Complex Systems and Computational Biology Approaches to Acute Inflammation

288 Pages·2013·5.54 MB·English

by  Yoram Vodovotz Ph.D.

Yoram Vodovotz · Gary An Editors
Complex Systems
and Computational
Biology Approaches
to Acute
Infl 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
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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
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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
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