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.
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
SELECTION OF SURROGATE ANIMAL SPECIES FOR COMPARATIVE TOXICOGENOMICS
Brief Review on Studies Using Comparative Genomics
Selection Criteria for Surrogate Species
Selection of Surrogate Species
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?
BIOINFORMATIC APPROACHES AND COMPUTATIONAL MODELS FOR DATA INTEGRATION AND CROSS-SPECIES EXTRAPOLATION IN THE POST-GENOMIC ERA
Mechanistic vs. Classification Studies
Computational Methods for Ortholog Identification
Interpreting Expression Data Across Species
Integrating Data Across Domains
Supervised and Unsupervised Analysis for Toxicogenomics
The Problem of Validation
Recommendations for Advancing the Field
THE EXTENSION OF MOLECULAR AND COMPUTATIONAL INFORMATION TO RISK ASSESSMENT AND REGULATORY DECISION-MAKING
Overview of Human and Ecological Risk Assessment
Potential of 'Omics to Improve Risk Assessment
The Path Forward?
Conclusions and Recommendations