Systems Biology And Regulatory Genomics

This book constitutes the thoroughly refereed post-proceedings of two joint RECOMB 2005 satellite events: the First Annual Workshop on Systems Biology, RSB 2005 and the Second Annual Workshop on Regulatory Genomics, RRG 2005, held in San Diego, CA, USA in December 2005. It contains 21 revised full papers that address a broad variety of topics in systems biology and regulatory genomics.

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Practical Systems Biology provides a detailed overview of the different approaches used in this relatively new discipline, integrating bioinformatics, genomics, proteomics and metabolomics. Various areas of research are also discussed, including the use of computational models of biological processes, and post-genomic research.

The advent of genome sequencing and associated technologies has transformed biologists' ability to measure important classes of molecules and their interactions. This expanded cellular view has opened the field to thousands of interactions that previously were outside the researchers' reach. The processing and interpretation of these new vast quantities of interconnected data call for sophisticated mathematical models and computational methods. Systems biology meets this need by combining genomic knowledge with theoretical, experimental and computational approaches from a number of traditional scientific disciplines to create a mechanistic explanation of cellular systems and processes.Systems Biology I: Genomics and Systems Biology II: Networks, Models, and Applications offer a much-needed study of genomic principles and their associated networks and models. Written for a wide audience, each volume presents a timely compendium of essential information that is necessary for a comprehensive study of the subject. The chapters in the two volumes reflect the hierarchical nature of systems biology. Chapter authors-world-recognized experts in their fields-provide authoritative discussions on a wide range of topics along this hierarchy. Volume I explores issues pertaining to genomics that range from prebiotic chemistry to noncoding RNAs. Volume II covers an equally wide spectrum, from mass spectrometry to embryonic stem cells. The two volumes are meant to provide a reliable reference for students and researchers alike.

Transcription regulation is a complex process that can be considered and investigated from different perspectives. Traditionally and due to technical reasons (including the evolution of our understanding of the underlying processes) the main focus of the research was made on the regulation of expression through transcription factors (TFs), the proteins directly binding to DNA. On the other hand, intensive research is going on in the field of chromatin structure, remodeling and its involvement in the regulation. Whatever direction we select, we can speak about several levels of regulation. For instance, concentrating on TFs, we should consider multiple regulatory layers, starting with signaling pathways and ending up with the TF binding sites in the promoters and other regulatory regions. However, it is obvious that the TF regulation, also including the upstream processes, represents a modest portion of all processes leading to gene expression. For more comprehensive description of the gene regulation, we need a systematic and holistic view, which brings us to the importance of systems biology approaches. Advances in methodology, especially in high-throughput methods, result in an ever-growing mass of data, which in many cases is still waiting for appropriate consideration. Moreover, the accumulation of data is going faster than the development of algorithms for their systematic evaluation. Data and methods integration is indispensable for the acquiring a systematic as well as a systemic view. In addition to the huge amount of molecular or genetic components of a biological system, the even larger number of their interactions constitutes the enormous complexity of processes occurring in a living cell (organ, organism). In systems biology, these interactions are represented by networks. Transcriptional or, more generally, gene regulatory networks are being generated from experimental ChIPseq data, by reverse engineering from transcriptomics data, or from computational predictions of transcription factor (TF) – target gene relations. While transcriptional networks are now available for many biological systems, mathematical models to simulate their dynamic behavior have been successfully developed for metabolic and, to some extent, for signaling networks, but relatively rarely for gene regulatory networks. Systems biology approaches provide new perspectives that raise new questions. Some of them address methodological problems, others arise from the newly obtained understanding of the data. These open questions and problems are also a subject of this Research Topic.

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.

Comprehensive coverage of the many different aspects of systems biology, resulting in an excellent overview of the experimental and computational approaches currently in use to study biological systems. Each chapter represents a valuable introduction to one specific branch of systems biology, while also including the current state of the art and pointers to future directions. Following different methods for the integrative analysis of omics data, the book goes on to describe techniques that allow for the direct quantification of carbon fluxes in large metabolic networks, including the use of 13C labelled substrates and genome-scale metabolic models. The latter is explained on the basis of the model organism Escherichia coli as well as the human metabolism. Subsequently, the authors deal with the application of such techniques to human health and cell factory engineering, with a focus on recent progress in building genome-scale models and regulatory networks. They highlight the importance of such information for specific biological processes, including the ageing of cells, the immune system and organogenesis. The book concludes with a summary of recent advances in genome editing, which have allowed for precise genetic modifications, even with the dynamic control of gene expression. This is part of the Advances Biotechnology series, covering all pertinent aspects of the field with each volume prepared by eminent scientists who are experts on the topic in question.

The genomic revolution has opened up systematic investigations and engineering designs for various life forms. Systems biology and synthetic biology are emerging as two complementary approaches, which embody the breakthrough in biology and invite application of engineering principles. Systems Biology and Synthetic Biology emphasizes the similarity between biology and engineering at the system level, which is important for applying systems and engineering theories to biology problems. This book demonstrates to students, researchers, and industry that systems biology relies on synthetic biology technologies to study biological systems, while synthetic biology depends on knowledge obtained from systems biology approaches.