Designing Toxicogenomics to Support Decision Making in Environmental Toxicology

Designing Toxicogenomics to Support Decision Making in Environmental Toxicology
Author: Jessica Ewald
Publisher:
Total Pages: 0
Release: 2022
Genre:
ISBN:

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"Traditional toxicity testing methods rely on exposing whole organisms to chemicals and observing high-level responses such as mortality and reproduction. These methods are too slow, expensive, and ethically concerning to assess the tens of thousands of legacy and novel substances in need of testing, and do not provide much biological insight into the toxicity mechanism. There has been a growing push to develop new approach methods for toxicity testing that do not use animal exposures. One major objective of this movement is to conduct exposures in vitro, measure comprehensive molecular outcomes, and use the molecular data to predict and manage risk to whole organisms. This not only promises to make toxicity testing faster, less expensive, and more humane, but also promises to generate more informative data. Toxicogenomics, the measurement of 'omics data such as transcriptomics, proteomics, and metabolomics in the context of toxicology, is key to realizing this goal. However, toxicogenomics data is extremely complex and the lack of computing resources, programming skills, advanced statistical training, and knowledge of bioinformatics databases presents barriers to many researchers and regulators. The barriers are particularly pronounced for environmental toxicologists using ecologically relevant species, as there are few bioinformatics resources outside of a small number of model organisms. The objective of this thesis is to design new statistical methods and corresponding software for analyzing and visualizing toxicogenomics data to support decision-making in the context of environmental toxicology. Many of the additional barriers to using transcriptomics data in ecologically relevant non-model organisms are related to raw data processing and annotation. Chapter 3 presents a set of computational tools (EcoOmicsAnalyst, ExpressAnalyst, EcoOmicsDB) for producing and analyzing annotated counts tables from raw RNA-seq data from any species, regardless of whether there is a reference genome. Traditional transcriptomics results such as lists of impacted genes and pathways are difficult to integrate into regulatory decision-making processes. Chapter 4 presents EcoToxModules, custom gene sets for summarizing and communicating transcriptomics data that are focused on toxicologically relevant biological processes. Chapter 5 presents FastBMD, software for performing rapid transcriptomics dose-response modeling. Since dose-response results such as benchmark dose values and points-of-departure are already familiar to the toxicology community, this type of analysis is useful because it translates unfamiliar toxicogenomics data into the familiar dose-response framework. Finally, while the cost of acquiring whole-transcriptome data has decreased tremendously over the last few decades, it is still outside the scope of many research programs. EcoToxChips are qPCR arrays with 384 genes for six ecologically relevant species that address this issue because qPCR technology is cost-effective with widespread availability. Chapter 6 presents EcoToxXplorer, software focused on EcoToxChip data processing, analysis, and interpretation. Together, the chapters in this thesis aim to support the use of toxicogenomics data in decision-making processes by making it more usable and understandable to individual members of the toxicology community, while also enabling standardized workflows that can be easily accessed by many different people in different locations. One important aspect of this is that all software presented in this thesis are web-based, which means that they do not require users to have substantial computing resources or programming skills, and do not require local installation. Throughout statistical method and software development, a design-thinking framework was used to continuously obtain and incorporate feedback from a large group of stakeholders and potential end-users from academia, government, and industry"--

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment
Author: National Research Council
Publisher: National Academies Press
Total Pages: 300
Release: 2007-12-19
Genre: Science
ISBN: 0309112982

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The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.

Communicating Toxicogenomics Information to Nonexperts

Communicating Toxicogenomics Information to Nonexperts
Author: National Research Council
Publisher: National Academies Press
Total Pages: 60
Release: 2005-05-14
Genre: Science
ISBN: 0309095387

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Toxicogenomics, the study of how genomes respond to exposure to toxicants, may ultimately hold the promise of detecting changes in the expression of a person's genes if he or she is exposed to these toxicants. As the technology rapidly develops, it is critical that scientists and the public communicate about the promises and limitations of this new field. Communicating technical information to the public about a developing science can be challenging, particularly when the applications of that science are not yet well understood. Communicating Toxicogenomics Information to Nonexperts is the summary of a workshop designed to consider strategies for communicating toxicogenomic information to the public and other non- expert audiences, specifically addressing the communication of some key social, ethical, and legal issues related to toxicogenomics and addressing how information related to the social implications of toxicogenomics might be perceived by nonexperts.

Science and Decisions

Science and Decisions
Author: National Research Council
Publisher: National Academies Press
Total Pages: 422
Release: 2009-03-24
Genre: Political Science
ISBN: 0309120462

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Risk assessment has become a dominant public policy tool for making choices, based on limited resources, to protect public health and the environment. It has been instrumental to the mission of the U.S. Environmental Protection Agency (EPA) as well as other federal agencies in evaluating public health concerns, informing regulatory and technological decisions, prioritizing research needs and funding, and in developing approaches for cost-benefit analysis. However, risk assessment is at a crossroads. Despite advances in the field, risk assessment faces a number of significant challenges including lengthy delays in making complex decisions; lack of data leading to significant uncertainty in risk assessments; and many chemicals in the marketplace that have not been evaluated and emerging agents requiring assessment. Science and Decisions makes practical scientific and technical recommendations to address these challenges. This book is a complement to the widely used 1983 National Academies book, Risk Assessment in the Federal Government (also known as the Red Book). The earlier book established a framework for the concepts and conduct of risk assessment that has been adopted by numerous expert committees, regulatory agencies, and public health institutions. The new book embeds these concepts within a broader framework for risk-based decision-making. Together, these are essential references for those working in the regulatory and public health fields.

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment
Author: National Research Council
Publisher: National Academies Press
Total Pages: 300
Release: 2007-11-19
Genre: Science
ISBN: 0309178894

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The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysâ€"an effort requiring funding, interagency coordination, and data management strategies.

Green Toxicology

Green Toxicology
Author: Alexandra Maertens
Publisher: Royal Society of Chemistry
Total Pages: 225
Release: 2022-02-01
Genre: Science
ISBN: 1839164409

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Green toxicology is an integral part of green chemistry. One of the key goals of green chemistry is to design less toxic chemicals. Therefore, an understanding of toxicology and hazard assessment is important for any chemist working in green chemistry, but toxicology is rarely part of most chemists' education. As a consequence, chemists lack the toxicological lens necessary to view chemicals in order to design safer substitutions. This book seeks to fill that gap and demonstrate how a basic understanding of toxicology, as well as the tools of in silico and in vitro toxicology, can be an integral part of green chemistry. R&D chemists, product stewards, and toxicologists who work in the field of sustainability, can all benefit from integrating green toxicology principles into their work. Topics include in silico tools for hazard assessment, toxicity testing, and lifecycle considerations, this book aims to act as a bridge between green toxicologists and green chemists.

Toxicity Testing in the 21st Century

Toxicity Testing in the 21st Century
Author: National Research Council
Publisher: National Academies Press
Total Pages: 217
Release: 2007-10-05
Genre: Nature
ISBN: 0309109922

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Advances in molecular biology and toxicology are paving the way for major improvements in the evaluation of the hazards posed by the large number of chemicals found at low levels in the environment. The National Research Council was asked by the U.S. Environmental Protection Agency to review the state of the science and create a far-reaching vision for the future of toxicity testing. The book finds that developing, improving, and validating new laboratory tools based on recent scientific advances could significantly improve our ability to understand the hazards and risks posed by chemicals. This new knowledge would lead to much more informed environmental regulations and dramatically reduce the need for animal testing because the new tests would be based on human cells and cell components. Substantial scientific efforts and resources will be required to leverage these new technologies to realize the vision, but the result will be a more efficient, informative and less costly system for assessing the hazards posed by industrial chemicals and pesticides.

An Introduction to Aquatic Toxicology

An Introduction to Aquatic Toxicology
Author: Mikko Nikinmaa
Publisher: Elsevier
Total Pages: 253
Release: 2014-07-01
Genre: Science
ISBN: 0124115810

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An Introduction to Aquatic Toxicology is an introductory reference for all aspects of toxicology pertaining to aquatic environments. As water sources diminish, the need to understand the effects that contaminants may have on aquatic organisms and ecosystems increases in importance. This book will provide you with a solid understanding of aquatic toxicology, its past, its cutting-edge present and its likely future. An Introduction to Aquatic Toxicology will introduce you to the global issue of aquatic contamination, detailing the major sources of contamination, from where they originate, and their effects on aquatic organisms and their environment. State-of-the-art toxicological topics covered include nanotoxicology, toxicogenomics, bioinformatics, transcriptomics, metabolomics, as well as water management and the toxicological effects of major environmental issues such as algal blooms, climate change and ocean acidification. This book is intended for anyone who wants to know more about the impact of toxicants on aquatic organisms and ecosystems, or to keep up to date with recent and future developments in the field. Provides with the latest perspectives on the impacts of toxicants on aquatic environments, such as nanotoxicology, toxicogenomics, ocean acidification and eutrophication Offers a complete overview, beginning with the origins of aquatic toxicology and concluding with potential future challenges Includes guidance on testing methods and a glossary of aquatic toxicology terms

Predictive Analytics for Toxicology

Predictive Analytics for Toxicology
Author: Luis G. Valerio, Jr.
Publisher: CRC Press
Total Pages: 253
Release: 2024-08-13
Genre: Science
ISBN: 1040101836

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Predictive data science is already in use in many fields, but its application in toxicology is new and sought after by non-animal alternative testing initiatives. Predictive Analytics for Toxicology: Applications in Discovery Science provides a comprehensive overview of the application of predictive analytics in the field of toxicology, highlighting its role and applications in discovery science. This book addresses the challenges of accurately predicting high-level endpoints of toxicity and explores the use of computational and artificial intelligence research to automate predictive toxicology. It underscores the importance of predictive toxicology in proposing and explaining adverse outcomes resulting from human exposures to specific toxicants, especially when experimental and observational data on the toxicant are incomplete or unavailable. Key features: Includes a plain language description of predictive analytics in toxicology adding an overview of the wide range of applications Examines the science of prediction, computational models as an automated science and comprehensive discussions on concepts of machine learning Opens the hood on AI and its applications in toxicology Features coverage on how in silico toxicity predictions are translational science tools The book integrates strategies and practices of predictive toxicology and offers practical information that students and professionals of the toxicology, chemical, and pharmaceutical industries will find essential. It fulfills the expectations of student researchers seeking to learn predictive analytics in toxicology. This book will energize scientists to conduct predictive toxicology modeling using artificial intelligence and machine learning, and inspire students and seasoned scientists interested in automated science to pick up new research using predictive in silico models to evaluate chemical-induced toxicity. With its focus on practical applications and real-world examples, this book serves as a guide for navigating the complex issues and practices of discovery toxicology. It is an essential resource for those interested in computer-based methods in toxicology, providing valuable insights into the use of predictive analytics.

Chemometrics and Cheminformatics in Aquatic Toxicology

Chemometrics and Cheminformatics in Aquatic Toxicology
Author: Kunal Roy
Publisher: John Wiley & Sons
Total Pages: 596
Release: 2022-01-06
Genre: Science
ISBN: 1119681596

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CHEMOMETRICS AND CHEMINFORMATICS IN AQUATIC TOXICOLOGY Explore chemometric and cheminformatic techniques and tools in aquatic toxicology Chemometrics and Cheminformatics in Aquatic Toxicology delivers an exploration of the existing and emerging problems of contamination of the aquatic environment through various metal and organic pollutants, including industrial chemicals, pharmaceuticals, cosmetics, biocides, nanomaterials, pesticides, surfactants, dyes, and more. The book discusses different chemometric and cheminformatic tools for non-experts and their application to the analysis and modeling of toxicity data of chemicals to various aquatic organisms. You’ll learn about a variety of aquatic toxicity databases and chemometric software tools and webservers as well as practical examples of model development, including illustrations. You’ll also find case studies and literature reports to round out your understanding of the subject. Finally, you’ll learn about tools and protocols including machine learning, data mining, and QSAR and ligand-based chemical design methods. Readers will also benefit from the inclusion of: A thorough introduction to chemometric and cheminformatic tools and techniques, including machine learning and data mining An exploration of aquatic toxicity databases, chemometric software tools, and webservers Practical examples and case studies to highlight and illustrate the concepts contained within the book A concise treatment of chemometric and cheminformatic tools and their application to the analysis and modeling of toxicity data Perfect for researchers and students in chemistry and the environmental and pharmaceutical sciences, Chemometrics and Cheminformatics in Aquatic Toxicology will also earn a place in the libraries of professionals in the chemical industry and regulators whose work involves chemometrics.