Modeling Biomolecular Networks in Cells shows how the interaction between the molecular components of basic living organisms can be modelled mathematically and the models used to create artificial biological entities within cells. Such forward engineering is a difficult task but the nonlinear dynamical methods espoused in this book simplify the biology so that it can be successfully understood and the synthesis of simple biological oscillators and rhythm-generators made feasible. Such simple units can then be co-ordinated using intercellular signal biomolecules. The formation of such man-made multicellular networks with a view to the production of biosensors, logic gates, new forms of integrated circuitry based on "gene-chips" and even biological computers is an important step in the design of faster and more flexible "electronics". The book also provides theoretical frameworks and tools with which to analyze the nonlinear dynamical phenomena which arise from the connection of building units in a biomolecular network.
Alternative techniques and tools for analyzing biomolecular networks With the recent rapid advances in molecular biology, high-throughput experimental methods have resulted in enormous amounts of data that can be used to study biomolecular networks in living organisms. With this development has come recognition of the fact that a complicated living organism cannot be fully understood by merely analyzing individual components. Rather, it is the interactions of components or biomolecular networks that are ultimately responsible for an organism's form and function. This book addresses the important need for a new set of computational tools to reveal essential biological mechanisms from a systems biology approach. Readers will get comprehensive coverage of analyzing biomolecular networks in cellular systems based on available experimental data with an emphasis on the aspects of network, system, integration, and engineering. Each topic is treated in depth with specific biological problems and novel computational methods: GENE NETWORKS—Transcriptional regulation; reconstruction of gene regulatory networks; and inference of transcriptional regulatory networks PROTEIN INTERACTION NETWORKS—Prediction of protein-protein interactions; topological structure of biomolecular networks; alignment of biomolecular networks; and network-based prediction of protein function METABOLIC NETWORKS AND SIGNALING NETWORKS—Analysis, reconstruction, and applications of metabolic networks; modeling and inference of signaling networks; and other topics and new trends In addition to theoretical results and methods, many computational software tools are referenced and available from the authors' Web sites. Biomolecular Networks is an indispensable reference for researchers and graduate students in bioinformatics, computational biology, systems biology, computer science, and applied mathematics.
Mathematical models have become invaluable tools for understanding the intricate dynamic behavior of complex biochemical and biological systems. Among computational strategies, logical modeling has been recently gaining interest as an alternative approach to address network dynamics. Due to its advantages, including scalability and independence of kinetic parameters, the logical modeling framework is becoming increasingly popular to study the dynamics of highly interconnected systems, such as cell cycle progression, T cell differentiation and gene regulation. Novel tools and standards have been developed to increase the interoperability of logical models, which can now be employ to respond a variety of biological questions. This Research Topic brings together the most recent and cutting-edge approaches in the area of logical modeling including, among others, novel biological applications, software development and model analysis techniques.
Cellular automata make up a class of completely discrete dynamical systems, which have became a core subject in the sciences of complexity due to their conceptual simplicity, easiness of implementation for computer simulation, and their ability to exhibit a wide variety of amazingly complex behavior. The feature of simplicity behind complexity of cellular automata has attracted the researchers' attention from a wide range of divergent fields of study of science, which extend from the exact disciplines of mathematical physics up to the social ones, and beyond. Numerous complex systems containing many discrete elements with local interactions have been and are being conveniently modelled as cellular automata. In this book, the versatility of cellular automata as models for a wide diversity of complex systems is underlined through the study of a number of outstanding problems using these innovative techniques for modelling and simulation.
By providing expositions to modeling principles, theories, computational solutions, and open problems, this reference presents a full scope on relevant biological phenomena, modeling frameworks, technical challenges, and algorithms. Up-to-date developments of structures of biomolecules, systems biology, advanced models, and algorithms Sampling techniques for estimating evolutionary rates and generating molecular structures Accurate computation of probability landscape of stochastic networks, solving discrete chemical master equations End-of-chapter exercises
Biological systems are inherently stochastic and uncertain. Thus, research in bioinformatics, biomedical engineering and computational biology has to deal with a large amount of uncertainties. Fuzzy logic has shown to be a powerful tool in capturing different uncertainties in engineering systems. In recent years, fuzzy logic based modeling and analysis approaches are also becoming popular in analyzing biological data and modeling biological systems. Numerous research and application results have been reported that demonstrated the effectiveness of fuzzy logic in solving a wide range of biological problems found in bioinformatics, biomedical engineering, and computational biology. Contributed by leading experts world-wide, this edited book contains 16 chapters presenting representative research results on the application of fuzzy systems to genome sequence assembly, gene expression analysis, promoter analysis, cis-regulation logic analysis and synthesis, reconstruction of genetic and cellular networks, as well as biomedical problems, such as medical image processing, electrocardiogram data classification and anesthesia monitoring and control. This volume is a valuable reference for researchers, practitioners, as well as graduate students working in the field of bioinformatics, biomedical engineering and computational biology.
Modelling Methodology for Physiology and Medicine, Second Edition, offers a unique approach and an unprecedented range of coverage of the state-of-the-art, advanced modeling methodology that is widely applicable to physiology and medicine. The second edition, which is completely updated and expanded, opens with a clear and integrated treatment of advanced methodology for developing mathematical models of physiology and medical systems. Readers are then shown how to apply this methodology beneficially to real-world problems in physiology and medicine, such as circulation and respiration. The focus of Modelling Methodology for Physiology and Medicine, Second Edition, is the methodology that underpins good modeling practice. It builds upon the idea of an integrated methodology for the development and testing of mathematical models. It covers many specific areas of methodology in which important advances have taken place over recent years and illustrates the application of good methodological practice in key areas of physiology and medicine. It builds on work that the editors have carried out over the past 30 years, working in cooperation with leading practitioners in the field. Builds upon and enhances the reader's existing knowledge of modeling methodology and practice Editors are internationally renowned leaders in their respective fields Provides an understanding of modeling methodologies that can address real problems in physiology and medicine and achieve results that are beneficial either in advancing research or in providing solutions to clinical problems
This book presents the most recent mathematical approaches to the growing research area of networks, oscillations, and collective motions in the context of biological systems. Bringing together the results of multiple studies of different biological systems, this book sheds light on the relations among these research themes. Included in this book are the following topics: feedback systems with time delay and threshold of sensing (dead zone), robustness of biological networks from the point of view of dynamical systems, the hardware-oriented neuron modeling approach, a universal mechanism governing the entrainment limit under weak forcing, the robustness mechanism of open complex systems, situation-dependent switching of the cues primarily relied on by foraging ants, and group chase and escape. Research on different biological systems is presented together, not separated by specializations or by model systems. Therefore, the book provides diverse perspectives at the forefront of current mathematical research on biological systems, especially focused on networks, oscillations, and collective motions. This work is aimed at advanced undergraduate, graduate, and postdoctoral students, as well as scientists and engineers. It will also be of great use for professionals in industries and service sectors owing to the applicability of topics such as networks and synchronizations.
The two-volume set LNBI 11465 and LNBI 11466 constitutes the proceedings of the 7th International Work-Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2019, held in Granada, Spain, in May 2019. The total of 97 papers presented in the proceedings, was carefully reviewed and selected from 301 submissions. The papers are organized in topical sections as follows: Part I: High-throughput genomics: bioinformatics tools and medical applications; omics data acquisition, processing, and analysis; bioinformatics approaches for analyzing cancer sequencing data; next generation sequencing and sequence analysis; structural bioinformatics and function; telemedicine for smart homes and remote monitoring; clustering and analysis of biological sequences with optimization algorithms; and computational approaches for drug repurposing and personalized medicine. Part II: Bioinformatics for healthcare and diseases; computational genomics/proteomics; computational systems for modelling biological processes; biomedical engineering; biomedical image analysis; and biomedicine and e-health.
An introduction to the quantitative modeling of biological processes, presenting modeling approaches, methodology, practical algorithms, software tools, and examples of current research. The quantitative modeling of biological processes promises to expand biological research from a science of observation and discovery to one of rigorous prediction and quantitative analysis. The rapidly growing field of quantitative biology seeks to use biology's emerging technological and computational capabilities to model biological processes. This textbook offers an introduction to the theory, methods, and tools of quantitative biology. The book first introduces the foundations of biological modeling, focusing on some of the most widely used formalisms. It then presents essential methodology for model-guided analyses of biological data, covering such methods as network reconstruction, uncertainty quantification, and experimental design; practical algorithms and software packages for modeling biological systems; and specific examples of current quantitative biology research and related specialized methods. Most chapters offer problems, progressing from simple to complex, that test the reader's mastery of such key techniques as deterministic and stochastic simulations and data analysis. Many chapters include snippets of code that can be used to recreate analyses and generate figures related to the text. Examples are presented in the three popular computing languages: Matlab, R, and Python. A variety of online resources supplement the the text. The editors are long-time organizers of the Annual q-bio Summer School, which was founded in 2007. Through the school, the editors have helped to train more than 400 visiting students in Los Alamos, NM, Santa Fe, NM, San Diego, CA, Albuquerque, NM, and Fort Collins, CO. This book is inspired by the school's curricula, and most of the contributors have participated in the school as students, lecturers, or both. Contributors John H. Abel, Roberto Bertolusso, Daniela Besozzi, Michael L. Blinov, Clive G. Bowsher, Fiona A. Chandra, Paolo Cazzaniga, Bryan C. Daniels, Bernie J. Daigle, Jr., Maciej Dobrzynski, Jonathan P. Doye, Brian Drawert, Sean Fancer, Gareth W. Fearnley, Dirk Fey, Zachary Fox, Ramon Grima, Andreas Hellander, Stefan Hellander, David Hofmann, Damian Hernandez, William S. Hlavacek, Jianjun Huang, Tomasz Jetka, Dongya Jia, Mohit Kumar Jolly, Boris N. Kholodenko, Markek Kimmel, Michał Komorowski, Ganhui Lan, Heeseob Lee, Herbert Levine, Leslie M Loew, Jason G. Lomnitz, Ard A. Louis, Grant Lythe, Carmen Molina-París, Ion I. Moraru, Andrew Mugler, Brian Munsky, Joe Natale, Ilya Nemenman, Karol Nienałtowski, Marco S. Nobile, Maria Nowicka, Sarah Olson, Alan S. Perelson, Linda R. Petzold, Sreenivasan Ponnambalam, Arya Pourzanjani, Ruy M. Ribeiro, William Raymond, William Raymond, Herbert M. Sauro, Michael A. Savageau, Abhyudai Singh, James C. Schaff, Boris M. Slepchenko, Thomas R. Sokolowski, Petr Šulc, Andrea Tangherloni, Pieter Rein ten Wolde, Philipp Thomas, Karen Tkach Tuzman, Lev S. Tsimring, Dan Vasilescu, Margaritis Voliotis, Lisa Weber
Electrophysiological tools and biologic delivery systems generally rely on non-optimal methods for gaining access through cellular membranes. Electrophysiological techniques that provide intracellular access, such as patch clamping, result in membrane holes and cell death in a matter of hours, while the delivery of bioactive materials are hampered by low bioavailability following passage through the endosomal pathways. In each case, the lipid bilayer backbone of the cellular membrane presents a formidable barrier to intracellular access. As biological gatekeepers, cell membranes not only physically define everything from whole organisms to individual organelles, they also prevent unobstructed flow of molecules between the inner and outer regions of the membrane. This occurs since the hydrophobic lipid acyl tails form a narrow hydrophobic layer a few nanometers thick, which is highly unfavorable for the passage of most hydrophilic molecules. It is this region that is one of the greatest obstacles to the dream of biotechnology seamlessly and non-destructively integrating synthetic components with biological systems. This thesis contributes to the understanding of how to rationally design devices that interact specifically with this hydrophobic region. In turn, this work begins to establish design guidelines for creating non-destructive, membrane-penetrating bio-inorganic interfaces. The beginning chapters focus on the development of the "stealth" probe platform. In nature, there exist specialized transmembrane proteins capable of incorporating into lipid bilayers by replicating the lipid hydrophilic-hydrophobic-hydrophilic structure. The stealth probe design mimics this structure by creating 2-10nm hydrophobic bands on otherwise hydrophilic structures. However, since current lithographic methods do not possess the necessary resolution, a new fabrication technique using a combination of top-down fabrication with bottom-up self-assembly methods was developed. This approach uses an evaporated chrome-gold-chrome stack and focused ion beam (FIB) milling, where the exposed edge of the embedded gold layer can be specifically functionalized with a hydrophobic thiol-mediated self-assembled monolayer. Chapter 3 explores the propensity for insertion and specific interaction of the stealth probe hydrophobic band with the hydrophobic lipid bilayer core. In order to gain quantitative insight into the interaction behavior, atomic force microscopy was used in conjunction with a new, stacked lipid bilayer testing platform. By using stacks of 100's to 1000's of lipid bilayers, substrate-probe interaction artifacts can be removed while simultaneously allowing precise determination of probe location within a lipid bilayer. It was found that completely hydrophilic probes reside in the hydrophilic hydration region between bilayers, whereas hydrophobically functionalized stealth probes preferred to reside in the bilayer core. This behavior was found to be independent of hydrophobic functionalization, with butanethiol and dodecanethiol both displaying preferential localization. The subsequent chapters explore how the molecular structure of the hydrophobic band and the band thickness affect membrane-probe interface stability. The lipid stack platform provides an easy method of force-clamp testing, which enabled quantitative extrapolation of the unstressed interface strength. A series of tests with various length alkanethiols found that the crystallinity of the molecules in the hydrophobic band is the dominant factor influencing interfacial stability. Surprisingly, hydrophobicity was found to be a secondary factor, although necessary to drive spontaneous membrane integration. Molecular length was also found to play a role in determining the ultimate interfacial strength, with short chain molecules similar in length to amino acid side chains promoting the most stable interfaces. The thickness of the hydrophobic band was found to regulate the interface structure. Bands with thicknesses comparable to that of the host lipid bilayer core likely promote a fused interface geometry, similar in structure to that of transmembrane protein-lipid bilayer interfaces. Thicker bands began to transition to a 'T-junction' interface that is characterized by a lower interface stability. Interestingly, the behavior of 10nm bands were indistinguishable from completely hydrophobic probes, reinforcing the importance of nanoscale patterning for stable membrane integration. Chapter 6 builds on the results of the previous chapters by exploring how various stealth probe geometries influence adhesion behavior. In agreement with force clamp testing, short disordered monolayers displayed strong integration into the bilayer core, while crystalline monolayers displayed extremely weak integration. Preliminary adhesion testing results with human red blood cells demonstrate that the stealth probe geometry holds promise for in vitro and in vivo platforms, expanding the results of this work from simply a biophysical test system to a real world example. Finally, the behavior of two hydrophobic bands either commensurately spaced with the hydrophobic core spacing in the bilayer stack, or incommensurately spaced in order to force one band to reside in the hydrophilic hydration layer, is explored. It was found that the commensurately spaced bands display superior strength to single band tips, which is attributed to the necessity to simultaneously rupture both membrane-hydrophobic band interfaces. Conversely, the incommensurately spaced probes display a significant destabilization of the interface. This is thought to be due to the forced residence of one hydrophobic band in a hydrophilic hydration layer. This result is intriguing for biologic delivery systems, as the nuclear double membrane presents a unique barrier geometry, and a double band system may provide a facile means for penetration.
This book is the first to report on theoretical breakthroughs on control of complex dynamical systems developed by collaborative researchers in the two fields of dynamical systems theory and control theory. As well, its basic point of view is of three kinds of complexity: bifurcation phenomena subject to model uncertainty, complex behavior including periodic/quasi-periodic orbits as well as chaotic orbits, and network complexity emerging from dynamical interactions between subsystems. Analysis and Control of Complex Dynamical Systems offers a valuable resource for mathematicians, physicists, and biophysicists, as well as for researchers in nonlinear science and control engineering, allowing them to develop a better fundamental understanding of the analysis and control synthesis of such complex systems.
