Encyclopedia of Systems Biology Werner Dubitzky • Olaf Wolkenhauer Kwang-Hyun Cho • Hiroki Yokota Editors Encyclopedia of Systems Biology With 830 Figures and 148 Tables Editors Werner Dubitzky Kwang-Hyun Cho Biomedical Sciences Research Institute Department of Bio and Brain Engineering University of Ulster Korea Advanced Institute of Science and Coleraine, UK Technology (KAIST) Daejeon, Republic of Korea Olaf Wolkenhauer Department of Computer Science Hiroki Yokota University of Rostock Department of Biomedical Engineering Rostock, Germany Rensselaer Polytechnic Institute Troy, NY, USA ISBN 978-1-4419-9862-0 ISBN 978-1-4419-9863-7 (eBook) ISBN 978-1-4419-9864-4 (Print and electronic bundle) DOI 10.1007/ 978-1-4419-9863-7 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013931182 # Springer ScienceþBusiness Media LLC 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer ScienceþBusiness Media (www.springer.com) Preface Systems biology refers to the quantitative analysis of the dynamic interactions among multiple components of a biological system and aims to understand the behavior of the system as a whole. Systems biology involves the development and application of system-theoretic concepts for the study of complex biological systems through iteration over mathematical modeling, computational simulation and biological experimentation. Systems biology could be viewed as a new concept and tool to increase our understanding of biological systems, to develop more directed experi- ments, and to allow accurate predictions. Systems biology is among the most rapidly growing fields of scientific research and technology development. Over the past ten to fifteen years, the research activities in this field have been increasing exponentially. This is evidenced by the number of published papers as well as the growing number of conferences, journals, research institutions and centers, and academic events on the topic of systems biology. While research, development and applications in this field are becoming more widespread, one major challenge is the lack of a single reference resource providing up-to-date overviews and definitions of the major concepts and subjects across the various sub- areas of systems biology. The Encyclopedia of Systems Biology is addressing this lack and provides a unified information resource. It has been conceived as a comprehensive reference work covering all aspects of systems biology, including the investigation of living matter through a tight coupling of biological experimen- tation, mathematical modeling and computational analysis and simulation. The main aim of the Encyclopedia is to provide a complete reference of established knowledge in systems biology – a ‘one-stop shop’ for someone seeking information on key concepts in this field. As a result, the Encyclopedia comprises a broad range of topics relevant in the context of systems biology. The audience targeted by the Encyclopedia includes researchers, developers, teachers, students and practitioners who are studying or working in the field of systems biology. Keeping in mind the varying needs of the potential readership, we have structured and presented the content in a way that is accessible to readers from a wide range of backgrounds. In contrast to encyclopedic online resources, which often rely on the general public to author their content, a key consideration in the development of the Encyclopedia of Systems Biology was to have subject matter experts define the concepts and subjects of systems biology. We believe that there is no other treatment of this subject in terms of depth and authority of the field. Ultimately, systems biology represents a trans-disciplinary scientific paradigm, in which researchers from diverse backgrounds work jointly using a shared conceptual framework and combined disciplinary-specific approaches to address complex life science R&D problems. Thus, the Encyclopedia of Systems Biology derives its v vi Preface raison d’eˆtre from a modern trans-disciplinary perspective on how to think about and explore complex biological phenomena. We believe that this new publication will help to define the meaning and scope of systems biology, and to extend the impact that systems biology will have on future developments in the life sciences. Acknowledgments It has taken several years of hard work by many people to bring this Encyclopedia to life. We would like to give our sincere thanks to the members of the Editorial Board, the contributing authors and the reviewers. Without their expertise, dedication and continuous efforts this comprehensive reference work would not exist. We wish to thank Joseph Burns (Senior Editor), Sandra Fabiani (Executive Editor) and Melanie Tucker (Editor) who proposed the project to us and provided invaluable counsel in shaping and developing this reference work. We wish to express our profound gratitude to Sylvia Blago and Simone Giesler from Springer for their outstanding editorial efforts in producing this exciting Encyclopedia. March 2013 Werner Dubitzky, Olaf Wolkenhauer, Kwang-Hyun Cho, Hiroki Yokota Editors-in-Chief Coleraine / Rostock / Daejeon / Indianapolis Editors-in-Chief Werner Dubitzky Biomedical Sciences Research Institute, University of Ulster, Coleraine, UK Olaf Wolkenhauer Department of Computer Science, University of Rostock, Rostock, Germany Kwang-Hyun Cho Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea Hiroki Yokota Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA vii About the Editors Professor Werner Dubitzky currently occupies the Chair of Bioinformatics at the at the University of Ulster, Coleraine, UK. In 1991, he received an MSc in electrical engineering from the University of Applied Sciences, Augsburg, Germany, and in 1997 a Ph.D. in computer science from the University of Ulster at Jordanstown, UK. His main research areas include bioinformatics and computational systems biology, artificial intelligence, data mining and management, multi-scale modelling and simulation, and large-scale computing technology. I was always fascinated by the diversity and complexity in the life sciences. Looking at the intricate inner workings of only a single cell, one wonders if humans will ever fully understand its complicated ways. It is clear to me that a comprehensive understanding of complex life phenomena requires a discipline-crossing approach. To make such an approach efficient, we require a shared trans-disciplinary conceptual framework. I am excited to be involved in the development of the Encyclopedia of Systems Biology, as I see it as an important contribution in the construction of such aframework. ix x About the Editors Professor Olaf Wolkenhauer received first degrees in control engineering from the University of Applied Sciences in Hamburg, Germany and the University of Portsmouth, U.K. in 1994 and his Ph.D. from UMIST in Manchester in 1997). Before moving to the University of Rostock, where he occupies the Chair in Systems Biology & Bioinformatics, he a research lectureship at the Control Systems Centre in Manchester, a joint senior lectureship between the Department of Biomolecular Sciences and the Department of Electrical Engineering and Electronics, at UMIST. Since October 2004 he is an Adjunct Professor in the Department of Electrical Engineering and Computer Science at Case Western Reserve University, Cleveland, USA an became 2005 a fellow of the Stellenbosch Institute for Advanced Study (STIAS). Olaf Wolkenhauer’s research interest is mathematical modelling and data analysis, focussing on nonlinear dynamical systems in molecular and cell biology. Further, detailed information can be obtained from his webpage at www.sbi.uni-rostock.de. Systems