Publication related to RSI or an RSI staff member
Technical guide for applications of gene expression profiling in human health risk assessment of environmental chemicals.
Toxicogenomics promises to be an important part of future human health risk assessment of environmental chemicals. The application of gene expression profiles (e.g., for hazard identification, chemical prioritization, chemical grouping, mode of action discovery, and quantitative analysis of response) is growing in the literature, but their use in formal risk assessment by regulatory agencies is relatively infrequent. Although additional validations for specific applications are required, gene expression data can be of immediate use for increasing confidence in chemical evaluations. We believe that a primary reason for the current lack of integration is the limited practical guidance available for risk assessment specialists with limited experience in genomics. The present manuscript provides basic information on gene expression profiling, along with guidance on evaluating the quality of genomic experiments and data, and interpretation of results presented in the form of heat maps, pathway analyses and other common approaches. Moreover, potential ways to integrate information from gene expression experiments into current risk assessment are presented using published studies as examples. The primary objective of this work is to facilitate integration of gene expression data into human health risk assessments of environmental chemicals.
Authors
- Bourdon-Lacombe, Julie A, Bourdon-Lacombe JA, Water and Air Quality Bureau, Health Canada, Ottawa, ON, Canada.
- Moffat, Ivy D, Moffat ID, Water and Air Quality Bureau, Health Canada, Ottawa, ON, Canada. Electronic address: Ivy.Moffat@hc-sc.gc.ca.
- Deveau, Michelle, Deveau M, Water and Air Quality Bureau, Health Canada, Ottawa, ON, Canada.
- Husain, Mainul, Husain M, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
- Auerbach, Scott, Auerbach S, Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
- Krewski, Daniel, Krewski D, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, ON, Canada.
- Thomas, Russell S, Thomas RS, National Centre for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States.
- Bushel, Pierre R, Bushel PR, Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
- Williams, Andrew, Williams A, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
- Yauk, Carole L, Yauk CL, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada.
Toxicogenomics promises to be an important part of future human health risk assessment of environmental chemicals. The application of gene expression profiles (e.g., for hazard identification, chemical prioritization, chemical grouping, mode of action discovery, and quantitative analysis of response) is growing in the literature, but their use in formal risk assessment by regulatory agencies is relatively infrequent. Although additional validations for specific applications are required, gene expression data can be of immediate use for increasing confidence in chemical evaluations. We believe that a primary reason for the current lack of integration is the limited practical guidance available for risk assessment specialists with limited experience in genomics. The present manuscript provides basic information on gene expression profiling, along with guidance on evaluating the quality of genomic experiments and data, and interpretation of results presented in the form of heat maps, pathway analyses and other common approaches. Moreover, potential ways to integrate information from gene expression experiments into current risk assessment are presented using published studies as examples. The primary objective of this work is to facilitate integration of gene expression data into human health risk assessments of environmental chemicals.
