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A Method to Infer Changed Activity of Metabolic Function from Transcript Profiles
ModeScore: A Method to Infer Changed Activity of Metabolic Function from Transcript Profiles Andreas Hoppe and Hermann-Georg Holzhütter Charité University Medicine Berlin, Institute for Biochemistry, Computational Systems Biochemistry Group [email protected] Abstract Genome-wide transcript profiles are often the only available quantitative data for a particular perturbation of a cellular system and their interpretation with respect to the metabolism is a major challenge in systems biology, especially beyond on/off distinction of genes. We present a method that predicts activity changes of metabolic functions by scoring reference flux distributions based on relative transcript profiles, providing a ranked list of most regulated functions. Then, for each metabolic function, the involved genes are ranked upon how much they represent a specific regulation pattern. Compared with the naïve pathway-based approach, the reference modes can be chosen freely, and they represent full metabolic functions, thus, directly provide testable hypotheses for the metabolic study. In conclusion, the novel method provides promising functions for subsequent experimental elucidation together with outstanding associated genes, solely based on transcript profiles. 1998 ACM Subject Classification J.3 Life and Medical Sciences Keywords and phrases Metabolic network, expression profile, metabolic function Digital Object Identifier 10.4230/OASIcs.GCB.2012.1 1 Background The comprehensive study of the cell’s metabolism would include measuring metabolite concentrations, reaction fluxes, and enzyme activities on a large scale. Measuring fluxes is the most difficult part in this, for a recent assessment of techniques, see [31]. Although mass spectrometry allows to assess metabolite concentrations in a more comprehensive way, the larger the set of potential metabolites, the more difficult [8]. -
The Kyoto Encyclopedia of Genes and Genomes (KEGG)
Kyoto Encyclopedia of Genes and Genome Minoru Kanehisa Institute for Chemical Research, Kyoto University HFSPO Workshop, Strasbourg, November 18, 2016 The KEGG Databases Category Database Content PATHWAY KEGG pathway maps Systems information BRITE BRITE functional hierarchies MODULE KEGG modules KO (KEGG ORTHOLOGY) KO groups for functional orthologs Genomic information GENOME KEGG organisms, viruses and addendum GENES / SSDB Genes and proteins / sequence similarity COMPOUND Chemical compounds GLYCAN Glycans Chemical information REACTION / RCLASS Reactions / reaction classes ENZYME Enzyme nomenclature DISEASE Human diseases DRUG / DGROUP Drugs / drug groups Health information ENVIRON Health-related substances (KEGG MEDICUS) JAPIC Japanese drug labels DailyMed FDA drug labels 12 manually curated original DBs 3 DBs taken from outside sources and given original annotations (GENOME, GENES, ENZYME) 1 computationally generated DB (SSDB) 2 outside DBs (JAPIC, DailyMed) KEGG is widely used for functional interpretation and practical application of genome sequences and other high-throughput data KO PATHWAY GENOME BRITE DISEASE GENES MODULE DRUG Genome Molecular High-level Practical Metagenome functions functions applications Transcriptome etc. Metabolome Glycome etc. COMPOUND GLYCAN REACTION Funding Annual budget Period Funding source (USD) 1995-2010 Supported by 10+ grants from Ministry of Education, >2 M Japan Society for Promotion of Science (JSPS) and Japan Science and Technology Agency (JST) 2011-2013 Supported by National Bioscience Database Center 0.8 M (NBDC) of JST 2014-2016 Supported by NBDC 0.5 M 2017- ? 1995 KEGG website made freely available 1997 KEGG FTP site made freely available 2011 Plea to support KEGG KEGG FTP academic subscription introduced 1998 First commercial licensing Contingency Plan 1999 Pathway Solutions Inc. -
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]. -
Gene Prediction: the End of the Beginning Comment Colin Semple
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central http://genomebiology.com/2000/1/2/reports/4012.1 Meeting report Gene prediction: the end of the beginning comment Colin Semple Address: Department of Medical Sciences, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. E-mail: [email protected] Published: 28 July 2000 reviews Genome Biology 2000, 1(2):reports4012.1–4012.3 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2000/1/2/reports/4012 © GenomeBiology.com (Print ISSN 1465-6906; Online ISSN 1465-6914) Reducing genomes to genes reports A report from the conference entitled Genome Based Gene All ab initio gene prediction programs have to balance sensi- Structure Determination, Hinxton, UK, 1-2 June, 2000, tivity against accuracy. It is often only possible to detect all organised by the European Bioinformatics Institute (EBI). the real exons present in a sequence at the expense of detect- ing many false ones. Alternatively, one may accept only pre- dictions scoring above a more stringent threshold but lose The draft sequence of the human genome will become avail- those real exons that have lower scores. The trick is to try and able later this year. For some time now it has been accepted increase accuracy without any large loss of sensitivity; this deposited research that this will mark a beginning rather than an end. A vast can be done by comparing the prediction with additional, amount of work will remain to be done, from detailing independent evidence. -
Proquest Dissertations
Automated learning of protein involvement in pathogenesis using integrated queries Eithon Cadag A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2009 Program Authorized to Offer Degree: Department of Medical Education and Biomedical Informatics UMI Number: 3394276 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMI Dissertation Publishing UMI 3394276 Copyright 2010 by ProQuest LLC. All rights reserved. This edition of the work is protected against unauthorized copying under Title 17, United States Code. uest ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 University of Washington Graduate School This is to certify that I have examined this copy of a doctoral dissertation by Eithon Cadag and have found that it is complete and satisfactory in all respects, and that any and all revisions required by the final examining committee have been made. Chair of the Supervisory Committee: Reading Committee: (SjLt KJ. £U*t~ Peter Tgffczy-Hornoch In presenting this dissertation in partial fulfillment of the requirements for the doctoral degree at the University of Washington, I agree that the Library shall make its copies freely available for inspection. I further agree that extensive copying of this dissertation is allowable only for scholarly purposes, consistent with "fair use" as prescribed in the U.S. -
Molecular Biology for Computer Scientists
CHAPTER 1 Molecular Biology for Computer Scientists Lawrence Hunter “Computers are to biology what mathematics is to physics.” — Harold Morowitz One of the major challenges for computer scientists who wish to work in the domain of molecular biology is becoming conversant with the daunting intri- cacies of existing biological knowledge and its extensive technical vocabu- lary. Questions about the origin, function, and structure of living systems have been pursued by nearly all cultures throughout history, and the work of the last two generations has been particularly fruitful. The knowledge of liv- ing systems resulting from this research is far too detailed and complex for any one human to comprehend. An entire scientific career can be based in the study of a single biomolecule. Nevertheless, in the following pages, I attempt to provide enough background for a computer scientist to understand much of the biology discussed in this book. This chapter provides the briefest of overviews; I can only begin to convey the depth, variety, complexity and stunning beauty of the universe of living things. Much of what follows is not about molecular biology per se. In order to 2ARTIFICIAL INTELLIGENCE & MOLECULAR BIOLOGY explain what the molecules are doing, it is often necessary to use concepts involving, for example, cells, embryological development, or evolution. Bi- ology is frustratingly holistic. Events at one level can effect and be affected by events at very different levels of scale or time. Digesting a survey of the basic background material is a prerequisite for understanding the significance of the molecular biology that is described elsewhere in the book. -
The EMBL-European Bioinformatics Institute the Hub for Bioinformatics in Europe
The EMBL-European Bioinformatics Institute The hub for bioinformatics in Europe Blaise T.F. Alako, PhD [email protected] www.ebi.ac.uk What is EMBL-EBI? • Part of the European Molecular Biology Laboratory • International, non-profit research institute • Europe’s hub for biological data, services and research The European Molecular Biology Laboratory Heidelberg Hamburg Hinxton, Cambridge Basic research Structural biology Bioinformatics Administration Grenoble Monterotondo, Rome EMBO EMBL staff: 1500 people Structural biology Mouse biology >60 nationalities EMBL member states Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom Associate member state: Australia Who we are ~500 members of staff ~400 work in services & support >53 nationalities ~120 focus on basic research EMBL-EBI’s mission • Provide freely available data and bioinformatics services to all facets of the scientific community in ways that promote scientific progress • Contribute to the advancement of biology through basic investigator-driven research in bioinformatics • Provide advanced bioinformatics training to scientists at all levels, from PhD students to independent investigators • Help disseminate cutting-edge technologies to industry • Coordinate biological data provision throughout Europe Services Data and tools for molecular life science www.ebi.ac.uk/services Browse our services 9 What services do we provide? Labs around the -
Semantic Web
SEMANTIC WEB: REVOLUTIONIZING KNOWLEDGE DISCOVERY IN THE LIFE SCIENCES SEMANTIC WEB: REVOLUTIONIZING KNOWLEDGE DISCOVERY IN THE LIFE SCIENCES Edited by Christopher J. O. Baker1 and Kei-Hoi Cheung2 1Knowledge Discovery Department, Institute for Infocomm Research, Singapore, Singapore; 2Center for Medical Informatics, Yale University School of Medicine, New Haven, CT, USA Kluwer Academic Publishers Boston/Dordrecht/London Contents PART I: Database and Literature Integration Semantic web approach to database integration in the life sciences KEI-HOI CHEUNG, ANDREW K. SMITH, KEVIN Y. L. YIP, CHRISTOPHER J. O. BAKER AND MARK B. GERSTEIN Querying Semantic Web Contents: A case study LOIC ROYER, BENEDIKT LINSE, THOMAS WÄCHTER, TIM FURCH, FRANCOIS BRY, AND MICHAEL SCHROEDER Knowledge Acquisition from the Biomedical Literature LYNETTE HIRSCHMAN, WILLIAM HAYES AND ALFONSO VALENCIA PART II: Ontologies in the Life Sciences Biological Ontologies PATRICK LAMBRIX, HE TAN, VAIDA JAKONIENE, AND LENA STRÖMBÄCK Clinical Ontologies YVES LUSSIER AND OLIVIER BODENREIDER Ontology Engineering For Biological Applications vi Revolutionizing knowledge discovery in the life sciences LARISA N. SOLDATOVA AND ROSS D. KING The Evaluation of Ontologies: Toward Improved Semantic Interoperability LEO OBRST, WERNER CEUSTERS, INDERJEET MANI, STEVE RAY AND BARRY SMITH OWL for the Novice JEFF PAN PART III: Ontology Visualization Techniques for Ontology Visualization XIAOSHU WANG AND JONAS ALMEIDA On Vizualization of OWL Ontologies SERGUEI KRIVOV, FERDINANDO VILLA, RICHARD WILLIAMS, AND XINDONG WU PART IV: Ontologies in Action Applying OWL Reasoning to Genomics: A Case Study KATY WOLSTENCROFT, ROBERT STEVENS AND VOLKER HAARSLEV Can Semantic Web Technologies enable Translational Medicine? VIPUL KASHYAP, TONYA HONGSERMEIER AND SAMUEL J. ARONSON Ontology Design for Biomedical Text Mining RENÉ WITTE, THOMAS KAPPLER, AND CHRISTOPHER J. -
ISMB 2008 Toronto
ISMB 2008 Toronto The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Linial, Michal, Jill P. Mesirov, B. J. Morrison McKay, and Burkhard Rost. 2008. ISMB 2008 Toronto. PLoS Computational Biology 4(6): e1000094. Published Version doi:10.1371/journal.pcbi.1000094 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:11213310 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Message from ISCB ISMB 2008 Toronto Michal Linial1,2, Jill P. Mesirov1,3, BJ Morrison McKay1*, Burkhard Rost1,4 1 International Society for Computational Biology (ISCB), University of California San Diego, La Jolla, California, United States of America, 2 Sudarsky Center, The Hebrew University of Jerusalem, Jerusalem, Israel, 3 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 4 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States of America the integration of students, and for the of ISMB. One meeting in South Asia support of young leaders in the field. (InCoB; http://incob.binfo.org.tw/) has ISMB has also become a forum for already been sponsored by ISCB, and reviewing the state of the art in the many another one in North Asia is going to fields of this growing discipline, for follow. ISMB itself has also been held in introducing new directions, and for an- Australia (2003) and Brazil (2006). -
Methodology for Predicting Semantic Annotations of Protein Sequences by Feature Extraction Derived of Statistical Contact Potentials and Continuous Wavelet Transform
Universidad Nacional de Colombia Sede Manizales Master’s Thesis Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform Author: Supervisor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez A thesis submitted in fulfillment of the requirements for the degree of Master’s on Engineering - Industrial Automation in the Department of Electronic, Electric Engineering and Computation Signal Processing and Recognition Group June 2014 Universidad Nacional de Colombia Sede Manizales Tesis de Maestr´ıa Metodolog´ıapara predecir la anotaci´on sem´antica de prote´ınaspor medio de extracci´on de caracter´ısticas derivadas de potenciales de contacto y transformada wavelet continua Autor: Tutor: Gustavo Alonso Arango Dr. Cesar German Argoty Castellanos Dominguez Tesis presentada en cumplimiento a los requerimientos necesarios para obtener el grado de Maestr´ıaen Ingenier´ıaen Automatizaci´onIndustrial en el Departamento de Ingenier´ıaEl´ectrica,Electr´onicay Computaci´on Grupo de Procesamiento Digital de Senales Enero 2014 UNIVERSIDAD NACIONAL DE COLOMBIA Abstract Faculty of Engineering and Architecture Department of Electronic, Electric Engineering and Computation Master’s on Engineering - Industrial Automation Methodology for predicting semantic annotations of protein sequences by feature extraction derived of statistical contact potentials and continuous wavelet transform by Gustavo Alonso Arango Argoty In this thesis, a method to predict semantic annotations of the proteins from its primary structure is proposed. The main contribution of this thesis lies in the implementation of a novel protein feature representation, which makes use of the pairwise statistical contact potentials describing the protein interactions and geometry at the atomic level. -
Ontology-Based Methods for Analyzing Life Science Data
Habilitation a` Diriger des Recherches pr´esent´ee par Olivier Dameron Ontology-based methods for analyzing life science data Soutenue publiquement le 11 janvier 2016 devant le jury compos´ede Anita Burgun Professeur, Universit´eRen´eDescartes Paris Examinatrice Marie-Dominique Devignes Charg´eede recherches CNRS, LORIA Nancy Examinatrice Michel Dumontier Associate professor, Stanford University USA Rapporteur Christine Froidevaux Professeur, Universit´eParis Sud Rapporteure Fabien Gandon Directeur de recherches, Inria Sophia-Antipolis Rapporteur Anne Siegel Directrice de recherches CNRS, IRISA Rennes Examinatrice Alexandre Termier Professeur, Universit´ede Rennes 1 Examinateur 2 Contents 1 Introduction 9 1.1 Context ......................................... 10 1.2 Challenges . 11 1.3 Summary of the contributions . 14 1.4 Organization of the manuscript . 18 2 Reasoning based on hierarchies 21 2.1 Principle......................................... 21 2.1.1 RDF for describing data . 21 2.1.2 RDFS for describing types . 24 2.1.3 RDFS entailments . 26 2.1.4 Typical uses of RDFS entailments in life science . 26 2.1.5 Synthesis . 30 2.2 Case study: integrating diseases and pathways . 31 2.2.1 Context . 31 2.2.2 Objective . 32 2.2.3 Linking pathways and diseases using GO, KO and SNOMED-CT . 32 2.2.4 Querying associated diseases and pathways . 33 2.3 Methodology: Web services composition . 39 2.3.1 Context . 39 2.3.2 Objective . 40 2.3.3 Semantic compatibility of services parameters . 40 2.3.4 Algorithm for pairing services parameters . 40 2.4 Application: ontology-based query expansion with GO2PUB . 43 2.4.1 Context . 43 2.4.2 Objective . -
Curriculum Vitae – Prof. Anders Krogh Personal Information
Curriculum Vitae – Prof. Anders Krogh Personal Information Date of Birth: May 2nd, 1959 Private Address: Borgmester Jensens Alle 22, st th, 2100 København Ø, Denmark Contact information: Dept. of Biology, Univ. of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. +45 3532 1329, [email protected] Web: https://scholar.google.com/citations?user=-vGMjmwAAAAJ Education Sept 1991 Ph.D. (Physics), Niels Bohr Institute, Univ. of Copenhagen, Denmark June 1987 Cand. Scient. [M. Sc.] (Physics and mathematics), NBI, Univ. of Copenhagen Professional / Work Experience (since 2000) 2018 – Professor of Bionformatics, Dept of Computer Science (50%) and Dept of Biology (50%), Univ. of Copenhagen 2002 – 2018 Professor of Bionformatics, Dept of Biology, Univ. of Copenhagen 2009 – 2018 Head of Section for Computational and RNA Biology, Dept. of Biology, Univ. of Copenhagen 2000–2002 Associate Prof., Technical Univ. of Denmark (DTU), Copenhagen Prices and Awards 2017 – Fellow of the International Society for Computational Biology https://www.iscb.org/iscb- fellows-program 2008 – Fellow, Royal Danish Academy of Sciences and Letters Public Activities & Appointments (since 2009) 2014 – Board member, Elixir, European Infrastructure for Life Science. 2014 – Steering committee member, Danish Elixir Node. 2012 – 2016 Board member, Bioinformatics Infrastructure for Life Sciences (BILS), Swedish Research Council 2011 – 2016 Director, Centre for Computational and Applied Transcriptomics (COAT) 2009 – Associate editor, BMC Bioinformatics Publications § Google Scholar: https://scholar.google.com/citations?user=-vGMjmwAAAAJ § ORCID: 0000-0002-5147-6282. ResearcherID: M-1541-2014 § Co-author of 130 peer-reviewed papers and 2 monographs § 63,000 citations and h-index of 74 (Google Scholar, June 2019) § H-index of 54 in Web of science (June 2019) § Publications in high-impact journals: Nature (5), Science (1), Cell (1), Nature Genetics (2), Nature Biotechnology (2), Nature Communications (4), Cell (1, to appear), Genome Res.