Quantitative Assessment and Validation of Network Inference Methods in Bioinformatics


Book Description

Scientists today have access to an unprecedented arsenal of high-tech tools that can be used to thoroughly characterize biological systems of interest. High-throughput “omics” technologies enable to generate enormous quantities of data at the DNA, RNA, epigenetic and proteomic levels. One of the major challenges of the post-genomic era is to extract functional information by integrating such heterogeneous high-throughput genomic data. This is not a trivial task as we are increasingly coming to understand that it is not individual genes, but rather biological pathways and networks that drive an organism’s response to environmental factors and the development of its particular phenotype. In order to fully understand the way in which these networks interact (or fail to do so) in specific states (disease for instance), we must learn both, the structure of the underlying networks and the rules that govern their behavior. In recent years there has been an increasing interest in methods that aim to infer biological networks. These methods enable the opportunity for better understanding the interactions between genomic features and the overall structure and behavior of the underlying networks. So far, such network models have been mainly used to identify and validate new interactions between genes of interest. But ultimately, one could use these networks to predict large-scale effects of perturbations, such as treatment by multiple targeted drugs. However, currently, we are still at an early stage of comprehending methods and approaches providing a robust statistical framework to quantitatively assess the quality of network inference and its predictive potential. The scope of this Research Topic in Bioinformatics and Computational Biology aims at addressing these issues by investigating the various, complementary approaches to quantify the quality of network models. These “validation” techniques could focus on assessing quality of specific interactions, global and local structures, and predictive ability of network models. These methods could rely exclusively on in silico evaluation procedures or they could be coupled with novel experimental designs to generate the biological data necessary to properly validate inferred networks.




Quantitative Assessment and Validation of Network Inference Methods in Bioinformatics


Book Description

Scientists today have access to an unprecedented arsenal of high-tech tools that can be used to thoroughly characterize biological systems of interest. High-throughput "omics" technologies enable to generate enormous quantities of data at the DNA, RNA, epigenetic and proteomic levels. One of the major challenges of the post-genomic era is to extract functional information by integrating such heterogeneous high-throughput genomic data. This is not a trivial task as we are increasingly coming to understand that it is not individual genes, but rather biological pathways and networks that drive an organism's response to environmental factors and the development of its particular phenotype. In order to fully understand the way in which these networks interact (or fail to do so) in specific states (disease for instance), we must learn both, the structure of the underlying networks and the rules that govern their behavior. In recent years there has been an increasing interest in methods that aim to infer biological networks. These methods enable the opportunity for better understanding the interactions between genomic features and the overall structure and behavior of the underlying networks. So far, such network models have been mainly used to identify and validate new interactions between genes of interest. But ultimately, one could use these networks to predict large-scale effects of perturbations, such as treatment by multiple targeted drugs. However, currently, we are still at an early stage of comprehending methods and approaches providing a robust statistical framework to quantitatively assess the quality of network inference and its predictive potential. The scope of this Research Topic in Bioinformatics and Computational Biology aims at addressing these issues by investigating the various, complementary approaches to quantify the quality of network models. These "validation" techniques could focus on assessing quality of specific interactions, global and local structures, and predictive ability of network models. These methods could rely exclusively on in silico evaluation procedures or they could be coupled with novel experimental designs to generate the biological data necessary to properly validate inferred networks.




Gene Network Inference


Book Description

This book presents recent methods for Systems Genetics (SG) data analysis, applying them to a suite of simulated SG benchmark datasets. Each of the chapter authors received the same datasets to evaluate the performance of their method to better understand which algorithms are most useful for obtaining reliable models from SG datasets. The knowledge gained from this benchmarking study will ultimately allow these algorithms to be used with confidence for SG studies e.g. of complex human diseases or food crop improvement. The book is primarily intended for researchers with a background in the life sciences, not for computer scientists or statisticians.




Gene Quantification


Book Description

Geneticists and molecular biologists have been interested in quantifying genes and their products for many years and for various reasons (Bishop, 1974). Early molecular methods were based on molecular hybridization, and were devised shortly after Marmur and Doty (1961) first showed that denaturation of the double helix could be reversed - that the process of molecular reassociation was exquisitely sequence dependent. Gillespie and Spiegelman (1965) developed a way of using the method to titrate the number of copies of a probe within a target sequence in which the target sequence was fixed to a membrane support prior to hybridization with the probe - typically a RNA. Thus, this was a precursor to many of the methods still in use, and indeed under development, today. Early examples of the application of these methods included the measurement of the copy numbers in gene families such as the ribosomal genes and the immunoglo bulin family. Amplification of genes in tumors and in response to drug treatment was discovered by this method. In the same period, methods were invented for estimating gene num bers based on the kinetics of the reassociation process - the so-called Cot analysis. This method, which exploits the dependence of the rate of reassociation on the concentration of the two strands, revealed the presence of repeated sequences in the DNA of higher eukaryotes (Britten and Kohne, 1968). An adaptation to RNA, Rot analysis (Melli and Bishop, 1969), was used to measure the abundance of RNAs in a mixed population.




Proteomics Data Analysis


Book Description

This thorough book collects methods and strategies to analyze proteomics data. It is intended to describe how data obtained by gel-based or gel-free proteomics approaches can be inspected, organized, and interpreted to extrapolate biological information. Organized into four sections, the volume explores strategies to analyze proteomics data obtained by gel-based approaches, different data analysis approaches for gel-free proteomics experiments, bioinformatic tools for the interpretation of proteomics data to obtain biological significant information, as well as methods to integrate proteomics data with other omics datasets including genomics, transcriptomics, metabolomics, and other types of data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detailed implementation advice that will ensure high quality results in the lab. Authoritative and practical, Proteomics Data Analysis serves as an ideal guide to introduce researchers, both experienced and novice, to new tools and approaches for data analysis to encourage the further study of proteomics.




Encyclopedia of Bioinformatics and Computational Biology


Book Description

Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics, Three Volume Set combines elements of computer science, information technology, mathematics, statistics and biotechnology, providing the methodology and in silico solutions to mine biological data and processes. The book covers Theory, Topics and Applications, with a special focus on Integrative –omics and Systems Biology. The theoretical, methodological underpinnings of BCB, including phylogeny are covered, as are more current areas of focus, such as translational bioinformatics, cheminformatics, and environmental informatics. Finally, Applications provide guidance for commonly asked questions. This major reference work spans basic and cutting-edge methodologies authored by leaders in the field, providing an invaluable resource for students, scientists, professionals in research institutes, and a broad swath of researchers in biotechnology and the biomedical and pharmaceutical industries. Brings together information from computer science, information technology, mathematics, statistics and biotechnology Written and reviewed by leading experts in the field, providing a unique and authoritative resource Focuses on the main theoretical and methodological concepts before expanding on specific topics and applications Includes interactive images, multimedia tools and crosslinking to further resources and databases




Bayesian Inference for Gene Expression and Proteomics


Book Description

Expert overviews of Bayesian methodology, tools and software for multi-platform high-throughput experimentation.




Probabilistic Boolean Networks


Book Description

The first comprehensive treatment of probabilistic Boolean networks, unifying different strands of current research and addressing emerging issues.




Systems Genetics


Book Description

Whereas genetic studies have traditionally focused on explaining heritance of single traits and their phenotypes, recent technological advances have made it possible to comprehensively dissect the genetic architecture of complex traits and quantify how genes interact to shape phenotypes. This exciting new area has been termed systems genetics and is born out of a synthesis of multiple fields, integrating a range of approaches and exploiting our increased ability to obtain quantitative and detailed measurements on a broad spectrum of phenotypes. Gathering the contributions of leading scientists, both computational and experimental, this book shows how experimental perturbations can help us to understand the link between genotype and phenotype. A snapshot of current research activity and state-of-the-art approaches to systems genetics are provided, including work from model organisms such as Saccharomyces cerevisiae and Drosophila melanogaster, as well as from human studies.




Drosophila Eye Development


Book Description

1 Kevin Moses It is now 25 years since the study of the development of the compound eye in Drosophila really began with a classic paper (Ready et al. 1976). In 1864, August Weismann published a monograph on the development of Diptera and included some beautiful drawings of the developing imaginal discs (Weismann 1864). One of these is the first description of the third instar eye disc in which Weismann drew a vertical line separating a posterior domain that included a regular pattern of clustered cells from an anterior domain without such a pattern. Weismann suggested that these clusters were the precursors of the adult ommatidia and that the line marks the anterior edge of the eye. In his first suggestion he was absolutely correct - in his second he was wrong. The vertical line shown was not the anterior edge of the eye, but the anterior edge of a moving wave of patterning and cell type specification that 112 years later (1976) Ready, Hansen and Benzer would name the "morphogenetic furrow". While it is too late to hear from August Weismann, it is a particular pleasure to be able to include a chapter in this Volume from the first author of that 1976 paper: Don Ready! These past 25 years have seen an astonishing explosion in the study of the fly eye (see Fig.