quantum Biology Download T he scent of an orange, a robin on the wing — nothing could be more festive. But if you think such simple delights are born of simple processes, think again. But life, it seems, is different. The theory goes that the eye of a robin contains a chemical that, when it absorbs light of the right energy, can shuffle its electrons around. This shuffling creates a system that exists, thanks to some quantum jiggery-pokery, in two forms at once — each of which leads to a different outcome in the reaction that follows. And it turns out we, too, harness quantum effects. Indeed such phenomena account, among other things, for the ability of our enzymes to speed up chemical reactions that could otherwise take millennia, and might even be behind our olfactory prowess, allowing us Life on the Edge: The Coming of Age of Quantum Biology recognise the waft of limonene molecules as the scent of an orange. Dig into the science and this book offers fascinating insights — not least that the mirror image of a limonene molecule smells not of oranges, but turpentine. But whether the meatier revelations will elicit the resounding gasp that the authors clearly expect is another matter. But tenacity pays off: the later section exploring how life emerged from the primordial soup will have you gazing at the world in awe.