Download or read book In silico Modeling Gene Expression Utilizing Genomic Activity and 3D Contact Information written by Jordan Hughey and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Large scale genetic studies for numerous traits have implicated genetic variants across the genome. This is well illustrated through the recent genome wide association study (GWAS) of 1.2 million individuals leading to the discovery of 406 loci associated with tobacco and alcohol use (1). Yet, there still lies a knowledge gap of the functional mechanisms and biological etiology behind the variant-phenotype associations found. With the advances in modern genomic technologies, datasets often gather a multitude of biological measures, including DNA genotypes, RNA expression and epigenetic information (2). Association studies using these integrative datasets will not only implicate associated genes, but also reveal underlying mechanisms for diseases (3). Here, we look to understand the mechanisms behind gene regulation that influence complex traits. This will be accomplished by evaluating current transcriptome wide association study (TWAS) methods and developing a new multi-omic TWAS framework. Transcriptome wide association studies (TWAS) are a popular approach to multi- omic integrative methods. To date, TWAS methods rely on statistical models to predict gene expression due to a lack of individual level expression data available. These predicted expression values are further correlated to the phenotype of interest to see which genes (and their expression) effect the trait. Mainstream TWAS methods use genetic variants that are within a 1Mb distance from the gene as predictors for the gene's expression. This heuristic definition of cis-regulatory region is often not optimal and fails to pinpoint the true set of eQTLs. Alternatively, we propose using chromatin conformation data and enhancer activity marks to select the genetic variants used for transcriptome prediction. This will use molecular and spatial knowledge to have a biologically informed method in selecting genetic variants for expression prediction model training. Furthermore, we apply our approach to a cross-tissue framework for gene expression prediction, as well as an ensemble approach to produce optimal models from either cross-tissue or single tissue measures based on gene context. We implemented this suite of frameworks to 13 human tissues in the Genotype-Tissue Expression project and compare our findings to previous methods. Our approach resulted in an average gain of 52% and 14% more significant imputed models and an average of 44% and 5% improvement in prediction accuracy when compared to two widely-used methods: PrediXcan and UTMOST, respectively. Finally, we apply our expression prediction models to the genome-wide association results of the largest smoking and drinking use cohort to highlight our methods advantages for analyzing complex traits. We present that the improved expression prediction accuracy from multi-omic integration leads to increased power to detect gene-trait associations. Ultimately, this dissertation highlights the use of integrative approaches for genomic association studies. This dissertation provides a foundation for future epigenetic integration for association studies, and emphasizes that multi-omic approaches will substantially improve our understanding of the mechanisms behind complex traits.
Download or read book Computational Methods for Analyzing and Modeling Gene Regulation and 3D Genome Organization written by Anastasiya Belyaeva and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Biological processes from differentiation to disease progression are governed by gene regulatory mechanisms. Currently large-scale omics and imaging data sets are being collected to characterize gene regulation at every level. Such data sets present new opportunities and challenges for extracting biological insights and elucidating the gene regulatory logic of cells. In this thesis, I present computational methods for the analysis and integration of various data types used for cell profiling. Specifically, I focus on analyzing and linking gene expression with the 3D organization of the genome. First, I describe methodologies for elucidating gene regulatory mechanisms by considering multiple data modalities. I design a computational framework for identifying colocalized and coregulated chromosome regions by integrating gene expression and epigenetic marks with 3D interactions using network analysis. Then, I provide a general framework for data integration using autoencoders and apply it for the integration and translation between gene expression and chromatin images of naive T-cells. Second, I describe methods for analyzing single modalities such as contact frequency data, which measures the spatial organization of the genome, and gene expression data. Given the important role of the 3D genome organization in gene regulation, I present a methodology for reconstructing the 3D diploid conformation of the genome from contact frequency data. Given the ubiquity of gene expression data and the recent advances in single-cell RNA-sequencing technologies as well as the need for causal modeling of gene regulatory mechanisms, I then describe an algorithm as well as a software tool, difference causal inference (DCI), for learning causal gene regulatory networks from gene expression data. DCI addresses the problem of directly learning differences between causal gene regulatory networks given gene expression data from two related conditions. Finally, I shift my focus from basic biology to drug discovery. Given the current COVID19 pandemic, I present a computational drug repurposing platform that enables the identification of FDA approved compounds for drug repurposing and investigation of potential causal drug mechanisms. This framework relies on identifying drugs that reverse the signature of the infection in the space learned by an autoencoder and then uses causal inference to identify putative drug mechanisms.
Download or read book Vetinformatics An insight for decoding livestock systems through in silico biology written by Jun-Mo Kim and published by Frontiers Media SA. This book was released on 2023-11-15 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Hi C Data Analysis written by Silvio Bicciato and published by Humana. This book was released on 2022-09-04 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume details a comprehensive set of methods and tools for Hi-C data processing, analysis, and interpretation. Chapters cover applications of Hi-C to address a variety of biological problems, with a specific focus on state-of-the-art computational procedures adopted for the data analysis. 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 tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Hi-C Data Analysis: Methods and Protocols aims to help computational and molecular biologists working in the field of chromatin 3D architecture and transcription regulation.
Download or read book Modeling the 3D Conformation of Genomes written by G. Tiana and published by CRC Press. This book was released on 2021-03-31 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a timely summary of physical modeling approaches applied to biological datasets that describe conformational properties of chromosomes in the cell nucleus. The coverage ranges from introductory chapters to modeling aspects related to polymer physics, and data-driven models for genomic domains, and predicting 3D genome structur
Download or read book Chemoinformatics and Bioinformatics in the Pharmaceutical Sciences written by Navneet Sharma and published by Academic Press. This book was released on 2021-05-21 with total page 514 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemoinformatics and Bioinformatics in the Pharmaceutical Sciences brings together two very important fields in pharmaceutical sciences that have been mostly seen as diverging from each other: chemoinformatics and bioinformatics. As developing drugs is an expensive and lengthy process, technology can improve the cost, efficiency and speed at which new drugs can be discovered and tested. This book presents some of the growing advancements of technology in the field of drug development and how the computational approaches explained here can reduce the financial and experimental burden of the drug discovery process. This book will be useful to pharmaceutical science researchers and students who need basic knowledge of computational techniques relevant to their projects. Bioscientists, bioinformaticians, computational scientists, and other stakeholders from industry and academia will also find this book helpful. - Provides practical information on how to choose and use appropriate computational tools - Presents the wide, intersecting fields of chemo-bio-informatics in an easily-accessible format - Explores the fundamentals of the emerging field of chemoinformatics and bioinformatics
Download or read book Genomic Regulatory Systems written by Eric H. Davidson and published by Elsevier. This book was released on 2001-01-24 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: The interaction between biology and evolution has been the subject of great interest in recent years. Because evolution is such a highly debated topic, a biologically oriented discussion will appeal not only to scientists and biologists but also to the interested lay person. This topic will always be a subject of controversy and therefore any breaking information regarding it is of great interest.The author is a recognized expert in the field of developmental biology and has been instrumental in elucidating the relationship between biology and evolution. The study of evolution is of interest to many different kinds of people and Genomic Regulatory Systems: In Development and Evolution is written at a level that is very easy to read and understand even for the nonscientist.* Contents Include* Regulatory Hardwiring: A Brief Overview of the Genomic Control Apparatus and Its Causal Role in Development and Evolution * Inside the Cis-Regulatory Module: Control Logic and How the Regulatory Environment Is Transduced into Spatial Patterns of Gene Expression* Regulation of Direct Cell-Type Specification in Early Development* The Secret of the Bilaterians: Abstract Regulatory Design in Building Adult Body Parts* Changes That Make New Forms: Gene Regulatory Systems and the Evolution of Body Plans
Download or read book Translational Systems Biology Concepts and Practice for the Future of Biomedical Research written by Yoram Vodovotz and published by Academic Press. This book was released on 2017-11-13 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: Are we satisfied with the rate of drug development? Are we happy with the drugs that come to market? Are we getting our money s worth in spending for basic biomedical research? In Translational Systems Biology, Drs. Yoram Vodovotz and Gary An address these questions by providing a foundational description the barriers facing biomedical research today and the immediate future, and how these barriers could be overcome through the adoption of a robust and scalable approach that will form the underpinning of biomedical research for the future. By using a combination of essays providing the intellectual basis of the Translational Dilemma and reports of examples in the study of inflammation, the content of Translational Systems Biology will remain relevant as technology and knowledge advances bring broad translational applicability to other diseases. Translational systems biology is an integrated, multi-scale, evidence-based approach that combines laboratory, clinical and computational methods with an explicit goal of developing effective means of control of biological processes for improving human health and rapid clinical application. This comprehensive approach to date has been utilized for in silico studies of sepsis, trauma, hemorrhage, and traumatic brain injury, acute liver failure, wound healing, and inflammation. Provides an explicit, reasoned, and systematic approach to dealing with the challenges of translational science across disciplines Establishes the case for including computational modeling at all stages of biomedical research and healthcare delivery, from early pre-clinical studies to long-term care, by clearly delineating efficiency and costs saving important to business investment Guides readers on how to communicate across domains and disciplines, particularly between biologists and computational researchers, to effectively develop multi- and trans-disciplinary research teams "
Download or read book Accelerating Genetic Gain for Key Traits Using Genome Wide Association Studies and Genomic Selection Promising Breeding Tools for Sustainable Agriculture written by Sundeep Kumar and published by Frontiers Media SA. This book was released on 2024-01-08 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Bayesian Inference for Gene Expression and Proteomics written by Kim-Anh Do and published by Cambridge University Press. This book was released on 2006-07-24 with total page 437 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expert overviews of Bayesian methodology, tools and software for multi-platform high-throughput experimentation.
Download or read book Computer Aided Pharmaceutics and Drug Delivery written by Vikas Anand Saharan and published by Springer Nature. This book was released on 2022-05-30 with total page 767 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book examines the role of computer-assisted techniques for discovering, designing, optimizing and manufacturing new, effective, and safe pharmaceutical formulations and drug delivery systems. The book discusses computational approaches, statistical modeling and molecular modeling for the development and safe delivery of drugs in humans. The application of concepts of QbD (Quality by Design), DoE (Design of Experiments), artificial intelligence and in silico pharmacokinetic assessment/simulation have been made a lot easier with the help of commercial software and expert systems. This title provides in-depth knowledge of such useful software with illustrations from the latest researches. The book also fills in the gap between pharmaceutics and molecular modeling at micro, meso and maro scale by covering topics such as advancements in computer-aided Drug Design (CADD), drug-polymer interactions in drug delivery systems, molecular modeling of nanoparticles and pharmaceutics/bioinformatics. This book provides abundant applications of computers in formulation designing and characterization are provided as examples, case studies and illustrations. Short reviews of software, databases and expert systems have also been added to culminate the interest of readers for novel applications in formulation development and drug delivery. Computer-aided pharmaceutics and drug delivery is an authoritative reference source for all the latest scholarly update on emerging developments in computed assisted techniques for drug designing and development. The book is ideally designed for pharmacists, medical practitioners, students and researchers.
Download or read book Animal Biotechnology written by Ashish S. Verma and published by Academic Press. This book was released on 2013-11-04 with total page 685 pages. Available in PDF, EPUB and Kindle. Book excerpt: Animal Biotechnology introduces applications of animal biotechnology and implications for human health and welfare. It begins with an introduction to animal cell cultures and genome sequencing analysis and provides readers with a review of available cell and molecular tools. Topics here include the use of transgenic animal models, tissue engineering, nanobiotechnology, and proteomics. The book then delivers in-depth examples of applications in human health and prospects for the future, including cytogenetics and molecular genetics, xenografts, and treatment of HIV and cancers. All this is complemented by a discussion of the ethical and safety considerations in the field.Animal biotechnology is a broad field encompassing the polarities of fundamental and applied research, including molecular modeling, gene manipulation, development of diagnostics and vaccines, and manipulation of tissue. Given the tools that are currently available and the translational potential for these studies, animal biotechnology has become one of the most essential subjects for those studying life sciences. - Highlights the latest biomedical applications of genetically modified and cloned animals with a focus on cancer and infectious diseases - Provides firsthand accounts of the use of biotechnology tools, including molecular markers, stem cells, and tissue engineering
Download or read book Data Mining for Genomics and Proteomics written by Darius M. Dziuda and published by John Wiley & Sons. This book was released on 2010-07-16 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: Data Mining for Genomics and Proteomics uses pragmatic examples and a complete case study to demonstrate step-by-step how biomedical studies can be used to maximize the chance of extracting new and useful biomedical knowledge from data. It is an excellent resource for students and professionals involved with gene or protein expression data in a variety of settings.
Download or read book Methods in Systems Biology written by Daniel Jameson and published by Academic Press. This book was released on 2011-09-26 with total page 775 pages. Available in PDF, EPUB and Kindle. Book excerpt: Systems biology is a term used to describe a number of trends in bioscience research and a movement that draws on those trends. This volume in the Methods in Enzymology series comprehensively covers the methods in systems biology. With an international board of authors, this volume is split into sections that cover subjects such as machines for systems biology, protein production and quantification for systems biology, and enzymatic assays in systems biology research. This volume in the Methods in Enzymology series comprehensively covers the methods in systems biology With an international board of authors, this volume is split into sections that cover subjects such as machines for systems biology, protein production and quantification for systems biology, and enzymatic assays in systems biology research
Download or read book Long Range Control of Gene Expression written by Veronica van Heyningen and published by Academic Press. This book was released on 2011-09-02 with total page 415 pages. Available in PDF, EPUB and Kindle. Book excerpt: Long-Range Control of Gene Expression covers the current progress in understanding the mechanisms for genomic control of gene expression, which has grown considerably in the last few years as insight into genome organization and chromatin regulation has advanced. Discusses the evolution of cis-regulatory sequences in drosophila Includes information on genomic imprinting and imprinting defects in humans Includes a chapter on epigenetic gene regulation in cancer
Download or read book DOE Genomics written by and published by . This book was released on 2005 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt:
