Computational Modeling Of Genetic And Biochemical Networks

How new modeling techniques can be used to explore functionally relevant molecular and cellular relationships.

This book serves as an introduction to the myriad computational approaches to gene regulatory modeling and analysis, and is written specifically with experimental biologists in mind. Mathematical jargon is avoided and explanations are given in intuitive terms. In cases where equations are unavoidable, they are derived from first principles or, at the very least, an intuitive description is provided. Extensive examples and a large number of model descriptions are provided for use in both classroom exercises as well as self-guided exploration and learning. As such, the book is ideal for self-learning and also as the basis of a semester-long course for undergraduate and graduate students in molecular biology, bioengineering, genome sciences, or systems biology./a

This issue on Computational Models for Cell Processes is based on a workshop that took place in Turku, Finland, May 2008. The papers span a mix of approaches to systems biology, ranging from quantitative techniques to computing paradigms inspired by biology.

We propose a theoretical, yet realistic agent-based model and simulation platform of animal embryogenesis, called MecaGen, centered on the physico-chemical coupling of cell mechanics with gene expression and molecular signaling. This project aims to investigate the multiscale dynamics of the early stages of biological morphogenesis. Here, embryonic development is viewed as an emergent, self-organized phenomenon based on a myriad of cells and their genetically regulated, and regulating, biomechanical behavior. Cells’ mechanical properties (such as division rate, adhesion strength, or intrinsic motility) are closely correlated with their spatial location and temporal state of genetic and molecular dynamics (such as internal protein and external ligand concentrations) and affect each other concurrently. In a second part, we illustrate our model on artificial data (gene regulation motifs and cell sorting), then demonstrate a customization and application to a real biological case study in the zebrafish early development. We use as an example the episode of intercalation patterns appearing during the first phase of epiboly and the movements of the deep cells between the yolk and the enveloping layer. A domain of the model’s multidimensional parameter space is explored systematically, while experimental data obtained from microscopy imaging of live embryos is used to measure the “fitness” of the virtual embryo and validate our hypotheses.

This dissertation, "Construction and Computation Methods for Biological Networks" by Hao, Jiang, 姜昊, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Biological systems are complex in that they comprise large number of interacting entities, and their dynamics follow mechanic regulations for movement and biological function organization. Established computational modeling deals with studying and manipulating biologically relevant systems as a powerful approach. Inner structure and behavior of complex biological systems can be analyzed and understood by computable biological networks. In this thesis, models and computation methods are proposed for biological networks. The study of Genetic Regulatory Networks (GRNs) is an important research topic in genomic research. Several promising techniques have been proposed for capturing the behavior of gene regulations in biological systems. One of the promising models for GRNs, Boolean Network (BN) has gained a lot of attention. However, little light has been shed on the analysis of internal connection between the dynamics of biological molecules and network systems. Inference and completion problems of a BN from a given set of singleton attractors are considered to be important in understanding the relationship between dynamics of biological molecules and network systems. Discrete dynamic systems model has been recently proposed to model time-course microarray measurements of genes, but delay effect may be modeled as a realistic factor in studying GRNs. A delay discrete dynamic systems model is developed to model GRNs. Inference and analysis of networks is one of the grand challenges in modern statistical biology. Machine learning method, in particular, Support Vector Machine (SVM), has been successfully applied in predictions of internal connections embedded in networks. Kernels in conjunction with SVM demonstrate strong ability in performing various tasks such as biomedical diagnosis, function prediction and motif extractions. In biomedical diagnosis, data sets are always high dimensional which provide a challenging research problem in machine learning area. Novel kernels using distance-metric that are not common in machine learning framework are proposed for possible tumor differentiation discrimination problem. Protein function prediction problem is a hot topic in bioinformatics. The K-spectrum Kernel is among the top popular models in description of protein sequences. Taking into consideration of positive-semi-definiteness in kernel construction, Eigen-matrix translation technique is introduced in novel kernel formulation to give better prediction result. In a further step, power of Eigen-matrix translation technique in feature selection is demonstrated through mathematical formulation. Due to structure complexity of carbohydrates, the study of carbohydrate sugar chains has lagged behind compared to that of DNA and proteins. A weighted q-gram kernel is constructed in classifying glycan structures with limitations in feature extractions. A biochemically-weighted tree kernel is then proposed to enhance the ability in both classification as well as motif extractions. Finally the problem of metabolite biomarker discovery is researched. Human diseases, in particular metabolic diseases, can be directly caused by the lack of essential metabolites. Identification of metabolite biomarkers has significant importance in the study of biochemical reaction and signaling networks. A promising computational approach is proposed to identify metabolic biomarkers through integrating biomedical data an

The new research area of genomics-inspired network biology lacks an introductory book that enables both physical/computational scientists and biologists to obtain a general yet sufficiently rigorous perspective of current thinking. Filling this gap, Introduction to Biological Networks provides a thorough introduction to genomics-inspired network bi

This chapter describes the computational methods for estimating, modeling, and simulating biological systems. It also presents two approaches to understand biological systems and describes a method and a software tool developed by our research group. Bayesian network is a mathematical model for representing causal relationships among random variables by using conditional probabilities. The conditional probabilities describe the parent-child relationships and can be viewed as an extension of the deterministic models like Boolean networks. This model is suited for modeling qualitative relations between genes and allows mathematical and algorithmic analyses. We also devised a method to infer a gene network in terms of a linear system of differential equations from time-course gene expression data. A software tool is developed based on Petri net to modeling and simulation of gene networks. With this software tool, various models have been constructed and its utility has been demonstrated in practice.

The emerging, multi-disciplinary field of systems biology is devoted to the study of the relationships between various parts of a biological system, and computer modeling plays a vital role in the drive to understand the processes of life from an holistic viewpoint. Advancements in experimental technologies in biology and medicine have generated an enormous amount of biological data on the dependencies and interactions of many different molecular cell processes, fueling the development of numerous computational methods for exploring this data. The mathematical formalism of Petri net theory is able to encompass many of these techniques. This essential text/reference presents a comprehensive overview of cutting-edge research in applications of Petri nets in systems biology, with contributions from an international selection of experts. Those unfamiliar with the field are also provided with a general introduction to systems biology, the foundations of biochemistry, and the basics of Petri net theory. Further chapters address Petri net modeling techniques for building and analyzing biological models, as well as network prediction approaches, before reviewing the applications to networks of different biological classification. Topics and features: investigates the modular, qualitative modeling of regulatory networks using Petri nets, and examines an Hybrid Functional Petri net simulation case study; contains a glossary of the concepts and notation used in the book, in addition to exercises at the end of each chapter; covers the topological analysis of metabolic and regulatory networks, the analysis of models of signaling networks, and the prediction of network structure; provides a biological case study on the conversion of logical networks into Petri nets; discusses discrete modeling, stochastic modeling, fuzzy modeling, dynamic pathway modeling, genetic regulatory network modeling, and quantitative analysis techniques; includes a Foreword by Professor Jens Reich, Professor of Bioinformatics at Humboldt University and Max Delbrück Center for Molecular Medicine in Berlin. This unique guide to the modeling of biochemical systems using Petri net concepts will be of real utility to researchers and students of computational biology, systems biology, bioinformatics, computer science, and biochemistry.