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Developing Network-Based Systems Toxicology by Combining Transcriptomics Data with Literature Mining and Multiscale Quantitative Modeling

Developing Network-Based Systems Toxicology by Combining Transcriptomics Data with Literature Mining and Multiscale Quantitative Modeling
Author: Alain Sewer
Publisher:
Total Pages:
Release: 2018
Genre: Medicine
ISBN:

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We describe how the genome-wide transcriptional profiling can be used in network-based systems toxicology, an approach leveraging biological networks for assessing the health risks of exposure to chemical compounds. Driven by the technological advances changing the ways in which data are generated, systems toxicology has allowed traditional toxicity endpoints to be enhanced with far deeper levels of analysis. In combination, new experimental and computational methods have offered the potential for more effective, efficient, and reliable toxicological testing strategies. We illustrate these advances by the "network perturbation amplitude" methodology that quantifies the effects of exposure treatments on biological mechanisms represented by causal networks. We also describe recent developments in the assembly of high-quality causal biological networks using crowdsourcing and text-mining approaches. We further show how network-based approaches can be integrated into the multiscale modeling framework of response to toxicological exposure. Finally, we combine biological knowledge assembly and multiscale modeling to report on the promising developments of the "quantitative adverse outcome pathway" concept, which spans multiple levels of biological organization, from molecules to population, and has direct relevance in the context of the "Toxicity Testing in the 21st century" vision of the US National Research Council.


Bioinformatics in the Era of Post Genomics and Big Data

Bioinformatics in the Era of Post Genomics and Big Data
Author: Ibrokhim Y. Abdurakhmonov
Publisher: BoD – Books on Demand
Total Pages: 190
Release: 2018-06-20
Genre: Medical
ISBN: 1789232686

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Bioinformatics has evolved significantly in the era of post genomics and big data. Huge advancements were made toward storing, handling, mining, comparing, extracting, clustering and analysis as well as visualization of big macromolecular data using novel computational approaches, machine and deep learning methods, and web-based server tools. There are extensively ongoing world-wide efforts to build the resources for regional hosting, organized and structured access and improving the pre-existing bioinformatics tools to efficiently and meaningfully analyze day-to-day increasing big data. This book intends to provide the reader with updates and progress on genomic data analysis, data modeling and network-based system tools.


Quantitative Modeling in Toxicology

Quantitative Modeling in Toxicology
Author: Kannan Krishnan
Publisher: John Wiley & Sons
Total Pages: 504
Release: 2010-04-01
Genre: Science
ISBN: 0470686707

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Governments around the world are passing laws requiring industry to assess the toxicity of the chemicals and products they produce, but to do so while reducing, refining, or even replacing testing on animals. To meet these requirements, experimental toxicologists and risk assessors are adopting quantitative approaches and computer simulations to study the biological fate and effects of chemicals and drugs. In Quantitative Modeling in Toxicology leading experts outline the current state of knowledge on the modeling of dose, tissue interactions and tissue responses. Each chapter describes the mathematical foundation, parameter estimation, challenges and perspectives for development, along with the presentation of a modeling template. Additionally, tools and approaches for conducting uncertainty, sensitivity and variability analyses in these models are described. Topics covered include: the quantitative models of pharmacokinetics of individual chemicals and mixtures models for toxicant-target tissue interaction. models for cellular, organ, and organism responses. approaches, tools and challenges for model application and evaluation A website containing computer codes accompanies the book to help the reader reconstruct the models described and discussed in the various chapters. Quantitative Modeling in Toxicology serves as an essential reference source and tool box for risk assessors and researchers and students in toxicology, public health, pharmacology, and human toxicology interested in developing quantitative models for a better understanding of dose-response relationships.


Advances in Computational Toxicology

Advances in Computational Toxicology
Author: Huixiao Hong
Publisher: Springer
Total Pages: 412
Release: 2019-05-21
Genre: Science
ISBN: 3030164438

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This book provides a comprehensive review of both traditional and cutting-edge methodologies that are currently used in computational toxicology and specifically features its application in regulatory decision making. The authors from various government agencies such as FDA, NCATS and NIEHS industry, and academic institutes share their real-world experience and discuss most current practices in computational toxicology and potential applications in regulatory science. Among the topics covered are molecular modeling and molecular dynamics simulations, machine learning methods for toxicity analysis, network-based approaches for the assessment of drug toxicity and toxicogenomic analyses. Offering a valuable reference guide to computational toxicology and potential applications in regulatory science, this book will appeal to chemists, toxicologists, drug discovery and development researchers as well as to regulatory scientists, government reviewers and graduate students interested in this field.


Multiscale Toxicology

Multiscale Toxicology
Author:
Publisher:
Total Pages:
Release: 2012
Genre:
ISBN:

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Network Pharmacology

Network Pharmacology
Author: Shao Li
Publisher: Springer Nature
Total Pages: 480
Release: 2021-09-29
Genre: Medical
ISBN: 9811607532

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This book introduces “network pharmacology” as an emerging frontier subject of systematic drug research in the era of artificial intelligence and big data. Network Pharmacology is an original subject of fusion system biology, bioinformatics, network science and other related disciplines. It emphasizes on starting from the overall perspective of the system level and biological networks, the analysis of the laws of molecular association between drugs and their treatment objects, reveals the systematic pharmacological mechanisms of drugs, and guides the research and development of new drugs and clinical diagnosis and treatment. After it was proposed, network pharmacology has been paid attention by researchers, and it has been rapidly developed and widely used. In order to systematically reveal the biological basis of diagnosis and treatment in traditional Chinese medicine and modern medicine, we proposed a new concept of "network target" for the first time, which has become the core theory of "network pharmacology". The core principle of a network target is to construct a biological network that can be used to decipher complex diseases. The network is then used as the therapeutic target, to which multicomponent remedies are applied. This book mainly includes four parts: 1) The concept and theory of network pharmacology; 2) Common analysis methods, databases and software in network pharmacological research; 3) Typical cases of traditional Chinese medicine modernization and modern drug research based on network pharmacology; 4) Network pharmacology practice process based on drugs and diseases.


In Silico Toxicology

In Silico Toxicology
Author: Mark T. D. Cronin
Publisher: Royal Society of Chemistry
Total Pages: 689
Release: 2010
Genre: Medical
ISBN: 1849730040

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This book defines the use of computational approaches to predict the environmental toxicity and human health effects of organic chemicals.


Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications, Third Edition

Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications, Third Edition
Author: Johan Gabrielsson
Publisher: CRC Press
Total Pages: 926
Release: 2001-11-30
Genre: Medical
ISBN: 9789186274924

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This is a revised and very expanded version of the previous second edition of the book. "Pharmacokinetic and Pharmacodynamic Data Analysis" provides an introduction into pharmacokinetic and pharmacodynamic concepts using simple illustrations and reasoning. It describes ways in which pharmacodynamic and pharmacodynamic theory may be used to give insight into modeling questions and how these questions can in turn lead to new knowledge. This book differentiates itself from other texts in this area in that it bridges the gap between relevant theory and the actual application of the theory to real life situations. The book is divided into two parts; the first introduces fundamental principles of PK and PD concepts, and principles of mathematical modeling, while the second provides case studies obtained from drug industry and academia. Topics included in the first part include a discussion of the statistical principles of model fitting, including how to assess the adequacy of the fit of a model, as well as strategies for selection of time points to be included in the design of a study. The first part also introduces basic pharmacokinetic and pharmacodynamic concepts, including an excellent discussion of effect compartment (link) models as well as indirect response models. The second part of the text includes over 70 modeling case studies. These include a discussion of the selection of the model, derivation of initial parameter estimates and interpretation of the corresponding output. Finally, the authors discuss a number of pharmacodynamic modeling situations including receptor binding models, synergy, and tolerance models (feedback and precursor models). This book will be of interest to researchers, to graduate students and advanced undergraduate students in the PK/PD area who wish to learn how to analyze biological data and build models and to become familiar with new areas of application. In addition, the text will be of interest to toxicologists interested in learning about determinants of exposure and performing toxicokinetic modeling. The inclusion of the numerous exercises and models makes it an excellent primary or adjutant text for traditional PK courses taught in pharmacy and medical schools. A diskette is included with the text that includes all of the exercises and solutions using WinNonlin.


Health and Environmental Safety of Nanomaterials

Health and Environmental Safety of Nanomaterials
Author: James Njuguna
Publisher: Elsevier
Total Pages: 345
Release: 2014-02-15
Genre: Technology & Engineering
ISBN: 0857096672

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Health and Environmental Safety of Nanomaterials addresses concerns about the impact of nanomaterials on the environment and human health, and examines the safety of specific nanomaterials. Understanding the unique chemical and physical properties of nanostructures has led to many developments in the applications of nanocomposite materials. While these materials have applications in a huge range of areas, their potential for toxicity must be thoroughly understood. Part one introduces the properties of nanomaterials, nanofillers, and nanocomposites, and questions whether they are more toxic than their bulk counterparts. Part two looks at the release and exposure of nanomaterials. The text covers sampling techniques and data analysis methods used to assess nanoparticle exposure, as well as protocols for testing the safety of polymer nanocomposites. It explains characterization techniques of airborne nanoparticles and life cycle assessment of engineered nanomaterials. Part three focuses on the safety of certain nanomaterials, including nanolayered silicates, carbon nanotubes, and metal oxides. In particular, it explores the potential ecotoxicological hazards associated with the different structures of carbon nanotubes and the safe recycling of inorganic and carbon nanoparticles. The final two chapters address the risks of nanomaterials in fire conditions: their thermal degradation, flammability, and toxicity in different fire scenarios. This is a scientific guide with technical background for professionals using nanomaterials in industry, scientists, academicians, research scholars, and polymer engineers. It also offers a deep understanding of the subject for undergraduate and postgraduate students. Introduces the properties of nanomaterials, nanofillers, and nanocomposites, and questions whether they are more toxic than their bulk counterparts Covers sampling techniques and data analysis methods used to assess nanoparticle exposure, as well as protocols for testing the safety of polymer nanocomposites Explores the potential ecotoxicological hazards associated with the different structures of carbon nanotubes and the safe recycling of inorganic and carbon nanoparticles


The Exposome

The Exposome
Author: Gary W. Miller
Publisher: Elsevier
Total Pages: 118
Release: 2013-11-16
Genre: Science
ISBN: 0124172180

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The Exposome: A Primer is the first book dedicated to exposomics, detailing the purpose and scope of this emerging field of study, its practical applications and how it complements a broad range of disciplines. Genetic causes account for up to a third of all complex diseases. (As genomic approaches improve, this is likely to rise.) Environmental factors also influence human disease but, unlike with genetics, there is no standard or systematic way to measure the influence of environmental exposures. The exposome is an emerging concept that hopes to address this, measuring the effects of life-long environmental exposures on health and how these exposures can influence disease. This systematic introduction considers topics of managing and integrating exposome data (including maps, models, computation, and systems biology), "-omics"-based technologies, and more. Both students and scientists in disciplines including toxicology, environmental health, epidemiology, and public health will benefit from this rigorous yet readable overview.