Genomics and Proteomics

[...]... Visualization in Genomics and Proteomics Edited by Francisco Azuaje and Joaquin Dopazo # 2005 John Wiley & Sons, Ltd., ISBN 0-4 7 0-0 943 9-7 4 INTEGRATIVE DATA ANALYSIS AND VISUALIZATION to improve the understanding of how to integrate biological information, which is complex, heterogeneous and geographically distributed The analysis (including discovery) and visualization of relevant biological data patterns... biology in recent decades has been accompanied by growth in the number and size of databases interpreting and describing the results of such experiments In particular, the development of Data Analysis and Visualization in Genomics and Proteomics Edited by Francisco Azuaje and Joaquin Dopazo # 2005 John Wiley & Sons, Ltd., ISBN 0-4 7 0-0 943 9-7 12 BIOLOGICAL DATABASES automated technologies capable of determining... Edited by Francisco Azuaje and Joaquin Dopazo # 2005 John Wiley & Sons, Ltd., ISBN 0-4 7 0-0 943 9-7 1 Integrative Data Analysis and Visualization: Introduction to Critical Problems, Goals and Challenges Francisco Azuaje and Joaquin Dopazo Abstract This chapter introduces fundamental concepts and problems approached in this book A rationale for the application of integrative data analysis and visualization approaches... own database, accessible through a interactive image of the gel itself (Celis and Østergaard, 2004) Interaction databases Interaction databases model a variety of interactions between proteins, RNA, DNA and many other compounds, storing information on how molecules and systems interrelate IntAct is an open source protein interaction database and analysis system It holds interaction data, maintains... every database, useful database links, including and extending those detailed in this section, can be found in Genomics and Proteomics Genomics and Proteomics Bởi: OpenStaxCollege Proteins are the final products of genes, which help perform the function encoded by the gene Proteins are composed of amino acids and play important roles in the cell All enzymes (except ribozymes) are proteins that act as catalysts to affect the rate of reactions Proteins are also regulatory molecules, and some are hormones Transport proteins, such as hemoglobin, help transport oxygen to various organs Antibodies that defend against foreign particles are also proteins In the diseased state, protein function can be impaired because of changes at the genetic level or because of direct impact on a specific protein A proteome is the entire set of proteins produced by a cell type Proteomes can be studied using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins The study of the function of proteomes is called proteomics Proteomics complements genomics and is useful when scientists want to test their hypotheses that were based on genes Even though all cells of a multicellular organism have the same set of genes, the set of proteins produced in different tissues is different and dependent on gene expression Thus, the genome is constant, but the proteome varies and is dynamic within an organism In addition, RNAs can be alternately spliced (cut and pasted to create novel combinations and novel proteins) and many proteins are modified after translation by processes such as proteolytic cleavage, phosphorylation, glycosylation, and ubiquitination There are also protein-protein interactions, which complicate the study of proteomes Although the genome provides a blueprint, the final architecture depends on several factors that can change the progression of events that generate the proteome Metabolomics is related to genomics and proteomics Metabolomics involves the study of small molecule metabolites found in an organism The metabolome is the complete set of metabolites that are related to the genetic makeup of an organism Metabolomics offers an opportunity to compare genetic makeup and physical characteristics, as well as genetic makeup and environmental factors The goal of metabolome research is to identify, quantify, and catalogue all of the metabolites that are found in the tissues and fluids of living organisms 1/5 Genomics and Proteomics Basic Techniques in Protein Analysis The ultimate goal of proteomics is to identify or compare the proteins expressed from a given genome under specific conditions, study the interactions between the proteins, and use the information to predict cell behavior or develop drug targets Just as the genome is analyzed using the basic technique of DNA sequencing, proteomics requires techniques for protein analysis The basic technique for protein analysis, analogous to DNA sequencing, is mass spectrometry Mass spectrometry is used to identify and determine the characteristics of a molecule Advances in spectrometry have allowed researchers to analyze very small samples of protein X-ray crystallography, for example, enables scientists to determine the three-dimensional structure of a protein crystal at atomic resolution Another protein imaging technique, nuclear magnetic resonance (NMR), uses the magnetic properties of atoms to determine the threedimensional structure of proteins in aqueous solution Protein microarrays have also been used to study interactions between proteins Large-scale adaptations of the basic two-hybrid screen ([link]) have provided the basis for protein microarrays Computer software is used to analyze the vast amount of data generated for proteomic analysis Genomic- and proteomic-scale analyses are part of systems biology Systems biology is the study of whole biological systems (genomes and proteomes) based on interactions within the system The European Bioinformatics Institute and the Human Proteome Organization (HUPO) are developing and establishing effective tools to sort through the enormous pile of systems biology data Because proteins are the direct products of genes and reflect activity at the genomic level, it is natural to use proteomes to compare the protein profiles of different cells to identify proteins and genes involved in disease processes Most pharmaceutical drug trials target proteins Information obtained from proteomics is being used to identify novel drugs and understand their mechanisms of action 2/5 Genomics and Proteomics Two-hybrid screening is used to determine whether two proteins interact In this method, a transcription factor is split into a DNA-binding domain (BD) and an activator domain (AD) The binding domain is able to bind the promoter in the absence of the activator domain, but it does not turn on transcription A protein called the bait is attached to the BD, and a protein called the prey is attached to the AD Transcription occurs only ... guoxingzhong and huangzhiman www.dnathink.org 2003.3.5 GENOMICS AND PROTEOMICS Functional and Computational Aspects GENOMICS AND PROTEOMICS Functional and Computational Aspects Edited by Sándor Suhai Deutsches Krebsforschungszentrum Heidelberg, Germany KLUWER ACADEMIC PUBLISHERS New York, Boston, Dordrecht, London, Moscow eBook ISBN: Print ISBN: ©2002 Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow All rights reserved No part of this eBook may be reproduced or transmitted in any form or by any means, electronic, mechanical, recording, or otherwise, without written consent from the Publisher Created in the United States of America Visit Kluwer Online at: http://www.kluweronline.com and Kluwer's eBookstore at: http://www.ebooks.kluweronline.com 0-306-46823-9 0-306-46312-1 PREFACE Genome research will certainly be one of the most important and exciting scien - tific disciplines of the 21st century. Deciphering the structure of the human genome, as well as that of several model organisms, is the key to our understanding how genes func - tion in health and disease. With the combined development of innovative tools, resources, scientific know - how, and an overall functional genomic strategy, the origins of human and other organisms’ genetic diseases can be traced. Scientific research groups and devel - opmental departments of several major pharmaceutical and biotechnological companies are using new, innovative strategies to unravel how genes function, elucidating the gene protein product, understanding how genes interact with others - both in health and in the disease state. Presently, the impact of the applications of genome research on our society in medicine, agriculture and nutrition will be comparable only to that of communication technologies. In fact, computational methods, including networking, have been playing a substantial role even in genomics and proteomics from the beginning. We can observe, however, a fundamental change of the paradigm in life sciences these days: research focused until now mostly on the study of single processes related to a few genes or gene products, but due to technical developments of the last years we can now potentially identify and analyze all genes and gene products of an organism and clarify their role in the network of life processes. This breakthrough in life sciences is gaining speed world - wide and its impact on biology is comparable only to that of microchips on information technology. The main purpose of the International Symposium on Genomics and Proteomics: Functional and Computational Aspects, held October 4–7, 1998 at the Deutsches Krebsforschungszentrum (DKFZ) in Heidelberg, was to give an overview of the present state of the unique relationship between bioinformatics and experimental genome research. The five main sessions, under the headings: expression analysis; functional gene identification; functional aspects of higher order DNA - structure; from protein sequence to structure and function; and genetic and medical aspects of genomics, com - prised both computational work and experimental studies to synergetically unify both approaches. The content of this volume was presented mostly as plenary lectures. The confer - ence was held at the same time as the Annual Meeting of the Gesellschaft fu r Genetik (GfG). It is a great pleasure to thank Professor Harald zur Hausen and the coworkers of DKFZ for their help and hospitality extended to the lecturers and participants during the meeting. We would also like PLANT GENOMICS AND PROTEOMICS PLANT GENOMICS AND PROTEOMICS CHRISTOPHER A. CULLIS A JOHN WILEY & SONS, INC., PUBLICATION Copyright © 2004 by John Wiley & Sons, Inc. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400, fax 978-646-8600, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008. 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Wiley also publishes its books in a variety of electronic formats. Some content that appears in print, however, may not be available in electronic format. Library of Congress Cataloging-in-Publication Data: Cullis, Christopher A., 1945– Plant genomics and proteomics / Christopher A. Cullis. p. cm. Includes bibliographical references and index. ISBN 0-471-37314-1 1. Plant genomes. 2. Plant proteomics. I. Title. QK981.C85 2004 572.8¢62—dc21 2003013088 Printed in the United States of America. 10987654321 CONTENTS ACKNOWLEDGMENTS , VII INTRODUCTION , IX 1THE STRUCTURE OF PLANT GENOMES, 1 2T HE BASIC TOOLBOX—ACQUIRING FUNCTIONAL GENOMIC DATA, 23 3S EQUENCING STRATEGIES, 47 4G ENE DISCOVERY, 69 5C ONTROL OF GENE EXPRESSION, 89 6F UNCTIONAL GENOMICS, 107 7I NTERACTIONS WITH THE EXTERNAL ENVIRONMENT, 131 8I DENTIFICATION AND MANIPULATION OF COMPLEX TRAITS, 147 9B IOINFORMATICS, 167 10 B IOETHICAL CONCERNS AND THE FUTURE OF PLANT GENOMICS, 189 A FTERWORD, 201 I NDEX, 203 V VII ACKNOWLEDGMENTS This book would not have been possible without the contributions of two individuals. First, I would like to thank my wife Margaret, whose efforts in reading the drafts and suggesting clarifications were invaluable. Any obscure or erroneous passages are certainly not her responsibility; she prob- ably just could not get me to change my mind. Second, I would like to thank my son Oliver, with whom I shared the first attempts at writing a book and who contributed with comments on the clarity of early drafts. INTRODUCTION What possible rationale is there for developing a genomics text that is focused on only the plant kingdom? Clearly, there are major differences between plants and animals in many of their fundamental [...]... activities that are a kind of binding and involve binding of tRNA Formation of ternary complex, formation of initiation complex, formation of termination complex, binding to A site, normal reading, misreading, halting, frame shifting Activities inhibited by tobramycin and mupirocin What processes might be affected in a given disorder? Amino acid acylation Inhibiting “normal reading” (no supply of normal... biochemical interactions xi xii PREFACE System-level understanding of biology is derived using mathematical and engineering methods to understand complex biological processes It exposes readers with biology background to the latest developments in proteomics and genomics engineering It also addresses the needs of both students and postdoctoral fellows in computer science and mathematics who are interested in. .. body The integration and application of mathematics, engineering, physics and computer science have been recently used to better understand the complex biological systems by examining the structure and dynamics of cell and organ functions This emerging field called Genomics and Proteomics Engineering has gained tremendous interest among molecular and cellular researchers since it provides a continuous... described in the methods and tools section Our resulting framework possesses the following properties: (1) it allows qualitative modeling of structural and functional aspects of a biological system, (2) it includes biological and medical concept models to allow for querying biomedical information using biomedical abstractions, (3) it allows Genomics and Proteomics Engineering in Medicine and Biology. .. biological and biomedical challenges The main objective of this edited book is to provide information for biological science and biomedical engineering students and researchers in genomics and proteomics sciences and systems biology Although an understanding of genes and proteins are important, the focus is on understanding a system’s structure and dynamics of several gene regulatory networks and their... interested in doing research in biology and bioengineering since the book provides exceptional insights into the fundamental challenges in biology I am grateful to Jeanne Audino of the IEEE Press and Lisa Van Horn of Wiley for their help during the editing of this book Working in concert with them and the contributors really helped me with content development and to manage the peer-review process Finally,... Nianhua Li Background e development of an effective vaccine against all strains of Neisseria meningitidis (meningococcus), the major cause of life-threatening bacterial meningitis and septicemia, is a priority for infectious disease research. Meningococci can be classified into serogroups based on the structure of their extracellular capsular polysac cha- ride, with serogroups B and C being traditionally res- ponsible for the majority of invasive disease in most temperate countries, and serogroup A causing epidemic infections in sub-Saharan Africa. e first generation of vaccines contained purified polysaccharides from serogroups A and C that induced antibodies that promoted complement-mediated serum bactericidal activity (SBA), the correlate of protective immunity, against the respective serogroups. Tetravalent polysaccharide vaccines were later produced by the addition of serogroups Y and W135. However, such vaccines suffer from poor immunogenicity as a conse- quence of the inability of polysaccharide antigens to induce an effective T-helper-cell response. In adults, they produce only a short-lived antibody response and fail to induce immunological memory. Furthermore, they are non-immunogenic in infants, the main potential target group for meningococcal vaccines. Second-generation vaccines were subsequently developed in which the capsular polysaccharides were covalently linked to carrier proteins in order to induce a T-helper-cell response. Such polysaccharide vaccines produce a long-lived IgG response and induce immunological memory even in infants. e first such vaccine, a serogroup C conjugate, was introduced into the UK immunization program in 1999 and has been extremely effective in reducing cases of serogroup C infections [1]. Unfortunately, none of the above strategies have been applicable to infection caused by serogroup B meningo- cocci, which is the major serogroup associated with invasive disease in most western countries. e sero- group B capsular polysaccharide is non-immunogenic even in adults, due to molecular mimicry of neural cell adhesion molecules expressed on developing fetal brain tissue [2]. Alternative strategies have focused on the vaccine potential of subcapsular antigens. Experimental vaccines have been based on outer membrane (OM) ‘blebs’ released from the surface of meningococci during growth and from which toxic lipopolysaccharide has been selectively removed by extraction with deoxycholate detergent. Such outer membrane vesicle (OMV) vaccines have been used in attempts to control outbreaks of serogroup B infection in countries such as Norway, Cuba and New Zealand when epidemics have been caused by one predominant serosubtype [3-5]. e success of such Abstract There is a particular need for an eective vaccine against life-threatening meningitis and septicemia caused by Neisseria meningitidis (meningococcus) serogroup B strains. Vaccine strategies incorporating capsular polysaccharide have proved eective against other meningococcal serogroups, but are not applicable to serogroup B. Attention has therefore focused on the subcapsular outer membrane protein antigens as potential vaccine components. The sequencing of genomes from three serogroups and the availability of the corresponding translated protein databases, combined with the development of sensitive proteomic techniques, have opened up new avenues of meningococcal vaccine research. This has resulted in the identication of potential candidate antigens for incorporation into multicomponent meningococcal vaccines. © 2010 BioMed Central Ltd The influence of genomics and proteomics on the development of potential vaccines against meningococcal infection John E Heckels* † and Jeannette N Williams † R E VIE W *Correspondence: jeh@soton.ac.uk Molecular Microbiology Group, Sir Henry Wellcome Laboratories, Division of Infection, Inammation and Immunity, University of Southampton Faculty of Medicine, ... diseased state 4/5 Genomics and Proteomics D Free Response How has proteomics been used in cancer detection and treatment? Proteomics has provided a way to detect biomarkers and protein signatures,... target proteins Information obtained from proteomics is being used to identify novel drugs and understand their mechanisms of action 2/5 Genomics and Proteomics Two-hybrid screening is used to... are CA-125 for ovarian cancer and PSA for prostate cancer Protein 3/5 Genomics and Proteomics signatures may be more reliable than biomarkers to detect cancer cells Proteomics is also being used