Validation of Toxicogenomic Technologies: A Workshop Summary (2007)
Chapter: Front Matter
VALIDATION OF TOXICOGENOMIC TECHNOLOGIES
A Workshop Summary
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This project was supported by Contract No. G-NAG 9-1451 between the National Academy of Sciences and the National Aeronautics and Space Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
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COMMITTEE ON VALIDATION OF TOXICOGENOMIC TECHNOLOGIES:A FOCUS ON CHEMICALCLASSIFICATION STRATEGIES
Members
JOHNQUACKENBUSH(Co-Chair),
Harvard School of Public Health, Boston, MA
KENNETHS. RAMOS(Co-Chair),
University of Louisville, KY
CYNTHIAA. AFSHARI,
Amgen, Inc., Thousand Oaks, Louisville, CA
LINDAE. GREER,
Natural Resources Defense Council, Washington, DC
CASIMIRA. KULIKOWSKI,
Rutgers University, New Brunswick, NJ
GEORGEORPHANIDES,
Syngenta Central Toxicology Laboratory, Cheshire, UK
LAWRENCEM. SUNG,
University of Maryland School of Law, Baltimore, MD
RUSSELLD. WOLFINGER,
SAS Institute Inc., Cary, NC
Staff
KARLE. GUSTAVSON, Project Director
MARILEEK. SHELTON-DAVENPORT, Project Director
JENNIFERE. SAUNDERS, Associate Program Officer
RUTHE. CROSSGROVE, Senior Editor
MIRSADAKARALIC-LONCAREVIC, Research Associate
RADIAHA. ROSE, Senior Editorial Assistant
LUCYV. FUSCO, Senior Project Assistant
Sponsor
NATIONALINSTITUTE OFENVIRONMENTALHEALTHSCIENCES
COMMITTEE ON EMERGING ISSUES AND DATA ONENVIRONMENTAL CONTAMINANTS
Members
KENNETHS. RAMOS(Chair),
University of Louisville, Louisville, KY
PATRICIAA. BUFFLER,
University of California, Berkeley
JAMESS. BUS,
Dow Chemical Company, Midland, MI
GREGORYJ. CARR,
The Procter & Gamble Company, Cincinnati, OH
JOSEPHJ. DEGEORGE,
Merck Research Laboratories, West Point, PA
DAVIDJ. GALAS,
Battelle Memorial Institute, Columbus, OH
LINDAE. GREER,
Natural Resources Defense Council, Washington, DC
ROBERTJ. GRIFFIN,
Marquette University, Milwaukee, WI
AMYD. KYLE,
University of California, Berkeley
PETERG. LORD,
Johnson & Johnson, Raritan, NJ
WILLIAMB. MATTES,
Critical Path Institute, Poolesville, MD
AUBREYMILUNSKY,
Boston University School of Medicine, Boston, MA
GILBERTS. OMENN,
University of Michigan Medical School, Ann Arbor
GEORGEORPHANIDES,
Syngenta Central Toxicology Laboratory, Cheshire, UK
FREDERICAP. PERERA,
Columbia University, New York, NY
JOHNQUACKENBUSH,
Harvard School of Public Health, Boston, MA
MARKA. ROTHSTEIN,
University of Louisville School of Medicine, Louisville, KY
LEONAD. SAMSON,
Massachusetts Institute of Technology, Cambridge
MARTHAS. SANDY,
California Environmental Protection Agency, Oakland
TODDSHERER,
Emory University, Atlanta, GA
PETERS. SPENCER,
Oregon Health and Science University, Portland
LAWRENCEM. SUNG,
University of Maryland, Baltimore
MAHLETG. TADESSE,
University of Pennsylvania School of Medicine, Philadelphia
CHERYLL. WALKER,
University of Texas, Smithville
Staff
KARLE. GUSTAVSON, Project Director
MARILEEK. SHELTON-DAVENPORT, Project Director
JENNIFERE. SAUNDERS, Associate Program Officer
RUTHE. CROSSGROVE, Senior Editor
RADIAHA. ROSE, Senior Editorial Assistant
LUCYV. FUSCO, Senior Project Assistant
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Members
JONATHANM. SAMET(Chair),
Johns Hopkins University, Baltimore, MD
RAMÓNALVAREZ,
Environmental Defense, Austin, TX
JOHNM. BALBUS,
Environmental Defense, Washington, DC
DALLASBURTRAW,
Resources for the Future, Washington, DC
JAMESS. BUS,
Dow Chemical Company, Midland, MI
COSTELD. DENSON,
University of Delaware, Newark
E. DONALDELLIOTT,
Willkie Farr & Gallagher LLP, Washington, DC
MARYR. ENGLISH,
University of Tennessee, Knoxville
J. PAULGILMAN,
Oak Ridge Center for Advanced Studies, Oak Ridge, TN
SHERRIW. GOODMAN,
Center for Naval Analyses, Alexandria, VA
JUDITHA. GRAHAM,
American Chemistry Council, Arlington, VA
WILLIAMP. HORN,
Birch, Horton, Bittner and Cherot, Washington, DC
JAMESH. JOHNSON, JR.,
Howard University, Washington, DC
WILLIAMM. LEWIS, JR.,
University of Colorado, Boulder
JUDITHL. MEYER,
University of Georgia, Athens
DENNISD. MURPHY,
University of Nevada, Reno
PATRICKY. O’BRIEN,
ChevronTexaco Energy Technology Company, Richmond, CA
DOROTHYE. PATTON (retired),
Chicago, IL
DANNYD. REIBLE,
University of Texas, Austin
JOSEPHV. RODRICKS,
ENVIRON International Corporation, Arlington, VA
ARMISTEADG. RUSSELL,
Georgia Institute of Technology, Atlanta
ROBERTF. SAWYER,
University of California, Berkeley
LISASPEER,
Natural Resources Defense Council, New York, NY
KIMBERLYM. THOMPSON,
Massachusetts Institute of Technology, Cambridge
MONICAG. TURNER,
University of Wisconsin, Madison
MARKJ. UTELL,
University of Rochester Medical Center, Rochester, NY
CHRISG. WHIPPLE,
ENVIRON International Corporation, Emeryville, CA
LAURENZEISE,
California Environmental Protection Agency, Oakland
Senior Staff
JAMESJ. REISA, Director
DAVIDJ. POLICANSKY, Scholar
RAYMONDA. WASSEL, Senior Program Officer for Environmental Sciences and Engineering
KULBIRBAKSHI, Senior Program Officer for Toxicology
EILEENN. ABT, Senior Program Officer for Risk Analysis
KARLE. GUSTAVSON, Senior Program Officer
K. JOHNHOLMES, Senior Program Officer
ELLENK. MANTUS, Senior Program Officer
SUSANN.J. MARTEL, Senior Program Officer
STEVENK. GIBB, Program Officer for Strategic Communications
RUTHE. CROSSGROVE, Senior Editor
BOARD ON LIFE SCIENCES
Members
KEITHYAMAMOTO(Chair),
University of California, San Francisco
ANNM. ARVIN,
Stanford University School of Medicine, Stanford, CA
JEFFREYL. BENNETZEN,
University of Georgia, Athens
RUTHBERKELMAN,
Emory University, Atlanta, GA
DEBORAHBLUM,
University of Wisconsin, Madison
R. ALTACHARO,
University of Wisconsin, Madison
JEFFREYL. DANGL,
University of North Carolina, Chapel Hill
PAULR. EHRLICH,
Stanford University, Stanford, CA
MARKD. FITZSIMMONS,
John D. and Catherine T. MacArthur Foundation, Chicago, IL
JOHANDELSMAN,
University of Wisconsin, Madison
EDHARLOW,
Harvard Medical School, Boston, MA
KENNETHH. KELLER,
University of Minnesota, Minneapolis
RANDALLMURCH,
Virginia Polytechnic Institute and State University, Alexandria
GREGORYA. PETSKO,
Brandeis University, Waltham, MA
MURIELE. POSTON,
Skidmore College, Saratoga Springs, NY
JAMESREICHMAN,
University of California, Santa Barbara
MARCT. TESSIER-LAVIGNE,
Genentech, Inc., San Francisco, CA
JAMESTIEDJE,
Michigan State University, East Lansing
TERRYL. YATES,
University of New Mexico, Albuquerque
Senior Staff
FRANCESE. SHARPLES, Director
KERRYA. BRENNER, Senior Program Officer
MARILEEK. SHELTON-DAVENPORT, Senior Program Officer
EVONNEP.Y. TANG, Senior Program Officer
ROBERTT. YUAN, Senior Program Officer
ADAMP. FAGEN, Program Officer
ANNH. REID, Senior Program Officer
ANNAFARRAR, Financial Associate
ANNEF. JURKOWSKI, Senior Program Assistant
TOVAG. JACOBOVITS, Senior Program Assistant
PREFACE
Toxicogenomics has been described as a discipline combining expertise in toxicology, genetics, molecular biology, and environmental health to elucidate the response of living organisms to stressful environments. It includes the study of how genomes respond to toxicant exposures and how genotype affects responses to toxicant exposures. As the technologies for monitoring these responses rapidly develop, it is critical that scientists and regulators are confident that the technologies are reliable and reproducible and that the data analyses have been validated. To discuss these issues in a public forum, the Committee on the Validation of Toxicogenomic Technologies designed a workshop to consider the current practice and advances in the validation of toxicogenomic technologies. The workshop focused on the technical aspects of validation, recognizing it as a prerequisite for considering other important issues, such as biological validation (e.g., validating the use of microarray “signatures” to describe a toxic effect).
This workshop summary has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s (NRC) Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published workshop summary as sound as possible and to ensure that the summary meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following people for their review of this workshop summary: Federico Goodsaid, William Mattes, Gavin Sherlock, and Mahlet Tadesse.
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the workshop summary before its release. The review of the workshop summary was overseen by Timothy R. Zacharewski, of Michigan State University. Appointed by the NRC, he was responsible for making certain that an independent examination of the workshop summary was carried out in accordance with institutional procedures and that all review com-
ments were carefully considered. Responsibility for the final content of the workshop summary rests entirely with the committee and the institution.
The committee gratefully acknowledges the following for making presentations at the workshop: Kevin K. Dobbin, National Cancer Institute; Hisham K. Hamadeh, Amgen, Inc.; Wherly P. Hoffman, Eli Lily & Company; Rafael A. Irizarry, Johns Hopkins University Bloomberg School of Public Health; Kyle L. Kolaja, Iconix Pharmaceuticals; Leonard M. Schechtman, Food and Drug Administration; Guido Steiner, F. Hoffmann-La Roche AG; and Weida Tong, FDA National Center for Toxicological Research.
The committee is grateful for the assistance of the NRC staff in preparing this workshop summary: Karl Gustavson and Marilee Shelton-Davenport, program directors; James Reisa, director of the Board on Environmental Studies and Toxicology; Fran Sharples, director of the Board on Life Sciences; Jennifer Saunders, associate program officer; Ruth Crossgrove, senior editor; Mirsada Karalic-Loncarevic, research associate; Radiah Rose, senior editorial assistant; and Lucy Fusco, program associate.
Finally, we thank the members of the committee for their dedicated efforts throughout the development of this workshop summary.
John Quackenbush
Kenneth S. Ramos
Co-Chairs, Committee on Validation of Toxicogenomic Technologies
