Complex Systems And Computational Biology Approaches To Acute Inflammation

This second edition expands upon and updates the vital research covered in its predecessor, by presenting state-of-the-art multidisciplinary and systems-oriented approaches to complex diseases arising from and driven by the acute inflammatory response. The chapters in this volume provide an introduction to different types of computational modeling, and how these methods can be applied to specific inflammatory diseases, with a focus on providing readers a roadmap for integrating advanced mathematical and computational techniques with traditional experimental methods. In this second edition, we cover both well-established and emerging modeling methods, especially state-of-the-art machine learning approaches and the integration of data-driven and mechanistic modeling. This volume introduces the concept of Model-based Precision Medicine as an alternative approach to the current view of Precision Medicine, based on leveraging mechanistic computational modeling to decrease cost while increasing the information value of the data being obtained. By presenting the role of computational modeling as an integrated component of the research process, Complex Systems and Computational Biology Approaches to Acute Inflammation: A Framework for Model-based Precision Medicine offers a window into the recent past, the present, and the future of computationally-augmented biomedical research.

Are we satisfied with the rate of drug development? Are we happy with the drugs that come to market? Are we getting our money’s worth in spending for basic biomedical research? In Translational Systems Biology, Drs. Yoram Vodovotz and Gary An address these questions by providing a foundational description the barriers facing biomedical research today and the immediate future, and how these barriers could be overcome through the adoption of a robust and scalable approach that will form the underpinning of biomedical research for the future. By using a combination of essays providing the intellectual basis of the Translational Dilemma and reports of examples in the study of inflammation, the content of Translational Systems Biology will remain relevant as technology and knowledge advances bring broad translational applicability to other diseases. Translational systems biology is an integrated, multi-scale, evidence-based approach that combines laboratory, clinical and computational methods with an explicit goal of developing effective means of control of biological processes for improving human health and rapid clinical application. This comprehensive approach to date has been utilized for in silico studies of sepsis, trauma, hemorrhage, and traumatic brain injury, acute liver failure, wound healing, and inflammation. Provides an explicit, reasoned, and systematic approach to dealing with the challenges of translational science across disciplines Establishes the case for including computational modeling at all stages of biomedical research and healthcare delivery, from early pre-clinical studies to long-term care, by clearly delineating efficiency and costs saving important to business investment Guides readers on how to communicate across domains and disciplines, particularly between biologists and computational researchers, to effectively develop multi- and trans-disciplinary research teams

"Integrative Approaches to the Molecular Physiology of Inflammation" presents contributions from the many different fields and approaches to the physiology and the molecular origins of inflammation; particularly those that may be involved in the development and evolution of diseased phenotypes. We selected among the wide scope and multiple views used to probe into the molecular origins of complex inflammatory phenotypes. This book consists of an Introductory Editorial and 6 thematic chapters encompassing 24 articles: 17 original research contributions and 7 review articles (5 reviews, 1 systematic review, and 1 minireview). Both, the research papers and the reviews provide varied and insightful approaches to different facets of inflammation with approaches ranging from general inflammation and signaling depictions deeply rooted on functional biology and physiology, to computational systems biology analyses, translational medicine, and pharmacological explorations. Model systems are also quite diverse: human subjects, mice and other mammal models, cell cultures and in silico, complex networks and database studies.

Biomaterials have existed for millennia as mechanical replacement structures following disease or injury. Biomaterial design has changed markedly from structural support with an “inert immune profile as the primary objective to designs that elicit an integrative local tissue response and a pro-repair immune cell phenotype. Immunomodulatory Biomaterials: Regulating the Immune Response with Biomaterials to Affect Clinical Outcome offers a single, comprehensive reference on biomaterials for modulation of the host response, for materials scientists, tissue engineers and those working in regenerative medicine. This book details methods, materials and strategies designed to regulate the host immune response following surgical implantation and thus facilitate specific local cell infiltration and tissue deposition. There has been a dramatic transformation in our understanding of the role of the immune system, both innate and adaptive; these changes include recognition of the plasticity of immune cells, especially macrophages, cross-talk between the immune system and stem cells, and the necessity for in situ transition between inflammatory and regulatory immune cell phenotypes. The exploitation of these findings and the design and manufacture of new biomaterials is occurring at an astounding pace. There is currently no book directed at the interdisciplinary principles guiding the design, manufacture, testing, and clinical translation of biomaterials that proactively regulate the host tissue immune response. The challenge for academia, industry, and regulatory agencies to encourage innovation while assuring safety and maximizing efficacy has never been greater. Given the highly interdisciplinary requirements for the design, manufacture and use of immunomodulatory biomaterials, this book will prove a useful single resource across disciplines. Holistically covers the design, manufacture, testing, and clinical translation of biomaterials that proactively regulate the host tissue immune response Provides a single reference for understanding and utilizing the host response in biomaterials design An international collaboration of leading researchers in the field offering a novel insight into this fast-growing area

Development of powerful new high- throughput technologies for probing the transcriptome, proteome and metabolome is driving the rapid acquisition of information on the function of molecular systems. The importance of these achievements cannot be understated – they have transformed the nature of both biology and medicine. Despite this dramatic progress, one of the greatest challenges that continues to confront modern biology is to understand how behavior at the level of genome, proteome and metabolome determines physiological function at the level of cell, tissue and organ in both health and disease. Because of the inherent complexity of biological systems, the development, analysis, and validation of integrative computational models based directly on experimental data is necessary to achieve this understanding. This approach, known as systems biology, integrates computational and experimental approaches through iterative development of mathematical models and experimental validation and testing. The combination of these approaches allows for a mechanistic understanding of the function of complex biological systems in health and their dysfunction in disease. The National Heart, Lung, and Blood Institute (NHLBI) has recognized the importance of the systems biology approach for understanding normal physiology and perturbations associated with heart, lung, blood, and sleep diseases and disorders. In 2006, NHLBI announced the Exploratory Program in Systems Biology, followed in 2010 by the NHLBI Systems Biology Collaborations. The goal of these programs is to support collaborative teams of investigators in using experimental and computational strategies to integrate the component parts of biological networks and pathways into computational models that are based firmly on and validated using experimental data. These validated models are then applied to gain insights into the mechanisms of altered system function in disease, to generate novel hypotheses regarding these mechanisms that can be tested experimentally, and to then use the results of experiments to refine the models. The purpose of this Research Topic is to present the range of innovative, new approaches being developed by investigators working in areas of systems biology that couple experimental and modeling studies to understand the cause and possible treatment of heart, lung, blood and sleep diseases and disorders. This Research Topic will be of great interest to the cardiovascular research community as well as to the general community of systems biologists.

While systems biology and pharmacodynamics have evolved in parallel, there are significant interrelationships that can enhance drug discovery and enable optimized therapy for each patient. Systems pharmacology is the relatively new discipline that is the interface between these two methods. This book is the first to cover the expertise from systems biology and pharmacodynamics researchers, describing how systems pharmacology may be developed and refined further to show practical applications in drug development. There is a growing awareness that pharmaceutical companies should reduce the high attrition in the pipeline due to insufficient efficacy or toxicity found in proof-of-concept and/or Phase II studies. Systems Pharmacology and Pharmacodynamics discusses the framework for integrating information obtained from understanding physiological/pathological pathways (normal body function system vs. perturbed system due to disease) and pharmacological targets in order to predict clinical efficacy and adverse events through iterations between mathematical modeling and experimentation.