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Systems Biology Volume II: Networks, Models, and Applications Series in Systems Biology Edited by Dennis Shasha, New York University EDITORIAL BOARD Michael Ashburner, University of Cambridge Amos Bairoch, Swiss Institute of Bioinformatics Charles Cantor, Sequenom, Inc. Leroy Hood, Institute for Systems Biology Minoru Kanehisa, Kyoto University Raju Kucherlapati, Harvard Medical School Systems Biology describes the discipline that seeks to understand biological phenomena on a large scale: the association of gene with function, the detailed modeling of the interaction among proteins and metabolites, and the function of cells. Systems Biology has wide-ranging application, as it is informed by several underlying disciplines, including biology, computer science, mathematics, physics, chemistry, and the social sciences. The goal of the series is to help practitioners and researchers understand the ideas and technologies underlying Systems Biology. The series volumes will combine biological insight with principles and methods of computational data analysis. Cellular Computing, edited by Martyn Amos Systems Biology, Volume I: Genomics, edited by Isidore Rigoutsos and Gregory Stephanopoulos Systems Biology, Volume II: Networks, Models, and Applications, edited by Isidore Rigoutsos and Gregory Stephanopoulos Systems Biology Volume II: Networks, Models, and Applications Edited by Isidore Rigoutsos & Gregory Stephanopoulos 1 2007 1 Oxford University Press, Inc., publishes works that further Oxford University’s objective of excellence in research, scholarship, and education. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Copyright © 2007 by Oxford University Press, Inc. Published by Oxford University Press, Inc. 198 Madison Avenue, New York, New York 10016 www.oup.com Oxford is a registered trademark of Oxford University Press. All rights reserved. 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, or otherwise, without the prior permission of Oxford University Press. Library of Congress Cataloging-in-Publication Data Systems biology/edited by Isidore Rigoutsos and Gregory Stephanopoulos. v. ; cm.—(Series in systems biology) Includes bibliographical references and indexes. Contents: 1. Genomics—2. Networks, models, and applications. ISBN-13: 978-0-19-530081-9 (v. 1) ISBN 0-19-530081-5 (v. 1) ISBN-13: 978-0-19-530080-2 (v. 2) ISBN 0-19-530080-7 (v. 2) 1. Computational biology. 2. Genomics. 3. Bioinformatics. I. Rigoutsos, Isidore. II. Stephanopoulos, G. III. Series. [DNLM: 1. Genomics. 2. Computational Biology. 3. Models, Genetic. 4. Systems Biology. QU58.5 S995 2006] QH324.2.S97 2006 570—dc22 2005031826 9 8 7 6 5 4 3 2 1 Printed in the United States of America on acid-free paper To our mothers This page intentionally left blank Acknowledgments First and foremost, we wish to thank all the authors who contributed the chapters of these two books. In addition to the professionalism with which they handled all aspects of production, they also applied the highest standards in authoring pieces of work of the highest quality. For their willingness to share their unique expertise on the many facets of systems biology and the energy they devoted to the preparation of their chapters, we are profoundly grateful. Next, we wish to thank Dennis Shasha, the series editor, and Peter Prescott, Senior Editor for Life Sciences, Oxford University Press, for embracing