1st Edition

Genomic Approaches for Cross-Species Extrapolation in Toxicology

Edited By William H. Benson, Richard T. Di Giulio Copyright 2007
    216 Pages 16 B/W Illustrations
    by CRC Press

    The latest tools for investigating stress response in organisms, genomic technologies provide great insight into how different organisms respond to environmental conditions. However, their usefulness needs to be tested, verified, and codified. Genomic Approaches for Cross-Species Extrapolation in Toxicology provides a balanced discussion drawn from the experience of thirty-five scientists and professionals from diverse fields including environmental toxicology and chemistry, biomedical toxicology, molecular biology, genetics, physiology, bioinformatics, computer science, and statistics.

    The book introduces genomic, transcriptomic, proteomic, and metabolomic technologies. It describes the advantages and challenges associated with these approaches compared to traditional methodologies, particularly from the perspective of cross-species extrapolation within human and environmental toxicology, and explores solutions that will facilitate the incorporation of these technologies into predictive toxicology. The book goes on to identify and prioritize species of animals that can serve as surrogates for environmental and human health in comparative toxicogenomic studies. The chapter authors elucidate similarities and differences among species, relate stressor-mediated responses to adverse outcomes, and extend this science into innovative approaches to risk assessment and regulatory decision-making.

    "OMIC" APPROACHES IN THE CONTEXT OF ENVIRONMENTAL TOXICOLOGY
    Introduction
    Overview of Omic Technologies
    Discovery-Driven Versus Hypothesis-Driven Research: A Need for Balance
    Advantages, Challenges, and Solutions of Omic Technologies
    Pathway Mapping - The Future of Omic Technologies
    An Example of Cross Species Extrapolation Using Transcriptomics
    Recommendations
    Future
    References

    SELECTION OF SURROGATE ANIMAL SPECIES FOR COMPARATIVE TOXICOGENOMICS
    Introduction
    Brief Review on Studies Using Comparative Genomics
    Selection Criteria for Surrogate Species
    Selection of Surrogate Species
    Discussion
    Conclusions
    References

    SPECIES DIFFERENCES IN RESPONSE TO TOXIC SUBSTANCES: SHARED PATHWAYS OF TOXICITY
    What Omics Approaches Would be of Greatest Value in Predictive Toxicology that Utilizes Biologically Relevant Effects in Organisms or the Environment?
    How Can Omics be Utilized to Understand Mechanism and/or Mode of Action?
    How do we Integrate Responses Across Gene Expression, Proteomics, and Metabolomics and Apply this to Make a Science-Based Statement About the Health of an Organism?
    How Does Development of Omic Technologies Impact the Interspecies Extrapolation Process?
    What are the Key Limitations/Considerations in Using Omics Technologies to Inform Mechanism of Cross-Species Differences in Response to Xenobiotics?
    Conclusions
    Recommendations

    BIOINFORMATIC APPROACHES AND COMPUTATIONAL MODELS FOR DATA INTEGRATION AND CROSS-SPECIES EXTRAPOLATION IN THE POST-GENOMIC ERA
    Introduction
    Mechanistic vs. Classification Studies
    Computational Methods for Ortholog Identification
    Interpreting Expression Data Across Species
    Integrating Data Across Domains
    Supervised and Unsupervised Analysis for Toxicogenomics
    Networks
    The Problem of Validation
    Predictive Toxicology
    Recommendations for Advancing the Field
    Concluding Remarks
    References

    THE EXTENSION OF MOLECULAR AND COMPUTATIONAL INFORMATION TO RISK ASSESSMENT AND REGULATORY DECISION-MAKING
    Introduction
    Overview of Human and Ecological Risk Assessment
    Potential of 'Omics to Improve Risk Assessment
    The Path Forward?
    Conclusions and Recommendations
    Acknowledgements
    References

    Biography

    William H. Benson, Richard T. Di Giulio