Mapping Genetic Interaction Networks in Yeast
Author | : Anastasija Baryshnikova |
Publisher | : |
Total Pages | : |
Release | : 2013 |
Genre | : |
ISBN | : |
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Author | : Anastasija Baryshnikova |
Publisher | : |
Total Pages | : |
Release | : 2013 |
Genre | : |
ISBN | : |
Author | : Amy Hin Yan Tong |
Publisher | : Library and Archives Canada = Bibliothèque et Archives Canada |
Total Pages | : 474 |
Release | : 2005 |
Genre | : |
ISBN | : 9780494028339 |
In chapter four, I describe the application of SGA analysis to the large-scale mapping of genetic interactions. A genetic interaction network containing & sim;1000 genes and & sim;4000 interactions was mapped by crossing mutations in 132 different query genes into a set of & sim;4700 viable gene deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity is predictive of function because interactions often occur among functionally related genes. Genetic interactions are largely orthogonal (non-overlapping) with protein-protein interactions, but genes coding for proteins that occur in the same pathway or complex display similar patterns of genetic interactions. The genetic network shows dense local neighbourhoods, implying the position of a gene on a partially mapped network is predictive of interactions. Because genetic networks are likely conserved, synthetic genetic interactions may underlie the complex genetics associated with inherited phenotypes in other organisms. In chapter three, I describe the development of a new method for automated identification of genetic interactions, termed synthetic genetic array (SGA) analysis. SGA analysis allows systematic construction of double mutants and examination of their fitness on a genome-wide scale. Functional genomics approaches have provided the opportunity for systematic examination of all genes in a genome, generating functional information such as gene expression profiles, protein expression and localization profiles, protein-protein interaction networks, and systematic characterization of mutants. Budding yeast has been the organism of choice for many of these pioneering studies because of its facile genetics. Large-scale studies have made significant contributions to our understanding of complex biological systems, and this trend is continuously fueled by new development of high-throughput technologies. In this thesis, I describe a general strategy to study protein-protein interaction modules (chapter two). A protein-protein interaction network was generated by focusing on yeast SH3 domains and combining data derived from phage-display ligand consensus sequences and large-scale two-hybrid physical interactions. This study produced a network that is depleted of most false positive interactions and enriched for biologically relevant interactions.
Author | : Gabriel Waksman |
Publisher | : Springer Science & Business Media |
Total Pages | : 325 |
Release | : 2006-12-22 |
Genre | : Medical |
ISBN | : 0387245324 |
Gabriel Waksman Institute of Structural Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, United Kingdom Address for correspondence: Professor Gabriel Waksman Institute of Structural Molecular Biology Birkbeck and University College London Malet Street London WC1E 7H United Kingdom Email: g. waksman@bbk. ac. uk and g. waksman@ucl. ac. uk Phone: (+44) (0) 207 631 6833 Fax: (+44) (0) 207 631 6833 URL: http://people. cryst. bbk. ac. uk/?ubcg54a Gabriel Waksman is Professor of Structural Molecular Biology at the Institute of Structural Molecular Biology at UCL/Birkbeck, of which he is also the director. Before joining the faculty of UCL and Birkbeck, he was the Roy and Diana Vagelos Professor of Biochemistry and Molecular Biophysics at the Washington University School of Medicine in St Louis (USA). The rapidly evolving ?eld of protein science has now come to realize the ubiquity and importance of protein–protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of hi- throughput proteomics to monitor protein–protein interactions at an organism level, we can now safely state that protein–protein interactions are the norm and not the exception.
Author | : Sourav Bandyopadhyay |
Publisher | : |
Total Pages | : 316 |
Release | : 2010 |
Genre | : |
ISBN | : 9781109737707 |
The goal of understanding complex biological systems and how they are perturbed to cause disease has long been a central focus of biology. The past decade has seen the creation and maturation of a number of new technologies designed to study biological pathways on a genome-wide scale. Rather than obtaining information about the function of one gene or protein at a time, such approaches can offer insight into the activity of every gene and protein in the cell all in the context of one experiment. One fundamental mode of gathering biological insight is through identifying which proteins in the cell interact physically, such as those which form protein complexes or biochemical pathways. Techniques such as yeast-two hybrid and co-immunoprecipitation followed by mass spectrometry allow the determination of a physical interaction map which details binding interactions between proteins on a large scale. Another fundamental mode of biological discovery is through assaying genetic interactions which arise when mutations in two genes produce a phenotype that is surprising in light of each mutation's individual effects. For example a synthetic lethal genetic interaction is indicated when deletions in two genes which are not essential for viability cause lethality when deleted together. Genetic interaction maps can be determined in high-throughput via SGA (Synthetic Genetic Array) technology. In Chapter 2 we derive and analyze a large physical protein interaction map centered on a set of human protein kinases and show how biological insight can be derived from such large-scale screens. In Chapter 3, we develop methods for the comparison of such physical protein interaction maps between species in order to identify proteins whose function is conserved throughout millions of years of evolution. In Chapter 4 we develop algorithms to integrate both physical and genetic interactions together for the purpose of biological pathway discovery. Moreover, our approaches create maps of genetic interactions that provide a picture of the global organization of pathways and complexes within the cell, which we apply to create a map of functional relationships among protein complexes involved in chromosomal biology. In Chapter 6, we apply this approach in two different yeast species and discover that while physical protein interactions are largely conserved across species, many genetic interactions are rewired which gives us valuable insight into pathway architecture. Finally in Chapter 7, we focus on the discovery of genetic interactions involved in the DNA damage response by assaying how different gene mutants respond to a drug which causes DNA damage and then demonstration how this elucidates pathways involved in this process.
Author | : Jason B. Wolf |
Publisher | : Oxford University Press, USA |
Total Pages | : 348 |
Release | : 2000 |
Genre | : Science |
ISBN | : 9780195128062 |
Over the last two decades, research into epistasis has seen explosive growth and has moved the focus of research in evolutionary genetics from a traditional additive approach. We now know the effects of genes are rarely independent, and to reach a fuller understanding of the process of evolution we need to look at gene interactions as well as gene-environment interactions. This book is an overview of non-additive evolutionary genetics, integrating all work to date on all levels of evolutionary investigation of the importance of epistasis in the evolutionary process in general. It includes a historical perspective on this emerging field, in-depth discussion of terminology, discussions of the effects of epistasis at several different levels of biological organization and combinations of theoretical and experimental approaches to analysis.
Author | : Robert C. Elston |
Publisher | : Humana Press |
Total Pages | : 564 |
Release | : 2012-02-04 |
Genre | : Science |
ISBN | : 9781617795541 |
Recent advances in genetics over the last quarter of a century, especially in molecular techniques, have dramatically reduced the cost of determining genetic markers and hence opened up a field of research that is increasingly helping to detect, prevent and/or cure many diseases that afflict humans. In Statistical Human Genetics: Methods and Protocols expert researchers in the field describe statistical methods and computer programs in the detail necessary to make them more easily accessible to the beginner analyzing data. Written in the highly successful Methods in Molecular BiologyTM series format, with examples of running the programs and interpreting the program outputs, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results from human genetic data collected in the laboratory. Thorough and as much as possible intuitive, Statistical Human Genetics: Methods and Protocols aids scientists in understanding the computer programs and analytical procedures they need to use.
Author | : Florian Markowetz |
Publisher | : Cambridge University Press |
Total Pages | : 287 |
Release | : 2015-07-02 |
Genre | : Science |
ISBN | : 131638098X |
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.
Author | : Matthias Dehmer |
Publisher | : John Wiley & Sons |
Total Pages | : 441 |
Release | : 2011-04-08 |
Genre | : Medical |
ISBN | : 3527638083 |
The book introduces to the reader a number of cutting edge statistical methods which can e used for the analysis of genomic, proteomic and metabolomic data sets. In particular in the field of systems biology, researchers are trying to analyze as many data as possible in a given biological system (such as a cell or an organ). The appropriate statistical evaluation of these large scale data is critical for the correct interpretation and different experimental approaches require different approaches for the statistical analysis of these data. This book is written by biostatisticians and mathematicians but aimed as a valuable guide for the experimental researcher as well computational biologists who often lack an appropriate background in statistical analysis.
Author | : David J. Balding |
Publisher | : John Wiley & Sons |
Total Pages | : 1828 |
Release | : 2019-07-09 |
Genre | : Science |
ISBN | : 1119429250 |
A timely update of a highly popular handbook on statistical genomics This new, two-volume edition of a classic text provides a thorough introduction to statistical genomics, a vital resource for advanced graduate students, early-career researchers and new entrants to the field. It introduces new and updated information on developments that have occurred since the 3rd edition. Widely regarded as the reference work in the field, it features new chapters focusing on statistical aspects of data generated by new sequencing technologies, including sequence-based functional assays. It expands on previous coverage of the many processes between genotype and phenotype, including gene expression and epigenetics, as well as metabolomics. It also examines population genetics and evolutionary models and inference, with new chapters on the multi-species coalescent, admixture and ancient DNA, as well as genetic association studies including causal analyses and variant interpretation. The Handbook of Statistical Genomics focuses on explaining the main ideas, analysis methods and algorithms, citing key recent and historic literature for further details and references. It also includes a glossary of terms, acronyms and abbreviations, and features extensive cross-referencing between chapters, tying the different areas together. With heavy use of up-to-date examples and references to web-based resources, this continues to be a must-have reference in a vital area of research. Provides much-needed, timely coverage of new developments in this expanding area of study Numerous, brand new chapters, for example covering bacterial genomics, microbiome and metagenomics Detailed coverage of application areas, with chapters on plant breeding, conservation and forensic genetics Extensive coverage of human genetic epidemiology, including ethical aspects Edited by one of the leading experts in the field along with rising stars as his co-editors Chapter authors are world-renowned experts in the field, and newly emerging leaders. The Handbook of Statistical Genomics is an excellent introductory text for advanced graduate students and early-career researchers involved in statistical genetics.
Author | : Brenda Andrews |
Publisher | : |
Total Pages | : 0 |
Release | : 2016 |
Genre | : Endomycetales |
ISBN | : 9781621820550 |
Over the past century, studies of the budding yeast Saccharomyces cerevisiae have helped to unravel principles of nearly every aspect of eukaryotic cell biology--from metabolism and molecular genetics to cell division and differentiation. Thanks to its short generation time, ease of genetic manipulation, and suitability for high-throughput studies, yeast remains the focus of research in a vast number of laboratories worldwide. This laboratory manual provides a comprehensive collection of experimental procedures that continue to make budding yeast an informative model. The contributors describe methods for culturing and genetically modifying yeast, strategies and tools (e.g., gene deletion collections) for functional analyses, approaches for characterizing cell structure and morphology, and techniques to probe the modifications and interactions of various cellular constituents (e.g., using one- and two-hybrid screens). Strategies for studying metabolomics, complex traits, and evolution in yeast are also covered, as are methods to isolate and investigate new strains of yeast from the wild. Several additional chapters are devoted to bioinformatics tools and resources for yeast biology (e.g., the Saccharomyces Genome Database). This manual is therefore an essential resource for all researchers, from graduate level upward, who use budding yeast to explore the intricate workings of cells.