Encyclopedia of Systems Biology

Werner Dubitzky • Olaf Wolkenhauer Kwang-Hyun Cho • Hiroki Yokota Editors

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

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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 experiments, 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 experimentation, 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 biology should not be considered a discipline but an approach to understand complex biological systems. Nonlinear spatio-temporal phenomena, crossing multiple levels of structural and functional organization are the reason why mathematical modelling and simulation can play an important role. The fact that so many different topics come together in systems biology is a challenge but also an additional motivation to advance our understanding of living systems. About the Editors xi

Professor Kwang-Hyun Cho received B.S., M.S., and Ph.D. degrees in electrical engineering from the Korea Advanced Institute of Science and Technology (KAIST) in 1993 (summa cum laude), 1995, and 1998, respectively. He was an Associate Professor at the College of Medicine, Seoul National University, Korea until 2007 and is currently the Chair Professor in the Department of Bio and Brain Engineering at the KAIST and a director of the Laboratory for Systems Biology and Bio-Inspired Engineering (http://sbie.kaist.ac.kr). He was the recipient of the IEEE/IEEK Joint Award for Young IT Engineer, the Young Scientist Award from the President of Korea, and the Walton Fellow Award from Science Foundation of Ireland. He has been working on systems biology with biomedical applications, network evolution, and bio-inspired engineering. His innovative contribution to systems biology and bio-inspired engineering research by combining an engineering approach with biochemical experimentation has led to over 126 high-proﬁle international journal publications. He is currently the Editor-in-Chief of IET Systems Biology (IET, London, U.K.). As a systems scientist, I was intrigued by the complex and puzzling dynamics of living systems. In particular, their self-organizing behaviors and emergent properties led me to think about the fundamental difference of living systems compared to non-living systems from a systems science point of view. Systems biology is the way of approaching answers to such questions and I hope the Encyclopedia of Systems Biology to be a useful travel guide for that expedition. xii About the Editors

Dr Hiroki Yokota is a Professor of Biomedical Engineering at the Purdue School of Engineering and Technology, at Indiana University Purdue University Indianapolis (IUPUI), U.S.A. He is also a Director of Biomechanics and Biomaterials Research Centre at IUPUI. He received a PhD in astronautics from the University of Tokyo (Japan) in 1983, and a PhD in molecular, cellular and developmental biology from Indiana University (U.S.A.) in 1993. He is a fellow of American Institute for Medical and Biological Engineering since 2009. Currently, his main research interests are skeletal biology, molecular and cellular mechanics, and applications of control theories in metabolic processes. Unlike a construction crane’s arm, our long bones are constantly remodeled by a series of destruction events followed by rebuilding. This simpliﬁed comparison through my research of skeletal systems highlights two independent systems design principles in the crane and bone. My sincere hope is that the Encyclopaedia of Systems Biology will assist our understanding of adaptive biological systems and stimulate useful applications of their design principles. Section Editors

Applications in Drug Discovery Nagasuma Chandra Bioinformatics Centre and SERC, Indian Institute of Science, Malleshwaram, Bangalore, India

Artificial Intelligence and Machine Learning Daniel Berrar Tokyo Institute of Technology, Interdisciplinary Graduate School of Science and Engineering, Nagatsuta, Midori-ku, Yokohama, Japan Werner Dubitzky University of Ulster, Coleraine, UK

Aritificial Life Jan T. Kim University of East Anglia, School of Computing Sciences, Norwich, UK

Cancer Carlos Sonnenschein Department of Anatomy and Cellular Biology, Tufts Univer- sity School of Medicine, Boston, MA, USA Ana Soto Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA

Cell Cycle Attila Csika´sz-Nagy CoSBi, The Microsoft Research, Centre for Computational and Systems Biology, University of Trento, Povo (Trento), Italy

Computational MicroRNA Biology Ulf Schmitz Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany Julio Vera Group of Systems Biology for Cancer and Aging, Department of Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany

Gene Regulatory Networks: Modeling, Reconstruction and Analysis Luonan Chen Department of Electrical Engineering and Electronics, Osaka Sangyo University, Daito, Osaka, Japan

xiii xiv Section Editors

Large-Scale and High-Performance Computing Mario Cannataro School of Informatics and Biomedical Engineering, University “Magna Græcia” of Catanzaro, Viale Europa (Localita` Germaneto), Catanzaro, Italy

Mathematical Theory and Methods Daniel A. Beard Department of Physiology, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA Helen Byrne Centre for Mathematical Medicine and Biology, School of Mathemat- ical Sciences, University of Nottingham, Nottingham, UK

Metabolic Networks Osbaldo Resendis-Antonio Systems Biology Group, Instituto Nacional de Medicina Genomica, (INMEGEN), Tlalpan, Mexico City, DF, Mexico

Model Databases Jacky Snoep Department of Biochemistry, University of Stellenbosch, Matieland, South Africa

Philosophical and Foundational Issues Ulrich Krohs Department of Philosophy, University of Hamburg, Hamburg, Germany

Quantitative Experiment Design Ann E. Rundell Biomedical Engineering, Purdue University, West Lafayette, IN, USA

Resources Eduardo Mendoza Department of Computer Science, University of the Philippines, Diliman, Quezon City, Philippines

Single Cell Experiments Feng-Chun Yang Herman B Wells Center for Pediatric Research, Indiana Univer- sity School of Medicine, Indianapolis, IN, USA

Standards, Exchange Formats, Guidelines and Ontologies Chris Taylor EMBL, The European Bioinformatics Institute Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK

Statistical Theory and Methods Eugene Kolker Biomedical and Health Informatics Division, Medical Education and Biomedical Informatics Department, School of Medicine, Seattle, WA, USA Section Editors xv

Structural Network Analysis Nitin Bhardwaj Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA

Systems Approaches to Translational Biomedical Research: Focus on Diagnostic and Prognostic Applications Francisco Azuaje Laboratory of Cardiovascular Research, CRP-Sante, Luxembourg

Systems Immunology Sudipto Saha Centenary Campus, Bose Institute, Kolkata, West Bengal, India

Text Mining Jorg€ Hakenberg Department of Computer Science and Department of Biomedical Informatics, Arizona State University, Tempe, AZ, USA

Toponomics Walter Schubert Molecular Pattern Recognition Research Group, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

Transcriptional Regulation Masami Horikoshi Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan

Translational Control and Systems Biology Katsura Asano Division of Biology, Kansas State University, Manhattan, KS, USA

Contributors

Adele A. Abrahamsen Center for Research in Language, University of California, San Diego, La Jolla, CA, USA

Pragyan Acharya Department of Biochemistry, Indian Institute of Science, Ban- galore, Karnataka, India

Naruhiko Adachi Structure-guided Drug Development Project, JBIC Research Institute, Japan Biological Informatics Consortium, Tokyo, Japan

Christoph Adami Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA

Giuseppe Agapito Department of Experimental Medicine and Clinic, University Magna Graecia of Catanzaro, Catanzaro, Italy

Shipra Agrawal BioCOS Life Sciences Pvt. Limited, Institute of Bioinformatics and Applied Biotechnology, Bangalore, Karnataka, India

Baltazar D. Aguda Mathematical Biosciences Institute, Ohio State University, Columbus, OH, USA

Jesu´s Aguilar-Ruiz School of Engineering, Pablo de Olavide University, Escuela Polite´cnica Superior, Seville, Spain

Mario Albrecht Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrucken,€ Germany

Annette A. Alcasabas BioSyntha Technology, Welwyn Garden City, UK

Roberta Alﬁeri Institute for Biomedical Technologies – CNR (Consiglio Nazionale delle Ricerche), Segrate, Milan, Italy

Valencia Alfonso Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

Syed Toufeeq Ali-Ahmed Department of BioMedical Informatics, Vanderbilt University, Nashville, TN, USA

Frank Allgower€ Institute for Systems Theory and Automatic Control, University of Stuttgart, Stuttgart, Germany

Ronnie Alves Instituto de Informa´tica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

xvii xviii Contributors

Flavio Amara Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita` di Milano, Milan, Italy Francesco Amato Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Sophia Ananiadou National Centre for Text Mining, School of Computer Science, University of Manchester, Manchester, UK Hanne Andersen Department of Physics and Astronomy, Centre for Science Studies, Aarhus University, Aarhus, Denmark James Anderson Department of Engineering Science, University of Oxford, Oxford, UK Hifzur Rahman Ansari Bioinformatics Centre, Institute of Microbial Technology, Chandigarh, Chandigarh, India Erick Antezana Department of Biology, Systems Biology Group, Norwegian University of Science and Technology, Trondheim, Norway Dagoberto Armenta-Medina Departamento de Ingenierıá Celular y Biocata´lisis, Instituto de Biotecnologıá, Universidad Nacional Autońoma de Me´xico, Cuernavaca, Morelos, Me´xico Katsura Asano Molecular, Cellular, and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS, USA Diana Ascencio Laboratorio Nacional de Geno´mica para la Biodiversidad, CINVESTAV-IPN, Irapuato, Guanajuato, Mexico Teresa K. Attwood Faculty of Life Sciences and School of Computer Science, University of Manchester, Manchester, UK Claudio Avignone-Rossa Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK M. Madan Babu MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK Walter de Back Centre for High Performance Computing (ZIH), Technical University Dresden, Dresden, Germany David A. Bader School of Computational Science and Engineering, College of Computing, Georgia Institute of Technology, Atlanta, GA, USA Jurg€ Bahler€ Department of Genetics, Evolution and Environment and UCL Cancer Institute, University College London, London, UK Jose´ Ignacio Agulleiro Baldo´ Supercomputing-Algorithms Group, University of Almerıá, Almerıá, Spain Eva Balsa-Canto Ministerio de Economıá y Competitividad, Bioprocess Engineer- ing Group, IIM-CSIC, Vigo, Spain Julio R. Banga Ministerio de Economıá y Competitividad, Bioprocess Engineering Group, IIM-CSIC, Vigo, Spain Contributors xix

Mary Helen Barcellos-Hoff Department of Radiation Oncology and Cell Biology, New York University School of Medicine, New York, NY, USA Andre´ Bardow Institute of Technical Thermodynamics, RWTH Aachen University, Aachen, Germany Neil Andrew D. Bascos Protein Structure and Immunology Laboratory, National Institute of Molecular Biology and Biotechnology, University of the Philippines, Quezon City, Philippines Riza Theresa Batista-Navarro National Centre for Text Mining, Manchester Interdisciplinary Biocentre, Manchester, UK William A. Baumgartner Jr University of Colorado Denver, Aurora, CO, USA Sean Bechhofer School of Computer Science, University of Manchester, Manchester, UK William Bechtel Department of Philosophy and Center for Chronobiology, Univer- sity of California, San Diego, La Jolla, San Diego, CA, USA Elena Beisswanger Jena University Language and Information Engineering (JULIE) Laboratory, Friedrich-Schiller-University Jena, Jena, Germany Xavier Belle´s Institut de Biologia Evolutiva, CSIC-UPF (Universitat Pompoi Fabra), Barcelona, Spain Bertrand Bellier Immunology-Immunopathology-Immunotherapy, UPMC Univer- sity Paris 06, UMR7211, CNRS, UMR7211, INSERM, U959, Paris, France Daniel Berrar Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan Dany Beste Division of Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK Fabrizio Bezzo CAPE-Laboratory, Dipartimento di Ingegneria Industriale, Univer- sity of Padova, Padova, Italy Upinder S. Bhalla Neurobiology, National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India M. M. Srinivas Bharath Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India P. Jayadeva Bhat School of Bioscience and Engineering, Indian Institute of Technology, Mumbai, India Animesh Bhattacharya Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany Leonardo Bich Department of Logic and Philosophy of Science, IAS-Research Center for Life, Mind, and Society, University of the Basque Country, UPV/EHU, Donostia-San Sebastiań, Spain Jose´ Romań Bilbao-Castro Supercomputing-Algorithms Group, University of Almerıá, Almerıá, Spain xx Contributors

Zhao Bing Department of Biochemistry, University of Western Ontario, London, ON, Canada Emanuele G. Biondi CR1-CNRS-Laboratory of Biochemistry and Integrated Structural Biology, Institut de Recherche Interdisciplinaire - IRI CNRS USR3078, Villeneuve d’Ascq, France Jesus Bisbal Departament de Tecnologies de la Informacio´ i les Comunicacions, Universitat Pompeu Fabra, Barcelona, Spain Hagen Blankenburg Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrucken,€ Germany Rainer Blasczyk Hannover Medical School, Institute for Transfusion Medicine, Hannover, Germany Hendrik Blockeel Department of Computer Science, Katholieke Universiteit Leuven, Heverlee, Belgium Leiden Institute of Advanced Computer Science, Universiteit Leiden, Leiden, The Netherlands Olivier Bodenreider Lister Hill National Center for Biomedical Communications, US National Library of Medicine, Bethesda, MD, USA Davide Bolchini School of Informatics, Indiana University, Indianapolis, IN, USA Daniel R. Boutz Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, USA Vani Brahmachari Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India Ryan R. Brinkman Terry Fox Laboratory, BC Cancer Agency, BC Cancer Research Centre, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Randall D. Britten Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Alistair J. P. Brown Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK Gerhard Buck-Sorlin Institut de Recherche en Horticulture et Semences, UMR 1345 (INRA/Agrocampus-ouest/Universite´ d’Angers) Agrocampus Ouest, Angers, France Scott M. Bugenhagen Computational Bioengineering Group, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA Marc Bullock Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Southampton University Hospital NHS Trust, Southamp- ton, UK Richard M. Burian Department of Philosophy, Virginia Tech, Blacksburg, VA, USA Contributors xxi

Michael E. Bushell Department of Microbial and Cellular Sciences, University of Surrey, Guildford, Surrey, UK Gregery T. Buzzard Department of Mathematics, Purdue University, West Lafayette, IN, USA Laurence Calzone Institut Curie – INSERM U900 – Mines ParisTech, Paris, France Anyela Camargo Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Ceredigion, UK Mario Cannataro Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy Virginio Cantoni Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy Computational Biology, KTH Royal Institute of Technology, Stockholm, Sweden Martin Carrier Department of Philosophy, Bielefeld University, Bielefeld, Germany Eugenio Cesario ICAR-CNR (Istituto di Calcolo e Reti ad Alte Prestazioni), Rende, CS, Italy Guilhem Chalancon MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK Alan Champneys Department of Engineering Mathematics, University of Bristol, Bristol, UK Mark R. Chance Center for Proteomics and Bioinformatics and Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA Nagasuma Chandra Department of Biochemistry, Indian Institute of Science, Bangalore, India Rupanjali Chaudhuri G.N. Ramachandran Knowledge Centre for Genome Infor- matics, Institute of Genomics and Integrative Biology, Delhi, India Vijayalakshmi Chelliah EMBL European Bioinformatics Institute, Hinxton, Cambridgeshire, UK Katherine C. Chen Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA James J. Chen U.S. Food and Drug Administration, National Center for Toxico- logical Research (HFT-20), Jefferson, AR, USA Li-Hsunan Chen Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan Xi Chen Advanced Modeling and Applied Computing Laboratory, Department of Mathematics, University of Hong Kong, Hong Kong, China Wai-Ki Ching Advanced Modeling and Applied Computing Laboratory, Depart- ment of Mathematics, University of Hong Kong, Hong Kong, China xxii Contributors

Miew Keen Choong Centre for Health Informatics, Australian Institute for Health Innovation, University of New South Wales, Sydney, NSW, Australia I-Chun Chou The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA Yunfei Chu Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA Andrea Ciliberto IFOM – The FIRC Institute of Molecular Oncology, Milan, Italy Jean Clairambault Equipe-Projet BANG, INRIA Paris-Rocquencourt BP 105, Le Chesnay, Paris, France Amanda Clare Department of Computer Science, Aberystwyth University, Aberystwyth, UK Tim Clark Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Richard H. Clayton Department of Computer Science, University of Sheffield, Sheffield, UK Gilles Clermont Center for Inflammation and Regenerative Modeling, University of Pittsburgh, Pittsburgh, PA, USA George M. Coghill Institute for Complex System and Mathematical Biology, University of Aberdeen, Aberdeen, UK Kevin Bretonnel Cohen Center for Computational Pharmacology, University of Colorado, Aurora, CO, USA Matteo Comin Department Information Engineering, University of Padova, Padova, Italy David Cook AstraZeneca, Translational Patient Safety and Enabling Science, Macclesfield, Chester, UK Carlo Cosentino Department of Clinical and Experimental Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy Richard G. Coˆte´ European Molecular Biology Laboratory, European Bioinformat- ics Institute (EBI), Hinxton, Cambridge, UK Carl F. Craver Philosophy and Philosophy-Neuroscience-Psychology Program, Philosophy Department, Washington University in Saint Louis, St. Louis, MO, USA Attila Csika´sz-Nagy The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Trento, Italy Lalit Darunte Department of Chemical Engineering, Indian Institute of Techno- logy, Mumbai, India Ranjan K. Dash Department of Physiology, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA Jonathan F. Davies Fondazione Bruno Kessler, Trento, Italy Contributors xxiii

Barbara J. Davis Section of Pathology, Tufts Cummings School of Veterinary Medicine Biomedical Sciences, North Grafton, MA, USA

Thomas S. Deisboeck Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA

David S. DeLuca Cancer Genome Analysis Group, The Broad Institute, Cambridge, MA, USA

Alexander DeLuna Laboratorio Nacional de Geno´mica para la Biodiversidad, CINVESTAV-IPN, Irapuato, Guanajuato, Mexico

Andreas Deutsch Center for Information Services and High Performance Compu- ting (ZIH), Technical University Dresden, Dresden, Germany

Rohan Dhiman Center for Pulmonary and Infectious Disease Control, University of Texas Health Science Center at Tyler, Tyler, TX, USA

Akos Dobay Institute of Evolutionary Biology and Environmental Studies (IEU), University of Zurich, Zurich, Switzerland

Maria Pamela Dobay Department of Physics, Ludwig-Maximilians University, Munich, Germany

Andreas Doncic Department of Biology, Stanford University School of Medicine, Stanford, CA, USA

Brecht M. R. Donckels Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium

Piercarlo Dondi Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy

Francis J. Doyle III Department of Chemical Engineering, Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, USA

Andreas Drager€ Center for Bioinformatics, University of Tuebingen, Tuebingen, Germany

Dirk Drasdo Institute National de Recherche en Informatique et en Automatique, Paris–Rocquencourt, France Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany

Andreas Dress University of Bielefeld, Bielefeld, Germany Key Laboratory for Computational Biology (PICB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science and Max Planck Society (CAS–MPG) Partner Institute, Shanghai, China Science Center at “inﬁnity3 GmbH”, Bielefeld, Germany

Franco du Preez SysMO-DB team, Manchester Centre for Integrative Systems Biology, University of Manchester, Manchester, UK

Werner Dubitzky Biomedical Sciences Research Institute, University of Ulster, Coleraine, UK xxiv Contributors

Włodzisław Duch Department of Informatics, Nicolaus Copernicus University, Torun´, Poland School of Computer Engineering, Nanyang Technological University, Singapore, Singapore

Franco duPreez SysMO-DB team, University of Manchester, Manchester Centre for Integrative Systems Biology, Manchester, UK

Harsh Dweep Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Gaurav Dwivedi The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA

Oliver Ebenhoh€ Institute for Complex Systems and Mathematical Biology, University of Aberdeen, Kings College, Old Aberdeen, Aberdeen, UK

Karen Eilbeck Department of Biomedical Informatics, University of Utah, Salt Lake City, UT, USA Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT, USA

Yasser EL-Manzalawy Center for Computational Intelligence, Learning, and Dis- covery, Computer Science, Iowa State University, Ames, IA, USA

Heiko Enderling Center of Cancer Systems Biology, St. Elizabeth’s Medical Cen- ter - CBR 115D, Tufts University School of Medicine, Boston, MA, USA

David Epstein Mathematics Institute, University of Warwick, Warwick, UK Arantza Etxeberria Department of Logic and Philosophy of Science, IAS- Research Center for Life, Mind, and Society, University of the Basque Country, UPV/EHU, Donostia - San Sebastia´n, Spain

Anthony Faiola School of Informatics, Indiana University, Indianapolis, IN, USA Dana Faratian Centre for Molecular Pathology, Institute of Cancer Research, Surrey, UK

Malcolm Farrow School of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne, UK Adrien Faure´ Graduate School of Science and Engineering, Yamaguchi Univesity, Yamaguchi, Japan

Nnenna A. Finn The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA Darren R. Flower School of Life and Health Sciences, Aston University, Birming- ham, UK

Thomas Fober Philipps-Universit€at Marburg, Marburg, Germany Luı´s L. Fonseca Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA Contributors xxv

Christian V. Forst Department of Clinical Sciences, Southwestern Medical Center, University of Texas, Dallas, TX, USA Erika De Francesco Exeura, Rende (CS), Italy Sherry Freiesleben Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, Rostock, Germany Peter Frick Vanderbilt University, Nashville, TN, USA Tamaki Fujimori Human Metabolome Technologies Inc., Tsuruoka, Yamagata, Japan Johannes Furnkranz€ Technical University of Darmstadt, Darmstadt, Germany Alessandro Gaggia Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy Ester M. Garzoń Department of Computer Architecture and Electronics, Univer- sity of Almerıá, Almerıá, Spain Riccardo Gatti Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy Hao Ge School of Mathematical Sciences and Centre for Computational Systems Biology, Fudan University, Shanghai, China Martin Gerner Faculty of Life Sciences, University of Manchester, Manchester, UK Andrew D. Gewitz Institute for Computational and Mathematical Engineering and School of Medicine, Stanford University, Stanford, CA, USA Anne Gieseler Molecular Pattern Recognition Research (MPRR) Group, Otto-von- Guericke-University Magdeburg Medical Faculty, Magdeburg, Germany Ve´ronique Giudicelli Laboratoire d’ImmunoGeńe´tique Molećulaire, Institut de Geńe´tique Humaine UPR 1142, Universite´ Montpellier 2, Montpellier, France Carole Goble School of Computer Science, University of Manchester, Manchester, UK Andre´s Fernando Gonza´lez Barrios Department of Chemical Engineering, Universidad de los Andes, Bogota´, Colombia Orland Gonzalez Institute for Bioinformatics, Ludwig-Maximilians-University Munich, Munich, Germany Sara Green Department of Physics and Astronomy, Centre for Science Studies, Aarhus University, Aarhus, Denmark Norbert Gretz Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany Manish Grover Department of Biochemistry, Indian Institute of Science, Banga- lore, Karnataka, India Daniel V. Guebel Department of Systems Biology and Bioinformatics, Institute of Computer Sciences, University of Rostock, Rostock, Germany Concettina Guerra Department Information Engineering, University of Padova, Padova, Italy xxvi Contributors

Shailendra K. Gupta Indian Institute of Toxicology Research (CSIR), Lucknow, India Pietro Hiram Guzzi Department of Experimental Medicine and Clinic, University Magna Gratia of Catanzaro, Catanzaro, Italy Gordon L. Hager Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Juergen Hahn Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA Udo Hahn Jena University Language and Information Engineering (JULIE) Labo- ratory, Friedrich-Schiller-University Jena, Jena, Germany Jorg€ Hakenberg Department of Computer Science and Department of Biomedical Informatics, Arizona State University, Tempe, AZ, USA Marta Halina Department of Philosophy and Science Studies Program, University of California, San Diego, San Diego, La Jolla, CA, USA David Harrison School of Medicine, University of St Andrews, St Andrews, Scotland, UK G. V. HarshaRani Neurobiology, National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India Jan Hasenauer Institute for Systems Theory and Automatic Control, University of Stuttgart, Stuttgart, Germany Haralambos Hatzikirou Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM, USA Michael Hauhs Ecological Modeling, University of Bayreuth, Bayreuth, Germany Winston Haynes Seattle Children’s Research Institute, Seattle, WA, USA Yongzheng He Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA Michael Hecker Department of Neurology, Institute of Immunology, University of Rostock, Rostock, Germany Jan G. Hengstler Leibniz Research Center for Working Environment and Human Factors, Dortmund, Germany Alexander Herbig Center for Bioinformatics Tubingen,€ Faculty of Science, University of Tubingen,€ Tubingen,€ Germany Georgina Herna´ndez-Montes Departamento de Medicina Molecular y Bioprocesos, Universidad Nacional Auto´noma de Me´xico, Cuernavaca, Morelos, Me´xico Roger Higdon Seattle Children’s Research Institute, Seattle, WA, USA Reyk Hillert Molecular Pattern Recognition Research (MPRR) Group, Otto-von- Guericke-University, Magdeburg, Germany Contributors xxvii

Stefan Hoehme Interdisciplinary Center for Bioinformatics, University of Leipzig, Leipzig, Germany

Carson Holt Department of Human Genetics, University of Utah, Salt Lake City, UT, USA

Vasant Honavar Center for Computational Intelligence, Learning, and Discovery, Computer Science, Iowa State University, Ames, IA, USA

Christian I. Hong Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Seok-Hee Hong School of IT, University of Sydney, Sydney, NSW, Australia Katsuhisa Horimoto Computational Biology Research Center, National Institute of Advanced Industrial and Science and Technology, Koto-ku, Tokyo, Japan

Anna Horva´th Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Budapest, Hungary

Pe´ter Horvatovich Department of Pharmacy, Analytical Biochemistry Research Group, University of Groningen, Groningen, The Netherlands

C. Vyvyan Howard Centre for Molecular Biosciences, University of Ulster, Coleraine, UK

Yufei Huang Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA Greehey Children’s Cancer Research Institute, University of Texas at Texas Health Science Center at San Antonio, San Antonio, TX, USA Department of Epidemiology and Biostatistics, University of Texas at Texas Health Science Center at San Antonio, San Antonio, TX, USA

Fuyan Hu Institute of Systems Biology, Shanghai University, Shanghai, China

Michael Hucka Computing and Mathematical Sciences, California Institute of Technology, Pasadena, CA, USA

Eyke Hullermeier€ Philipps-Universit€at Marburg, Marburg, Germany Andreas Huttemann€ Department of Philosophy, University of Cologne, Cologne, Germany

Philippe Huneman Institut d’Histoire et de Philosophie (IHPST), des Sciences et des Techniques, Universite´ Paris 1 Panthe´on-Sorbonne, Paris, France

Ying Hung Department of Statistics and Biostatistics, Rutgers University, Piscataway, NJ, USA

C. Anthony Hunt Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA

Akira Ishihama Department of Frontier Bioscience, Hosei University, Tokyo, Japan xxviii Contributors

Koichi Ito Graduate School of Frontier Sciences, University of Tokyo, Chiba, Tokyo, Japan Ravi Iyengar Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA James W. Jacobberger Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA Shruti Jain Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India Lars Juhl Jensen Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark Paul A. Jensen Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA Euna Jeong Institute of Medical Science, University of Tokyo, Tokyo, Japan Di Jia Department of Surgery/Harvard Medical School, Vascular Biology Program/ Children’s Hospital Boston, Boston, MA, USA Guangxu Jin Systems Medicine and Bioengineering, Bioengineering and Bioinfor- matics Program, The Methodist Hospital Research Institute, Weill Medical College, Cornell University, Houston, TX, USA Andrew R. Jones Institute of Integrative Biology, University of Liverpool, Liverpool, UK Bjorn€ Junker Systems Biology and Bioinformatic, Leibniz Institute of Plant Gene- tics and Crop Plant Research (IPK), OT Gatersleben, Stadt Seeland, Germany Nick Juty EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK Lars Kaderali Institute for Medical Informatics and Biometry Technical University, Dresden, Germany Marie I. Kaiser Department of Philosophy, University of Cologne, Cologne, Germany Aleksi Kallio CSC, IT Center for Science Ltd, Espoo, Finland Orsolya Kapuy Department of Biochemistry, Oxford Centre for Integrative Sys- tems Biology, University of Oxford, Oxford, UK Mahendra Kavdia Department of Biomedical Engineering, Wayne State University, Detroit, MI, USA Gota Kawai Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba, Japan Junya Kawauchi Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan Sarah M. Keating EMBL -European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK Contributors xxix

C. Maria Keet KRDB Research Centre, Free University of Bozen-Bolzano, Bolzano, Italy Douglas Bruce Kell School of Chemistry and Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK Evelyn Fox Keller Massachusetts Institute of Technology (MIT), Cambridge, MA, USA Melissa L. Kemp The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA Stefan Kempa Integrative Metabolomics and Proteomics, BIMSB (Berlin Institute for Medical Systems Biology), Berlin, Germany Noel Kennedy School of Biomedical Sciences, University of Ulster, Coleraine, UK Carsten Kettner Beilstein-Institut zur Forderung€ der Chemischen Wissenschaften, Frankfurt am Main, Germany Melissa Key Center for Computational Diagnostics, Indianapolis, IN, USA Michael Khan Department of Biological Science, Biomedical Research Institute, University of Warwick, Coventry, UK Javed Mohammed Khan Department of Chemistry and Biomolecular Sciences and ARC Center of Excellence in Bioinformatics, Macquarie University, Sydney, NSW, Australia Narsis Aftab Kiani ViroQuant Research Group Modeling, BioQuant, University of Heidelberg, Heidelberg, Germany Andrzej M. Kierzek Division of Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK Jan T. Kim School of Computing Sciences, University of East Anglia, Norwich, Norfolk, UK Jin-Dong Kim Database Center for Life Science, Tokyo, Japan Angelika Kimmig Departement Computerwetenschappen, Katholieke Universiteit Leuven, Heverlee, Belgium John R. King School of Mathematical Sciences, University of Nottingham, Nottingham, UK Alexandros Kiparissides Biological Systems Engineering Laboratory, Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College, London, UK Max Kistler IHPST, Universite´ Paris 1 Panthe´on-Sorbonne, Paris, France Shigetaka Kitajima Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan David Klatzmann Immunology-Immunopathology-Immunotherapy, UPMC Uni- versity Paris 06, UMR7211, CNRS, UMR7211, INSERM, U959, Paris, France xxx Contributors

Edda Klipp Theoretical Biophysics, Humboldt-Universit€at zu Berlin, Berlin, Germany Dirk Koczan Department of Neurology, Institute of Immunology, University of Rostock, Rostock, Germany Tetsuro Kokubo Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University, Yokohama, Kanagawa, Japan Michal Kola´rˇ Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic Eugene Kolker Bioinformatics and High–throughput Analysis Laboratory, Seattle Children’s Research Institute, Seattle, WA, USA Departments of Biomedical Informatics and Medical Education and Pediatrics, University of Washington, Seattle, WA, USA Arun S. Konagurthu Clayton School of Information Technology, Monash University, Clayton, VIC, Australia K. K. Koutroumpas Automatic Control Laboratory, ETH Zurich, Zurich, Switzerland Martin Krallinger Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain Clemens Kreutz Institute for Physics, Freiburger Center for Data Analysis and Modeling (FDM), University of Freiburg, Freiburg, Germany Ulrich Krohs Department of Philosophy, University of Munster,€ Munster,€ Germany Andreas Krusche Molecular Pattern Recognition Research (MPRR) Group, Otto-von-Guericke-University, Magdeburg, Germany Kai Kruse MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK Martin Kuiper Department of Biology, Systems Biology Group, Norwegian University of Science and Technology, Trondheim, Norway Sanjeev Kumar BioCOS Life Sciences Private Limited, Bangalore, Karnataka, India Manfred Kunz Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig, Germany Hitoshi Kurumizaka Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan Xin Lai Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, Rostock, Germany Camille Laibe EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK Tai Ning Lam Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA Contributors xxxi

Tze Hau Lam Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Christoph H. Lampert IST Austria, Klosterneuburg, Austria Qizong Lao Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Sneh Lata Cold Spring Harbor Laboratory, Genome Research Center, Woodbury, NY, USA Reinhard Laubenbacher Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA, USA Sang Yup Lee Department of Chemical and Biomolecular Engineering and Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Tae Lee School of Biology and School of Physics, Georgia Institute of Technology, Atlanta, GA, USA Yun Lee The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA Marie-Paule Lefranc Laboratoire d’ImmunoGeńe´tique Molećulaire, Institut de Geńe´tique Humaine UPR 1142, Universite´ Montpellier 2, Montpellier, France Jinzhi Lei Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University of Beijing, Beijing, China Florian Leitner Structural Biology and BioComputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain Sabina Leonelli ESRC Centre for Genomics in Society, University of Exeter, Exeter, Devon, UK Ulf Leser Institute for Computer Science, Humboldt-Universit€at zu Berlin, Berlin, Germany Arthur M. Lesk Department of Biochemistry and Molecular Biology, and Huck Institutes of Genomics, Proteomics, and Bioinformatics, Pennsylvania State Univer- sity, University Park, PA, USA Wentian Li The Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, NY, USA Yan Li Department of Pediatrics, Indiana University School of Medicine, Indiana- polis, IN, USA Zhenping Li School of Information, Beijing Wuzi University, Beijing, China Wolfram Liebermeister Institut fur€ Biochemie, Charite´ - Universit€atsmedizin Berlin, Berlin, Germany Frank Lin Centre for Health Informatics, Australian Institute for Health Innovation, University of New South Wales, Sydney, NSW, Australia Ke-Qin Liu Institute of Systems Biology, Shanghai University, Shanghai, China xxxii Contributors

Xiaojun Liu Internal Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China Xiaoping Liu Institute of Systems Biology, Shanghai University, Shanghai, China Zhi-Ping Liu Key Laboratory of Systems Biology, Shanghai Institutes for Biolo- gical Sciences, Chinese Academy of Sciences, Shanghai, China Catherine M. Lloyd Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Luca Lombardi Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy Isaac F. Lo´pez-Moyado Center for Genomic Sciences-UNAM, Universidad Nacional Autonoma de Mexico, Cuernavaca (Morelos), Mexico Jingky Lozano-Kuhne€ Department of Public Health, University of Oxford, Oxford, UK Long Jason Lu Division of Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, Cincinnati, OH, USA John Lygeros Automatic Control Laboratory, ETH Zurich, Zurich, Switzerland Zoi Lygerou School of Medicine, Laboratory of General Biology, University of Patras, Patras, Greece Shuangge Ma Yale School of Public Health, Yale University, New Haven, CT, USA Hong-Wu Ma School of Informatics, University of Edinburgh, Edinburgh, UK Lars Malmstrom€ Institute of Molecular Systems Biology IMSB, ETH Zurich, Zurich, Switzerland Marcos Malumbres Spanish National Cancer Research Centre (CNIO), Madrid, Spain Sebastian Mana-Capelli Department of Molecular Genetics and Microbiology, University of Massachusetts, Worcester, MA, USA Athanasios Mantalaris Biological Systems Engineering Laboratory, Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College, London, UK Samuel Marguerat Department of Genetics, Evolution and Environment and UCL Cancer Institute, University College London, London, UK Alberto Marin-Sanguino Faculty of Mechanical Engineering, Specialty Division for Systems Biotechnology, Technical University Munich, Garching, Germany Jose´ Antonio Martıńez Department of Computer Architecture and Electronics, University of Almerıá, Almerıá, Spain Elio Mattia Centre for Systems Chemistry, Stratingh Institute for Chemistry, Rijksuniversiteit Groningen, Groningen, The Netherlands Contributors xxxiii

Dannel McCollum Department of Molecular Genetics and Microbiology, University of Massachusetts, Worcester, MA, USA

Johnjoe McFadden Division of Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

Barry McMullin The Rince Institute, Dublin City University, Dublin, Ireland

Hendrik Mehlhorn Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Stadt Seeland, Germany

Francisco Melo Pontiﬁcia Universidad Cato´lica de Chile, Santiago, Chile Millennium Institute on Immunology and Immunotherapy, Santiago, Chile

Nuno D. Mendes Knowledge Discovery and Bioinformatics (KDBIO) Group, INESC–ID, Lisbon, Portugal Network Modelling Group, Instituto Gulbenkian de Cieˆncia (IGC), Oeiras, Portugal

Eduardo Mendoza Department of Computer Science, University of the Philippines Diliman, Quezon City, Philippines

Donna L. Mendrick Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA

Jia Meng Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA

Carsten Mente Center for Information Services and High Performance Computing (ZIH), Technical University Dresden, Dresden, Germany

Ivan Merelli Institute for Biomedical Technologies – CNR (Consiglio Nazionale delle Ricerche), Segrate, Milan, Italy

Marco Mernberger Philipps-Universit€at Marburg, Marburg, Germany

Luciano Milanesi Institute for Biomedical Technologies – CNR (Consiglio Nazionale delle Ricerche), Segrate, Milan, Italy

Andrew K. Miller Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand

Alex Mirnezami Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK Cancer Research UK Centre, Cancer Sciences Division, School of Medicine, Southampton General Hospital, Southampton, UK

Vladimir Mironov Department of Biology, Systems Biology Group, Norwegian University of Science and Technology, Trondheim, Norway

Satoru Miyano Institute of Medical Science, University of Tokyo, Tokyo, Japan

Rau´l Montan˜ez Institut de Biologia Evolutiva CSIC-UPF (Universitat Pompoi Fabra), Barcelona, Spain xxxiv Contributors

Emily A. Moon Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA Ion Moraru R.D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT, USA Alvaro Moreno Department of Logic and Philosophy of Science, University of the Basque Country, San Sebastian, Spain Rafael Moreno-Sańchez Department of Biochemistry, National Institute for Cardiology “Ignacio Cha´vez”, Mexico City, Mexico Sergio Moreno Instituto de Biologıá Molecular y Celular del Cańcer, CSIC/ Universidad de Salamanca, Salamanca, Spain Hisao Moriya Okayama University Research Core for Interdisciplinary Sciences, Kita-ku, Okayama, Japan Ettore Mosca Institute for Biomedical Technologies – CNR (Consiglio Nazionale delle Ricerche), Segrate, Milan, Italy Marsha A. Moses Department of Surgery/Harvard Medical School, Vascular Biology Program/Children’s Hospital Boston, Boston, MA, USA Lenny Moss Department of Sociology and Philosophy, University of Exeter, Exeter, Devon, UK Matteo Mossio IAS-Research Philosophy of Biology Group, Department of Logic and Philosophy of Science, University of the Basque Country (UPV/EHU), Donostia – San Sebastian, Spain Sumanta Mukherjee Bioinformatics Centre, Indian Institute of Science, Bangalore, Karnataka, India Ivan Mura The Microsoft Research - University of Trento Centre for Computa- tional and Systems Biology, Trento, Italy Katsuhiko S. Murakami Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA Yota Murakami Department of Chemistry, Hokkaido University, Sapporo, Japan Mark A. Musen Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA Marco Muzi-Falconi Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita` di Milano, Milan, Italy Rajeswara Babu Mythri Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India Jose C. Nacher Department of Information Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan Haroon Naeem Institute for Bioinformatics, Ludwig-Maximilians-University Munich, Munich, Germany Masao Nagasaki Institute of Medical Science, University of Tokyo, Tokyo, Japan Contributors xxxv

Grzegorz Nalepa Department of Pediatrics, Section of Pediatric Hematology- Oncology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA Nobukazu Nameki Gunma University, Kiryu, Japan Jeyakumar Natarajan Data Mining and Text Mining Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore, India Tim W. Nattkemper Biodata Mining Group, Faculty of Technology, Bielefeld University, Bielefeld, Germany Chrystopher L. Nehaniv Royal Society/Wolfson Bio Computation Research Laboratory, School of Computer Science, University of Hertfordshire, Hatﬁeld, UK Patrick Nelson CCMB 2017 Palmer Commons, University of Michigan, Ann Arbor, MI, USA Goran Nenadic Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK David P. Nickerson Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Poul M. Nielsen Department of Engineering Science, University of Auckland, Auckland, New Zealand Kay Nieselt Center for Bioinformatics Tubingen,€ Faculty of Science, University of Tubingen,€ Tubingen,€ Germany Siegfried Nijssen Katholieke Universiteit, Leuven, Belgium Svetoslav Nikolov Institute of Mechanics and Biomechanics-BAS, Bulgarian Academy of Science, Soﬁa, Bulgaria Chris J. Norbury Sir William Dunn School of Pathology, University of Oxford, Oxford, UK Be´la Nova´k Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK Nicolas le Nove`re EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, UK Geoff Nunns Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Michael F. Ochs Department of Oncology, Johns Hopkins University, Baltimore, MD, USA Maureen A. O’Malley Department of Philosophy, University of Sydney, Sydney, NSW, Australia Sandra Orchard EMBL Outstation, European Bioinformatics Institute, Hinxton, Cambridge, UK Gerard J. Ostheimer Department of Agriculture, Washington, DC, USA xxxvi Contributors

Casey L. Overby Medical Education and Biomedical Informatics, University of Washington School of Medicine, Seattle, WA, USA Brigitte Katrin Paap Department of Neurology, Institute of Immunology, Univer- sity of Rostock, Rostock, Germany Graham Packham Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Southampton University Hospital NHS Trust, Southampton, UK Niall Palfreyman Biotechnology and Bioinformatics, Weihenstephan-Triesdorf University of Applied Science, Freising, Germany Alida Palmisano Department of Biological Sciences and Department of Computer Science, Department of Biological Sciences Virginia Tech, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA Luigi Palopoli Dipartimento di Elettronica, Informatica e Sistemistica Universita` della Calabria, Rende, Italy Paolo De Paoli Centro di Riferimento Oncologico (CRO) – IRCCS, Aviano, PN, Italy Antonis Papachristodoulou Department of Engineering Science, University of Oxford, Oxford, UK Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK Jason A. Papin Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA Sunwon Park Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Chaitali Paul G.N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India Shayn M. Peirce Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA Luiz O. F. Penalva Department of Cellular and Structural Biology, Greehey Children’s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA Livia Pe´rez-Hidalgo Instituto de Biologıá Molecular y Celular del Cańcer, CSIC/ Universidad de Salamanca, Salamanca, Spain Ernesto Perez-Rueda Departamento de Ingenier´ıa Celular y Biocata´lisis, Instituto de Biotecnologia, Universidad Nacional Autono´ma de Me´xico, Cuernavaca, More- los, Mexico Nikolai Petrovsky Department of Endocrinology, Flinders Medical Centre/Flinders University, Adelaide, Australia Steve R. Pettifer Faculty of Life Sciences and School of Computer Science, University of Manchester, Manchester, UK Andre´s Mauricio Pinzoń Velasco Department of Systems Engineering, Universidad Jorge Tadeo Lozano, Bogota´, Colombia Contributors xxxvii

Efstratios Pistikopoulos Biological Systems Engineering Laboratory, Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College, London, UK

Conrad Plake Biotechnology Center (BIOTEC), Technische Universit€at Dresden, Dresden, Germany

Hannes Planatscher Natural and Medical Sciences Institute at the University of Tuebingen, Reutlingen, Germany

Paolo Plevani Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita` di Milano, Milan, Italy

Daniel Polani Adaptive Systems Research Group, School of Computer Science, University of Hertfordshire, Hatﬁeld, UK

Joseph R. Pomerening Department of Biology, Indiana University, Bloomington, IN, USA

Ranjan K. Pradhan Department of Physiology, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA

Karyala Prashanthi Bioinformatics Centre, Indian Institute of Science, Bangalore, Karnataka, India

Corrado Priami Microsoft Research-University of Trento Centre for Computa- tional and Systems Biology and DISI, University of Trento, Povo, Trento, Italy

Ela Pustulka-Hunt GS SystemsX, ETH Zurich, Zurich, Switzerland

Sampo Pyysalo Department of Computer Science, University of Tokyo, Tokyo, Japan

Zhen Qi The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA

Hong Qian Department of Applied Mathematics, University of Washington, Seattle, WA, USA

Yu-Qing Qiu Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China

Novi Quadrianto SML-NICTA and RSISE-ANU, Canberra, ACT, Australia

Andreas Quandt Institute of Molecular Systems Biology IMSB, ETH Zurich, Zurich, Switzerland

Vito Quaranta The Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

Anna Ra´cz-Mo´nus Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Budapest, Hungary

Gajendra Raghava Bioinformatics Centre, Institute of Microbial Technology, Chandigarh, Chandigarh, India

Kalpana Raja Data Mining and Text Mining Laboratory, Department of Bioinfor- matics, Bharathiar University, Coimbatore, India xxxviii Contributors

Meghna Rajvanshi Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India Jorge Mario Gomez Ramirez Department of Chemical Engineering, Universidad de los Andes, Bogota´, Colombia Jan Ramon Declarative Languages and Artificial Intelligence Group, Katholieke Universiteit Leuven, Leuven, Belgium Shoba Ranganathan Department of Chemistry and Biomolecular Sciences and ARC Center of Excellence in Bioinformatics, Macquarie University, Sydney, NSW, Australia Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Rajni Rani Molecular Immunogenetics Group, National Institute of Immunology, New Delhi, Delhi, India M. R. Satyanarayana Rao Chromatin Biology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Banga- lore, Karnataka, India Andreas Raue Institute for Physics, University of Freiburg, Freiburg, Germany Dietrich Rebholz-Schuhmann European Bioinformatics Institute, Hinxton, UK Ee chee Ren Laboratory of Immunogenetics and Viral Host-Pathogen Genomics, Singapore Immunology Network, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Xianwen Ren Key Laboratory of Systems Biology of Pathogens, Ministry of Health, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Osbaldo Resendis-Antonio Center for Genomics Sciences-UNAM, Universidad Nacional Autono´ma de Me´xico, Cuernavaca, Morelos, Mexico Silvia Restrepo Department of Biological Sciences, Universidad de los Andes, Bogota´, Colombia Steven D. Rhodes School of Medicine, Indiana University, Indianapolis, IN, USA Robert C. Richardson Department of Philosophy, University of Cincinnati, Cincinnati, OH, USA Gregory Riddick Neuro-Oncology Branch, National Cancer Institute, Bethesda, MD, USA Andrea Rocco Division of Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK Carlos Rodrı´guez-Caso Complex Systems Laboratory, University Pompeu Fabra, Barcelona, Spain Domingo Rodrı´guez-Baena School of Engineering, Pablo de Olavide University, Escuela Politećnica Superior, Seville, Spain Contributors xxxix

Maria Rodriguez-Fernandez Department of Chemical Engineering, Institute for Collaborative Biotechnologies, University of California, Santa Barbara, CA, USA M. Carmen Romano Institute for Complex Systems and Mathematical Biology, University of Aberdeen, Aberdeen, UK Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK Simona E. Rombo Istituto di Calcolo e Reti ad Alte Prestazioni, Consiglio Nazionale delle Ricerche, Rende (CS), Italy Dipartimento di Elettronica, Informatica e Sistemistica, Universita` della Calabria, Rende, Italy Ricardo Cruz-Herrera del Rosario Genome Institute of Singapore, Singapore, Singapore Sigrid Rouam Universite´ Paris-Sud, Villejuif, France Jianhua Ruan Department of Computer Science, University of Texas at San Antonio, San Antonio, TX, USA Fabian Rudolf Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland Oliver Ruebenacker Center for Cell Analysis and Modeling, University of Con- necticut Health Center, Farmington, CT, USA Kepa Ruiz-Mirazo Department Logic and Philosophy of Science, University of the Basque Country, Donostia – San Sebastia´n, Spain Biophysics Unit (CSIC–UPV/EHU), University of the Basque Country, Leioa, Spain Ann E. Rundell Biomedical Engineering, Purdue University, West Lafayette, IN, USA Mika O. Ruonala NeuroToponomics Group, Center for Membrane Proteomics Campus Riedberg, Goethe University of Frankfurt, Frankfurt, Germany Emma Saavedra Department of Biochemistry, National Institute for Cardiology “Ignacio Cha´vez”, Mexico City, Mexico Sudipto Saha School of Medicine, Center for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH, USA Kazuki Saito Graduate School of Frontier Sciences, University of Tokyo, Chiba, Tokyo, Japan Shigeru Saito Infocom Corporation, Tokyo, Japan Taiichi Sakamoto Chiba Institute of Technology, Narashino, Japan Kishore R. Sakharkar Infectious Diseases Cluster, Universiti Sains Malaysia, Pulau Pinang, Malaysia Meena K. Sakharkar Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Ibaraki, Japan Alberto Sanguino Specialty Division for Systems Biotechnology, Technical University of Munich, Garching, Germany xl Contributors

Giuliana Di Santo Dipartimento di Elettronica, Informatica e Sistemistica Universita` della Calabria, Rende, Italy

Akinori Sarai Department of Bioscience and Bioinformatics, Kyushu Institute of Technology (KIT), Iizuka, Japan

Kazunori Sasaki Human Metabolome Technologies Inc., Tsuruoka, Yamagata, Japan

Masamitsu Sato Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo–ku, Tokyo, Japan PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan

Emre Sayan Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Southampton University Hospital NHS Trust, Southampton, UK

Jutta Schickore Department of History and Philosophy of Science, Indiana Uni- versity, Bloomington, IN, USA

Tamar Schlick Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, New York, NY, USA

Oliver Schmidt School of Biomedical Sciences, University of Ulster, Coleraine, UK

Bernhard Schmierer Department of Biochemistry, Oxford Centre for Integrative Systems Biology (OCISB), University of Oxford, Oxford, UK

Ulf Schmitz Department of Systems Biology and Bioinformatics, Institute of Com- puter Science, University of Rostock, Rostock, Germany

Christian Schonbach€ Department of Bioscience and Bioinformatics, Kyushu Insti- tute of Technology, Iizuka, Fukuoka, Japan

Falk Schreiber Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), OT Gatersleben, Stadt Seeland, Germany Martin Luther University Halle–Wittenberg, Halle, Germany

Walter Schubert Molecular Pattern Recognition Research (MPRR) Group, Otto–von–Guericke University Magdeburg, Magdeburg, Germany Chinese Academy of Science and Max Planck Society (CAS–MPG) Partner Institute for Computational Biology (PICB), Shanghai, China Human Toponome Project, ToposNomos Ltd, Munich, Germany

Jean-Marc Schwartz Manchester Institute of Biotechnology, Faculty of Life Sciences, University of Manchester, Manchester, UK

Masayuki Seki Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan

Rituparna Sen G.N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India

Toshiya Senda Biomedicinal Information Research Centre (BIRC), National Insti- tute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan Contributors xli

Ab Rauf Shah G.N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India

Jagesh Shah Department of Systems Biology, Harvard Medical School and Renal Division, Brigham and Women’s Hospital, Boston, MA, USA

Deepak Sharma Translational Health Science and Technology Institute, Gurgaon, India

Nobuo Shimamoto Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan

Richard Simon Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland, USA

Harpreet Singh Computational Biology Service Unit, Cornell University, Ithaca, NY, USA Biomedical Informatics Centre, Indian Council of Medical Research, New Delhi, India

Adrien Six Immunology-Immunopathology-Immunotherapy, UPMC University Paris 06, UMR7211, CNRS, UMR7211, INSERM, U959, Paris, France

Jan M. Skotheim Department of Biology, Stanford University School of Medicine, Stanford, CA, USA

Brian D. Sleeman School of Mathematics, University of Leeds, Leeds, UK

Andrew D. Smith Molecular and Computational Biology Section, Division of Biological Sciences, University of Southern California, Los Angeles, CA, USA

Jacky L. Snoep Department of Biochemistry, Stellenbosch University, Matieland, South Africa Manchester Institute for Biotechnology, University of Manchester, Manchester, UK Molecular Cell Physiology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Tatsuhiko Someya University of Tsukuba, Tsukuba, Japan

Pramod R. Somvanshi Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India

Carlos Sonnenschein Department of Anatomy and Cellular Biology, Tufts Univer- sity School of Medicine, Boston, MA, USA

Ana M. Soto Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA

Sandro J. de Souza Ludwig Institute for Cancer Research, Sao Paolo, Brazil

Irena Spasic´ School of Computer Science and Informatics, Cardiff University, Cardiff, UK

Josef Spidlen Terry Fox Laboratory, BC Cancer Agency, BC Cancer Research Centre, Vancouver, BC, Canada xlii Contributors

Rahul Sreekumar Cancer Research UK Centre, University of Southampton Cancer Sciences Division, Southampton University Hospital NHS Trust, Southampton, UK Ramachandran Srinivasan G.N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India Gesa Staats Centre for Molecular Biosciences, University of Ulster, Coleraine, UK Larissa Stanberry Bioinformatics and High-throughput Analysis Laboratory, Seattle Children’s Research Institute, Seattle, WA, USA Ian Stansﬁeld Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK Jorn€ Starruß Centre for High Performance Computing (ZIH), Technical University Dresden, Dresden, Germany Karl Staser Departments of Pediatrics and Biochemistry, Indiana University School of Medicine, Indianapolis, IN, USA Christiana Staudinger Department of Molecular Systems Biology, University of Vienna, Vienna, Austria Joerg Stelling Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland Achim Stephan Institute of Cognitive Science, University of Osnabruck,€ Osnabruck,€ Germany Susan Stepney Department of Computer Science, University of York, York, UK Carsten Sticht Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany Beatriz Stransky Universidade Federal do ABC, Santo Andre, Brazil Suresh Subramani Data Mining and Text Mining Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore, India Chenglei Sun Institute of Systems Biology, Shanghai University, Shanghai, Shanghai, China Xiaojuan Sun Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University of Beijing, Beijing, China Myong-Hee Sung Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Avadhesha Surolia Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India A´ kos Sveiczer Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Budapest, Hungary Martin Swain Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth, Ceredigion, UK Hideaki Tagami Graduate School of Natural Sciences, Nagoya City University, Nagoya, Aichi, Japan Contributors xliii

Kan Tanaka Chemical Resources Laboratory, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan Jijun Tang Department of Computer Science and Engineering, University of South Carolina, Columbia, SC, USA Luis Tari Pharma Early Development Informatics, Hoffmann-La Roche Inc., Nutley, NJ, USA Utpal Tatu Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, India Giorgio Terracina Dipartimento di Matematica, Universita` della Calabria, Rende, Italy Madhan Thamilarasan Department of Neurology, Institute of Immunology, University of Rostock, Rostock, Germany Denis Thieffry IBENS - UMR ENS - CNRS 8197 - INSERM 1024, Paris, France Ve´ronique Thomas-Vaslin Immunology-Immunopathology-Immunotherapy, UPMC University Paris 06, UMR7211, CNRS, UMR7211, INSERM, U959, Paris, France Paul Thompson School of Biomedical Sciences, University of Ulster, Coleraine, UK Jens Timmer Institute for Physics, University of Freiburg, Freiburg, Germany BIOSS Centre for Biological Signalling Studies and Freiburg Institute for Advanced Studies (FRIAS), Freiburg, Germany Department of Clinical and Experimental Medicine, Linkoping€ University, Linkoping,€ Sweden Jared Toettcher University of California, San Francisco, CA, USA Joo Chuan Tong Data Mining Department, Institute for Infocomm Research, Singapore, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Weida Tong Division of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA Ne´stor V. Torres Department of Biochemistry and Molecular Biology, University of La Laguna, San Cristo´bal de La Laguna, Islas Canarias, Tenerife, Spain Giuseppe Tradigo Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy Baltasar Tranco´n y Widemann Ecological Modelling, University of Bayreuth, Bayreuth, Germany Guy Tsafnat Centre for Health Informatics, Australian Institute for Health Innovation, University of New South Wales, Sydney, NSW, Australia Krasimira Tsaneva-Atanasova Department of Engineering Mathematics, University of Bristol, Bristol, UK xliv Contributors

Nam-Kiu Tsing Advanced Modeling and Applied Computing Laboratory, Department of Mathematics, University of Hong Kong, Hong Kong, China Jarno Tuimala Finnish Red Cross Blood Service, Helsinki, Finland Tama´s Turańyi Institute of Chemistry, Eotv€ os€ University (ELTE), Budapest, Hungary John J. Tyson Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA Darren Tyson Vanderbilt University, Nashville, TN, USA Jon Umerez IAS-Research Philosophy of Biology Group, Department of Logic and Philosophy of Science, University of the Basque Country (UPV/EHU), Donostia – San Sebastian, Spain Leosˇ Shivaya Vala´sˇek Laboratory of Regulation of Gene Expression, Institute of Microbiology AVCR, Prague, Czech Republic Shireen Vali Cell Works Group Inc., Bangalore, India Justin N. Vaughn Department of Biochemistry, Cellular, and Molecular Biology, University of Tennessee, Knoxville, USA Marquis P. Vawter Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA Fransisco Va´zquez Department of Computer Architecture and Electronics, Univer- sity of Almerıá, Almerıá, Spain Kann Vearasilp Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, Rostock, Germany Nubia Velasco Department of Industrial Engineering, Universidad de los Andes, Bogota´, Colombia Pierangelo Veltri Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy Kareenhalli V. Venkatesh Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India Celine Vens Department of Computer Science, Katholieke Universiteit Leuven, Leuven, Belgium Julio Vera Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, Rostock, Germany Rajni Verma G.N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, Delhi, India Karin Verspoor Victoria Research Laboratory, National ICT Australia, University of Melbourne, Melbourne, VIC, Australia Center for Computational Pharmacology, University of Colorado, Aurora, CO, USA Basilio Vescio Department of Clinical and Experimental Medicine, Magne Graecia University of Catanzaro, Catanzaro, Italy Contributors xlv

Kalyan C. Vinnakota Computational Bioengineering Group, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA P. K. Vinod Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK Rosella Visintin IEO, European Institute of Oncology, Milan, Italy Olga Vitek Department of Statistics, Department of Computer Science, Purdue University, West Lafayette, IN, USA Juan Antonio Vizcaı´no EMBL Outstation, European Bioinformatics Institute (EBI), European Molecular Biology Laboratory Wellcome Trust Genome Campus, Hinxton, Cambridge, UK Dat T. Vo Department of Cellular and Structural Biology, Greehey Children’s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA Eberhard O. Voit The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA Albrecht G. von Arnim Department of Biochemistry, Cellular, and Molecular Biology and Graduate Program in Genome Science and Technology, University of Tennessee, Knoxville, USA Anja Voss-Bohme€ Center for Information Services and High Performance Com- puting (ZIH), Technical University Dresden, Dresden, Germany Christine Waddington MOAC/University of Warwick, Coventry, UK Andreas Wagner Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland Steffen Waldherr Institute for Systems Theory and Automatic Control, University of Stuttgart, Stuttgart, Germany Feng-Sheng Wang Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan Haiying Wang School of Computing and Mathematics, Computer Science Research Institute, University of Ulster, Jordanstown, UK Jiguang Wang Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, Beijing, China Lin Wang School of Computer Science and Information Engineering, Tianjin University of Science and Technology, Tianjin, China Rui-Sheng Wang Department of Physics, Pennsylvania State University, Univer- sity Park, PA, USA Ruiqi Wang Institute of Systems Biology, Shanghai University, Shanghai, China Yong Wang Academy of Mathematics and Systems Sciences, Chinese Academy of Sciences, Beijing, China Zhihui Wang Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA xlvi Contributors

Lin Wanglin School of Computer Science and Information Engineering, Tianjin University of Science and Technology, Tianjin, China Eric Werner Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK Department of Computer Science, University of Oxford, Oxford, UK Oxford Advanced Research Foundation, Fort Myers, FL, USA Stefanie Wienkoop Department of Molecular Systems Biology, University of Vienna, Vienna, Austria Peter Wilkinson Vaccine and Gene Therapy Institute, Port St. Lucie, FL, USA Jana Wolf Mathematical Modelling of Cellular Processes, MDC Max Delbruck€ Center for Molecular Medicine, Berlin, Germany Katy Wolstencroft School of Computer Science, University of Manchester, Manchester, UK Arno Wouters Department of Philosophy, Erasmus University Rotterdam, Rotterdam, The Netherlands Xiaohua Wu Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA Kejia Xu Institute of Systems Biology, Shanghai University, Shanghai, China Yuki Yamaguchi Tokyo Institute of Technology, Graduate School of Bioscience and Biotechnology, Yokohama, Japan Feng-Chun Yang Departments of Pediatrics, Herman B Wells Center for Pediatric Research, School of Medicine, Indiana University, Indianapolis, IN, USA Guang Yao Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA Weiwei Yin Department of Biomedical Engineering, Georgia Institute of Technol- ogy and Emory University, Atlanta, GA, USA Elizabeth Yohannes Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA Lingchong You Biomedical Engineering Department, Duke University, Durham, NC, USA Tao You Computational Biology, Innovative Medicines, AstraZeneca, Macclesﬁeld, Cheshire, UK Tommy Yu Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand Choamun Yun Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Hongseok Yun Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Contributors xlvii

Judit Za´mborszky The Microsoft Research - University of Trento Centre for Computational and Systems Biology, CoSBi, Trento, Italy An-Ping Zeng Institute of Bioprocess and Biosystems, Technical University Hamburg-Harburg, Hamburg, Germany Yi Zeng Department of Pediatrics, University of Arizona, Tucson, AZ, USA Marie Lisandra Zepeda-Mendoza Center for Genomics Sciences-UNAM, Universidad Nacional Auto´noma de Me´xico, Cuernavaca, Morelos, Mexico Uwe Klaus Zettl Department of Neurology, Institute of Immunology, University of Rostock, Rostock, Germany Junhua Zhang Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China Key Laboratory of Random Complex Structures and Data Science, Chinese Academy of Sciences, Beijing, China National Center for Mathematics and Interdisciplinary Sciences, Chinese Academy of Sciences, Beijing, China Minlu Zhang Department of Computer Science, University of Cincinnati, Cincinnati, OH, USA Shihua Zhang National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China Shu-Qin Zhang School of Mathematical Sciences, Fudan University, Shanghai, China Xiujun Zhang Institute of System Biology, Shanghai University, Shanghai, China Yan Zhang Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Zhong-Yuan Zhang School of Statistics, Central University of Finance and Eco- nomics, Beijing, China Shan Zhao Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY, USA Xing-Ming Zhao Institute of System Biology, Shanghai University, Shanghai, China Yingdong Zhao Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland, USA Huiru Zheng School of Computing and Mathematics, Computer Science Research Institute, University of Ulster, Jordanstown, UK Tianshou Zhou School of Mathematics and Computational Sciences, Sun Yet-Sen University, Guangzhou, Guangdong, China