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EMERGING MOLECULAR COMPUTATIONAL APPROACHES FOR CROSS-SPECIES EXTRAPOLATIONS: A WORKSHOP SUMMARY
Citation:
Benson, W H. AND R. DiGuilio. EMERGING MOLECULAR COMPUTATIONAL APPROACHES FOR CROSS-SPECIES EXTRAPOLATIONS: A WORKSHOP SUMMARY. National Academy of Sciences, WASHINGTON, DC, 2004.
Description:
Advances in molecular technology have led to the elucidation of full genomic sequences of several multicellular organisms, ranging from nematodes to man. The related molecular field of proteomics and metabolomics are now beginning to advance rapidly as well. In addition, advances in bioinformatics and mathematical modeling provide powerful approaches for elucidating patterns of biological response imbedded in the massive data sets produced during genomics research. Thus, changes or differences in the expression patterns of entire genomes at the levels of mRNA, protein and metabolism can be assessed rapidly. Collectively, these emerging approaches may greatly enhance our ability to address many of the major issues in human and environmental toxicology. Specifically, they are uniquely qualified to address the issue of cross-species extrapolation in risk assessment in both human and environmental toxicology. Although there may be important differences in the genomes and proteomes among species, many of the responses to various stressors are evolutionarily conserved. For example, consider how fish, birds, and mammalian species respond to external stressors, including chemical toxicants (both synthetic and natural), genotoxicants (carcinogenic or mutagenic), or parasites. Stressed organisms can initiate both defensive and offensive actions to counteract adverse responses. Many of these defensive responses to external stimuli are common to many organisms, including wildlife species (fish, birds, invertebrates) and humans. Genomic technologies may provide great insight into how diverse organisms respond to environmental stressors. Motivated by these concerns, the Society of Environmental Toxicology and Chemistry (SETAC) and the Society of Toxicology (SOT) jointly sponsored a workshop entitled "Emerging Molecular and Computational Approaches for Cross-Species Extrapolations" in Forest Grove, Oregon, USA from 19 to 22 July 2004. This workshop was significant because leading societies - concerned on the one hand with the integrity of the environment (SETAC) and on the other hand with the improvement of human health (SOT) - worked together. Thirty-five scientists and professionals were brought together from diverse fields including environmental toxicology and chemistry, biomedical toxicology, molecular biology, genetics, physiology, bioinformatics, computer science and statistics. Such collaboration provided an ideal vehicle for objective and balanced discussion of this topic among professionals from different yet highly inter-related disciplines. The overall goal of the workshop was to outline a research agenda utilizing emerging technologies in genomics and computational biology in order to: 1) elucidate similarities and differences among species, 2) relate stressor-mediated responses to adverse outcomes, and 3) extend this science into innovative approaches to risk assessment and regulatory decisionmaking. Workshop participants identified specific research gaps and emerging issues. Key conclusions and recommendations of the workshop were: - Genomic technologies provide powerful research tools, but are currently insufficient as a basis for risk assessment and replacement of traditional approaches. - Perform collaborative proof of concept studies to improve our understanding of cross-species extrapolation by characterizing similarities and differences in metabolic pathways. - Develop more standardized approaches for omics technologies and associated data analysis. - Develop genomic databases for selected surrogate species, focusing on basic conserved cellular and physiologic processes. - Perform studies to validate relationship between omics responses and adverse biological outcomes. - Form a standing task force for cross-species/genomic issues. - Enhance training in genomic technologies, particularly within the context of an interdisciplinary approach. All relevant discussions and conclusions from the workshop will be published in a book edited by William H. Benson and Richard T. Di Giulio, and published through SETAC Press as was a previous SETAC-SOT Workshop which focused on interconnections between human health and ecological integrity (Di Giulio and Benson, 2002). The conclusions and recommendations from the 2002 Workshop on human health-ecological integrity served as the basis for the workshop on computational approaches and cross-species extrapolations. Di Giulio, R.T. and W.H. Benson (eds). 2002. Interconnections Between Human Health and Ecological Integrity. SETAC Press, Pensacola, FL.