This book presents the foundations of key problems in computational molecular biology and bioinformatics. It focuses on computational and statistical principles applied to genomes, and introduces the mathematics and statistics that are crucial for understanding these applications. The book features a free download of the R software statistics package and the text provides great crossover material that is interesting and accessible to students in biology, mathematics, statistics and computer science. More than 100 illustrations and diagrams reinforce concepts and present key results from the primary literature. Exercises are given at the end of chapters.

This book is dedicated to the multiple aspects, that is, biological, physical and computational of DNA and RNA molecules. These molecules, central to vital processes, have been experimentally studied by molecular biologists for five decades since the discovery of the structure of DNA by Watson and Crick in 1953. Recent progresses (e.g. use of DNA chips, manipulations at the single molecule level, availability of huge genomic databases...) have revealed an imperious need for theoretical modelling. Further progresses will clearly not be possible without an integrated understanding of all DNA and RNA aspects and studies.

The book is intended to be a desktop reference for advanced graduate students or young researchers willing to acquire a broad interdisciplinary understanding of the multiple aspects of DNA and RNA. It is divided in three main sections:

The first section comprises an introduction to biochemistry and biology of nucleic acids. The structure and function of DNA are reviewed in R. Lavery's chapter. The next contribution, by V. Fritsch and E. Westhof, concentrates on the folding properties of RNA molecules. The cellular processes involving these molecules are reviewed by J. Kadonaga, with special emphasis on the regulation of transcription. These chapters does not require any preliminary knowledge in the field (except that of elementary biology and chemistry).

The second section covers the biophysics of DNA and RNA, starting with basics in polymer physics in the contribution by R. Khokhlov. A large space is then devoted to the presentation of recent experimental and theoretical progresses in the field of single molecule studies. T. Strick's contribution presents a detailed description of the various micro-manipulation techniques, and reviews recent experiments on the interactions between DNA and proteins (helicases, topoisomerases, ...). The theoretical modeling of single molecules is presented by J. Marko, with a special attention paid to the elastic and topological properties of DNA. Finally, advances in the understanding of electrophoresis, a technique of crucial importance in everyday molecular biology, are exposed in T. Duke's contribution.

The third section presents provides an overview of the main computational approaches to integrate, analyse and simulate molecular and genetic networks. First, J. van Helden introduces a series of statistical and computational methods allowing the identification of short nucleic fragments putatively involved in the regulation of gene expression from sets of promoter sequences controlling co-expressed genes. Next, the chapter by Samsonova et al. connects this issue of transcriptional regulation with that of the control of cell differentiation and pattern formation during embryonic development. Finally, H. de Jong and D. Thieffry review a series of mathematical approaches to model the dynamical behaviour of complex genetic regulatory networks. This contribution includes brief descriptions and references to successful applications of these approaches, including the work of B. Novak, on the dynamical modelling of cell cycle in different model organisms, from yeast to mammals.

. Provides a comprehensive overview of the structure and function of DNA and RNA at the interface between physics, biology and information science.

This timely volume explores the use of CRISPR-Cas9 for genome editing, presenting cutting-edge techniques and their applications in treatment of disease. The chapters describe latest methods such as use of targetable nucleases, investigation of the non-coding genome, mouse genome editing, increasing of knock-in efficiency in mouse zygotes, and generation of reporter stem cells; the text contextualizes these methods in treatment of cardiovascular disease, diabetes mellitus, retinitis pigmentosa, and others. The final chapters round out the book with a discussion of controversies and future directions. Genome Editing is an essential, of-the-moment contribution to this rapidly growing field. Drawing from a wealth of international perspectives, it presents novel techniques and applications for the engineering of the human genome. This book is essential reading for all clinicians and researchers in stem cells, regenerative medicine, genomics, biochemical and biomedical engineering- especially those interested in learning more about genome editing and applying it in a targeted, specific way.

Mitochondrial DNA is one of the most closely explored genetic systems, because it can tell us so much about the human past. This book takes a unique perspective, presenting the disparate strands that must be tied together to exploit this system. From molecular biology to anthropology, statistics to ancient DNA, this first volume of three presents a comprehensive global picture and a critical appraisal of human mitochondrial DNA variation.

DNA Repair and Replication contains an up-to-date review of general principles of DNA replication and an overview of the multiple pathways involved in DNA repair. Specific DNA repair pathways, including base-excision repair, light-dependent direct reversal of UV-damage, nucleotide-excision repair, transcription-coupled repair, double-strand break repair, and mismatch repair, are each discussed in separate chapters.
Selected Contents:
-Base Excision Repair
-Eukaryotic DNA Mismatch Repair
-Double Strand Break Repair
-Functions of DNA Polymerases
-Somatic Hypermutation: A Mutational Panacea

This book reflects more than three decades of research on Cellular Automata (CA), and nearly a decade of work on the application of CA to model biological strings, which forms the foundation of 'A New Kind of Computational Biology' pioneered by the start-up, CARLBio. After a brief introduction on Cellular Automata (CA) theory and functional biology, it reports on the modeling of basic biological strings with CA, starting with the basic nucleotides leading to codon and anti-codon CA models. It derives a more involved CA model of DNA, RNA, the entire translation process for amino acid formation and the evolution of protein to its unique structure and function. In subsequent chapters the interaction of Proteins with other bio-molecules is also modeled. The only prior knowledge assumed necessary is an undergraduate knowledge of computer programming and biology. The book adopts a hands-on, "do-it-yourself" approach to enable readers to apply the method provided to derive the CA rules and comprehend how these are related to the physical 'rules' observed in biology. In a single framework, the authors have presented two branches of science - Computation and Biology. Instead of rigorous molecular dynamics modeling, which the authors describe as a Bottoms-Up model, or relying on the Top-Down new age Artificial Intelligence (AI) and Machine Language (ML) that depends on extensive availability of quality data, this book takes the best from both the Top-Down and Bottoms-up approaches and establishes how the behavior of complex molecules is represented in CA. The CA rules are derived from the basic knowledge of molecular interaction and construction observed in biological world but mapped to a few subset of known results to derive and predict results. This book is useful for students, researchers and industry practitioners who want to explore modeling and simulation of the physical world complex systems from a different perspective. It raises the inevitable the question - 'Are life and the universe nothing but a collection of continuous systems processing information'.

The birth and the development of molecular biology and, subsequently, of genetic engineering and biotechnology cannot be separated from the advancements in our knowledge of the genetics, biochemistry and physiology of bacteria and bacter- phages. Also most of the tools employed nowadays by biotechnologists are of bacterial (or bacteriophage) origin and the playground for most of the DNA manipulations still remains within bacteria. The relative simplicity of the bacterial cell, the short gene- tion times, the well defined and inexpensive culturing conditions which characterize bacteria and the auto-catalytic process whereby a wealth of in-depth information has been accumulated throughout the years have significantly contributed to generate a large number of knowledge-based, reliable and exploitable biological systems. The subtle relationships between phages and their hosts have produced a large amount of information and allowed the identification and characterization of a number of components which play essential roles in fundamental biological p- cesses such as DNA duplication, recombination, transcription and translation. For instance, to remain within the topic of this book, two important players in the or- nization of the nucleoid, FIS and IHF, have been discovered in this way. Indeed, it is difficult to find a single fundamental biological process whose structural and functional aspects are better known than in bacteria.

This volume presents a valuable and readily reproducible collection of established and emerging techniques on modern genetic analyses. Chapters focus on statistical or data mining analyses, genetic architecture, the burden of multiple testing, genetic variance, measuring epistasis, multifactor dimensionality reduction, and ReliefF. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Epistasis: Methods and Protocols aids scientists in continuing to study elucidate epistasis in the context of modern data availability.

Transcription factors are the molecules that the cell uses to interpret the genome: they possess sequence-specific DNA-binding activity, and either directly or indirectly influence the transcription of genes. In aggregate, transcription factors control gene expression and genome organization, and play a pivotal role in many aspects of physiology and evolution.

This book provides a reference for major aspects of transcription factor function, encompassing a general catalogue of known transcription factor classes, origins and evolution of specific transcription factor types, methods for studying transcription factor binding sites in vitro, in vivo, and in silico, and mechanisms of interaction with chromatin and RNA polymerase."

This book explores the current status of proteomics, an exciting new discipline, which is less than 10 years old. This new field has rapidly grown into a major commercial and research enterprise with great prospects for dramatically advancing our knowledge of basic biological and disease processes. The contributors to this book are an international panel of proteomics experts, who review and discuss the current status of specific technologies and approaches.
Proteomics represents an exciting new way to pursue biological and biomedical science at an unprecedented pace. Proteomics takes a broad, comprehensive, systematic approach to understanding biology that is generally unbiased and not dependent upon existing knowledge. The major components of proteomics from basic discovery using a range of alternative analytical methods to discovery validation and use for clinical applications are discussed. State-of-the-art protein profiling methods include high resolution two-dimensional gels, two-dimensional differential in-gel electrophoresis, LC-MS and LC-MS/MS using accurate mass tags, and protein identifications of proteins from gels using mass spectrometry methods are discussed in depth. Other chapters describe comprehensive characterization of proteomes using electrophoretic prefractionation and analyses of sub-proteomes based on specific posttranslational modifications including the phospho-proteome, the glyco-proteome, and nitrated proteins. These conventional proteome analysis chapters are complemented by discussion of emerging technologies and approaches such as affinity based biosensor proteomics as well as the use of protein microarrays, microfluidics and nanotechnology. Strategies for improving throughput by automation are also discussed. Additional chapters address the application of current proteome techniques to clinical problems and the availability of protein expression library resources for proteome studies.
. Authored by international experts in the field
. Covers a wide range of topics including 2-D gels, global proteomics using accurate mass tags, global proteomics using electrophoretic prefractionation, microfluidics, and nanotechnology
. Includes state-of-the-art protein profiling methods, and emerging technologies"

Significant advancements have been made in the study of chromatin structure and function over the past fifty years but none as spectacular as those made in the last decade due to the development of novel techniques and the ability to sequence large stretches of DNA. In Chromatin Protocols, Second Edition, expert researchers delineate these cutting-edge techniques via step-by-step laboratory methods and protocols, which encompass a wide array of topics from the isolation of nucleosomes, assembly of nucleosomes and study of the basic chromatin structure to detailed analysis of histone modifications and chromatin function. Written in the highly successful Methods in Molecular Biology (TM) series style, chapters include brief introductions to the subjects, lists of the necessary materials and reagents, readily reproducible protocols, and Notes sections which highlight tips on troubleshooting and avoiding known pitfalls. Comprehensive and up-to-date, Chromatin Protocols, Second Edition is a valuable tool for scientists studying various aspects of chromatin function and an ideal guide to aid in the development of new techniques as well as new ideas in the field of chromatin biology.

Structural Genomics and Drug Discovery: Methods and Protocols focuses on high throughput structure determination methods and how they can be applied to lay the groundwork for structure aided drug discovery. The methods and protocols that are described can be applied in any laboratory interested in using detailed structural information to advance the initial stages of drug discovery. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Structural Genomics and Drug Discovery: Methods and Protocols seeks to aid scientists in the further study into structural genomics approach as an efficient initial step toward drug discovery and the methods described will be useful to anyone interested in moving in this direction.

This book contains articles written by experts on a wide range of topics that are associated with the analysis and management of biological information at the molecular level. It contains chapters on RNA and protein structure analysis, DNA computing, sequence mapping, genome comparison, gene expression data mining, metabolic network modeling, and phyloinformatics. The important work of some representative researchers in bioinformatics is brought together for the first time in one volume. The topic is treated in depth and is related to, where applicable, other emerging technologies such as data mining and visualization. The goal of the book is to introduce readers to the principle techniques of bioinformatics in the hope that they will build on them to make new discoveries of their own. Contents: Exploring RNA Intermediate Conformations with the Massively Parallel Genetic Algorithm; Introduction to Self-Assembling DNA Nanostructures for Computation and Nanofabrication; Mapping Sequence to Rice FPC; Graph Theoretic Sequence Clustering Algorithms and their Applications to Genome Comparison; The Protein Information Resource for Functional Genomics and Proteomics; High-Grade Ore for Data Mining in 3D Structures; Protein Classification: A Geometric Hashing Approach; Interrelated Clustering: An Approach for Gene Expression Data Analysis; Creating Metabolic Network Models Using Text Mining and Expert Knowledge; Phyloinformatics and Tree Networks. Readership: Molecular biologists who rely on computers and mathematical scientists with interests in biology.

Eukaryotic DNA Damage Surveillance and Repair contains chapters from experts in the field of DNA damage detection, repair, and cell cycle control. The work reviews current understanding of how different types of DNA damage are detected and focuses on how these surveillance mechanisms are coupled to processes of DNA repair, cell cycle control, and apoptosis.
The title will be of interest to undergraduate/postgraduate students and academics alike.

Bioinformatics is a new and fast expanding area of biology encompassing the organization, analysis and interpretation of the huge amount of data emerging from sequencing and genome projects. Major new programs, software and internet facilities have evolved recently that enable bioinformatic analysis at the whole genome level and more novel technologies are currently being developed. Written by experts in the field, this concise yet informative volume covers all aspects of bioinformatics pertaining to genomic studies. It is an essential book for anyone involved in genomic science or bioinformatics.

This series encompasses design, synthesis, application, and analytical methods (including clinical and in vitro) for the study of these critical interactions. As our understanding of the genome and proteome expands, general developments in the field of DNA sequence specific interaction are likely to play an increasingly important role. Accordingly, manuscripts have been solicited from experts covering a diverse range of fields, reflecting the cross-disciplinary and dynamic nature of the series.

Volume 4 describes work on the modification of DNA by AT specific anticancer drugs, DNA alkylation events which involve metabolite generation, DNA sequence recognition by two selective binders, bulged DNA microenvironments as molecular targets, DNA sequence specific binding by short peptides and the analysis of DNA-protein interactions using DNase I footprinting methodology.

Features include:
Expert contributors from the Biomedical world
Emerging areas of drug design and therapeutic applications
Nucleic acid-protein interactions
Color graphics of molecular modeling analyses
New and emerging methodologies
"

This volume provides an overview of the methods currently employed for next-generation sequencing (NGS) data analysis, highlights their problems and limitations, demonstrates the applications and indicates the developing trends in various fields of genome research.

After genomic sequencing, microarray technology has emerged as a widely used platform for genomic studies in the life sciences. Microarray technology provides a systematic way to survey DNA and RNA variation. With the abundance of data produced from microarray studies, however, the ultimate impact of the studies on biology will depend heavily on data mining and statistical analysis. The contribution of this book is to provide readers with an integrated presentation of various topics on analyzing microarray data.

Fungal comparative genomics started in 2000 by the genome sequencing of several yeast species. Since then, over 30 fungal genome sequences have become available. This set represents a huge evolutionary divergence, but also contains closely related genomes. This volume describes how to use this set of genomes to trace events in genome evolution, to extract information about highly conserved and less conserved sequence elements, and to develop novel methods in genomics.

This book facilitates the introduction of SAGE into the laboratory and provides a framework for interpreting and comparing data derived from SAGE experiments. SAGE studies encompass 50,000 tags and can provide detailed knowledge of the 2000 most highly expressed genes in the tissue sample. The SAGE protocols presented are detailed, fully annotated, and tested, and are all written by experienced SAGE researchers from around the world.

Eminent scientists have contributed comprehensive reviews on all aspects of the genomics of Rhodococcus, Mycobacteria, Streptomyces and other organisms. The authors provide an insight into the many facets of large scale functional investigation in a variety of bacteria with the explicit goal to find common rules in the dynamic and structural organization of these organisms. This volume is the definitive guide to current research in this increasingly important area and is essential reading for all microbiologists, biotechnologists, and genome scientists.

As the emerging field of proteomics continues to expand at an extremely rapid rate, the relative quantification of proteins, targeted by their function, becomes its greatest challenge. Complex analytical strategies have been designed that allow comparative analysis of large proteomes, as well as in depth detection of the core proteome or the interaction network of a given protein of interest. In Functional Proteomics: Methods and Protocols, expert researchers describe the latest protocols being developed to address the problems encountered in high-throughput proteomics projects, with emphasis on the factors governing the technical choices for given applications. The case studies within the volume focus on the following three crucial aspects of the experimental design: 1) the strategy used for the selection, purification and preparation of the sample to be analyzed by mass spectrometry, 2) the type of mass spectrometer used and the type of data to be obtained from it, and 3) the method used for the interpretation of the mass spectrometry data and the search engine used for the identification of the proteins in the different types of sequence data banks available. As a part of the highly successful Methods in Molecular Biology (TM) series, the chapters compile step-by-step, readily reproducible laboratory protocols, lists of the necessary materials and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Functional Proteomics: Methods and Protocols is an ideal resource for all scientists pursuing this developing field and its multitudinous data.

Directed evolution comprises two distinct steps that are typically applied in an iterative fashion: (1) generating molecular diversity and (2) finding among the ensemble of mutant sequences those proteins that perform the desired fu- tion according to the specified criteria. In many ways, the second step is the most challenging. No matter how cleverly designed or diverse the starting library, without an effective screening strategy the ability to isolate useful clones is severely diminished. The best screens are (1) high throughput, to increase the likelihood that useful clones will be found; (2) sufficiently sen- tive (i. e. , good signal to noise) to allow the isolation of lower activity clones early in evolution; (3) sufficiently reproducible to allow one to find small improvements; (4) robust, which means that the signal afforded by active clones is not dependent on difficult-to-control environmental variables; and, most importantly, (5) sensitive to the desired function. Regarding this last point, almost anyone who has attempted a directed evolution experiment has learned firsthand the truth of the dictum "you get what you screen for. " The protocols in Directed Enzyme Evolution describe a series of detailed p- cedures of proven utility for directed evolution purposes. The volume begins with several selection strategies for enzyme evolution and continues with assay methods that can be used to screen enzyme libraries. Genetic selections offer the advantage that functional proteins can be isolated from very large libraries s- ply by growing a population of cells under selective conditions.

Genomics is a new and fast expanding area of biology encompassing high throughput or large scale experimentation at the whole genome level, and the organization, analysis and interpretation of the huge amount of data emerging from genome projects. Major new technologies have evolved recently that enable experimentation at the whole genome level, and more novel technologies are currently being developed. This volume describes in detail the new technology necessary to study the entire genome in a holistic manner and all the high throughput and large-scale experimental methodologies currently being used in genomic science. In addition the authors describe the progress of the newest technologies that are currently being developed. Written by experts in the field, this concise yet informative volume covers all aspects of technology pertaining to genomic studies. It is an essential book for anyone involved in genomic science.

Plasmids are fascinating entities which can replicate autonomously in bacterial, archaeal, and eukaryotic cells. They profit from the cellular environment of the host but can also carry a rich diversity of genes which can be beneficial for the host. Plasmids confer the ability to degrade organic compounds and to fix nitrogen. In addition, plasmids carry antibiotic resistance genes and their spread in pathogenic bacteria is of great medical importance. Plasmids are used in molecular studies of various organisms with ramifications in synthetic biology, medicine, ecology, and evolution, as well as basic research in molecular and structural biology. Written by acknowledged experts in the field, this volume provides an up-to-date treatment of the structure, function, and application of plasmids, with a particular emphasis on current and future trends. The book is aimed primarily at research scientists, graduate students, and professional scientists, but will also be of great interest to all