Complex Systems and Computational Biology Approaches to Acute In Ammation Complex Systems and Computational Biology Approaches to Acute Infl Ammation
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Yoram Vodovotz · Gary An Editors Complex Systems and Computational Biology Approaches to Acute In ammation Complex Systems and Computational Biology Approaches to Acute Infl ammation Yoram Vodovotz • Gary An Editors Complex Systems and Computational Biology Approaches to Acute Infl ammation Editors Yoram Vodovotz Gary An Department of Surgery Department of Surgery University of Pittsburgh University of Chicago Pittsburgh , PA , USA Chicago , IL , USA ISBN 978-1-4614-8007-5 ISBN 978-1-4614-8008-2 (eBook) DOI 10.1007/978-1-4614-8008-2 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013945078 © Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms 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 specifi cally 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 specifi c 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 Science+Business Media (www.springer.com) Preface We are now standing at the cusp of systems-based understanding of the processes that underlie, drive, and control the acute infl ammatory response. Based on decades of painstaking progress, mostly driven by the reductionist methods that have served science well for hundreds of years, this new systems approach is poised to redefi ne how we approach diagnosis and therapy for sepsis/infection, trauma, and wound healing. The development of systems and computational biology over the past decade has brought a new understanding, new methods, and new terminology to the forefront of the biomedical enterprise. These new tools and new understanding have begun to yield insights into basic biological mechanisms. What has lagged has been a clear understanding of how sys- tems and computational biology could be applied systematically to change clinical practice. Indeed, we have not yet fully leveraged the power of computational and systems biology. There is currently no fully rational, computationally driven, pipe- line for drug discovery, clinical trials, “smart” diagnostics, and patient-specifi c ther- apy driven by computational modeling (i.e., Translational Systems Biology). However, we are at, or near, an infl ection point in this transition from reductionism to systems approaches applied clinically. Translational Systems Biology as a concept was formulated in an attempt to give initial defi nitions and directions to the biomedi- cal community. A decade of Translational Systems Biology has resulted in increas- ingly realistic computational models that can recapitulate infl ammation at the cellular, small animal, large animal, and human levels. As such, Translational Systems Biology is at an infl ection point between early studies subjected to intense scrutiny and, to a degree, resistance from the research community vs. widespread adoption. This book presents a snapshot of this infl ection point. Pittsburgh , PA , USA Yoram Vodovotz Chicago , IL , USA Gary An v Contents 1 An Overview of the Translational Dilemma and the Need for Translational Systems Biology of Infl ammation ............................ 1 Yoram Vodovotz and Gary An Part I Complex Systems Methods and Applications 2 Translational Equation-Based Modeling .............................................. 11 Gilles Clermont 3 Agent-Based Modeling in Translational Systems Biology ................... 29 Scott Christley and Gary An 4 Analysis of Heart Rate Variability ........................................................ 51 Patrick R. Norris 5 Analysis of Ventilatory Pattern Variability........................................... 79 Thomas E. Dick, Rishi R. Dhingra, Yee-Hsee Hsieh, Mikkel Fishman, Farhad Kaffashi, Kenneth A. Loparo, Christopher G. Wilson, and Frank J. Jacono Part II Translational Modeling of Sepsis and Trauma 6 Disorder of Systemic Infl ammation in Sepsis and Trauma: A Systems Perspective ........................................................................... 103 Kent R. Zettel II and Timothy R. Billiar 7 Multiscale Equation-Based Models: Insights for Infl ammation and Physiological Variability ................................................................. 125 Jeremy D. Scheff, Steve E. Calvano, and Ioannis P. Androulakis vii viii Contents 8 Integrating Data-Driven and Mechanistic Models of the Infl ammatory Response in Sepsis and Trauma ........................ 143 Nabil Azhar, Qi Mi, Cordelia Ziraldo, Marius Buliga, Gregory M. Constantine, and Yoram Vodovotz 9 In Silico Trials and Personalized Therapy for Sepsis and Trauma .... 159 Yoram Vodovotz, John Bartels, and Gary An Part III Translational Modeling of Wound Healing 10 Disorder of Localized Infl ammation in Wound Healing: A Systems Perspective ........................................................................... 173 Sashwati Roy, Amitava Das, and Chandan K. Sen 11 Equation-Based Models of Wound Healing and Collective Cell Migration ........................................................................................ 185 Julia Arciero and David Swigon 12 Agent-Based Models of Wound Healing .............................................. 209 Jordan R. Stern, Cordelia Ziraldo, Yoram Vodovotz, and Gary An Part IV Translational Modeling of Host-Pathogen Interactions 13 Modeling Host–Pathogen Interactions in Necrotizing Enterocolitis ................................................................... 231 Julia Arciero, Jared Barber, and Moses Kim 14 Modeling Host–Vector–Pathogen Immuno- infl ammatory Interactions in Malaria .......................................................................... 265 Yoram Vodovotz, Nabil Azhar, Natasa Miskov-Zivanov, Marius Buliga, Ruben Zamora, Bard Ermentrout, Gregory M. Constantine, James R. Faeder, Nazzy Pakpour, and Shirley Luckhart Part V Future Perspectives: Translation to Implementation 15 The Rationale and Implementation of Translational Systems Biology as a New Paradigm for the Study of Infl ammation ....................................................................................... 283 Gary An and Yoram Vodovotz Index ................................................................................................................. 289 Contributors Gary An, M.D. Department of Surgery , University of Chicago , Chicago , IL , USA Ioannis P. Androulakis, Ph.D. Biomedical Engineering , Rutgers University , Piscataway , NJ , USA Julia Arciero, Ph.D. Department of Mathematical Sciences , Indiana University- Purdue University Indianapolis , Indianapolis , IN , USA Nabil Azhar, B.S. Department of Computational and Systems Biology , University of Pittsburgh , Pittsburgh , PA , USA Jared Barber, Ph.D. Department of Mathematical Sciences , University of Pittsburgh , Pittsburgh , PA , USA John Bartels, M.S. Immunetrics, Inc. , Pittsburgh , PA , USA Timothy R. Billiar, M.D. Department of Surgery , Presbyterian Hospital , Pittsburgh , PA , USA Marius Buliga, Ph.D. University of Pittsburgh at Bradford , Bradford , PA , USA Steve E. Calvano, Ph.D. Department of Surgery , UMDNJ-Robert Wood Johnson Medical School , New Brunswick , NJ , USA Scott Christley, Ph.D. Department of Surgery , University of Chicago , Chicago , IL , USA Gilles Clermont, M.D., M.Sc. Department of Critical Care Medicine , UPMC Presbyterian Hospital , Pittsburgh , PA , USA Gregory M. Constantine, Ph.D. Department of Mathematics , University of Pittsburgh , Pittsburgh , PA , USA Amitava Das, M. Pharm Comprehensive Wound Center, Department of Surgery, Davis Heart & Lung Research Institute , The Ohio State University Wexner Medical Center , Columbus , OH , USA ix x Contributors Rishi R. Dhingra, B.S. Department of Neurosciences , Case Western Reserve University , Cleveland , OH , USA Thomas E. Dick, Ph.D. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine , Case Western Reserve University , Cleveland , OH , USA Bard Ermentrout, Ph.D. Department of Mathematics , University of Pittsburgh , Pittsburgh , PA , USA James R. Faeder, Ph.D. Department of Computational and Systems Biology , University of Pittsburgh ,