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.
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COMMITTEE ON VALIDATION OF TOXICOGENOMIC TECHNOLOGIES: A FOCUS ON CHEMICALCLASSIFICATION STRATEGIES
Members
JOHN QUACKENBUSH (Co-Chair),
Harvard School of Public Health, Boston, MA
KENNETH S. RAMOS (Co-Chair),
University of Louisville, KY
CYNTHIA A. AFSHARI,
Amgen, Inc., Thousand Oaks, Louisville, CA
LINDA E. GREER,
Natural Resources Defense Council, Washington, DC
CASIMIR A. KULIKOWSKI,
Rutgers University, New Brunswick, NJ
GEORGE ORPHANIDES,
Syngenta Central Toxicology Laboratory, Cheshire, UK
LAWRENCE M. SUNG,
University of Maryland School of Law, Baltimore, MD
RUSSELL D. WOLFINGER,
SAS Institute Inc., Cary, NC
Staff
KARL E. GUSTAVSON, Project Director
MARILEE K. SHELTON-DAVENPORT, Project Director
JENNIFER E. SAUNDERS, Associate Program Officer
RUTH E. CROSSGROVE, Senior Editor
MIRSADA KARALIC-LONCAREVIC, Research Associate
RADIAH A. ROSE, Senior Editorial Assistant
LUCY V. FUSCO, Senior Project Assistant
Sponsor
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
COMMITTEE ON EMERGING ISSUES AND DATA ON ENVIRONMENTAL CONTAMINANTS
Members
KENNETH S. RAMOS (Chair),
University of Louisville, Louisville, KY
PATRICIA A. BUFFLER,
University of California, Berkeley
JAMES S. BUS,
Dow Chemical Company, Midland, MI
GREGORY J. CARR,
The Procter & Gamble Company, Cincinnati, OH
JOSEPH J. DEGEORGE,
Merck Research Laboratories, West Point, PA
DAVID J. GALAS,
Battelle Memorial Institute, Columbus, OH
LINDA E. GREER,
Natural Resources Defense Council, Washington, DC
ROBERT J. GRIFFIN,
Marquette University, Milwaukee, WI
AMY D. KYLE,
University of California, Berkeley
PETER G. LORD,
Johnson & Johnson, Raritan, NJ
WILLIAM B. MATTES,
Critical Path Institute, Poolesville, MD
AUBREY MILUNSKY,
Boston University School of Medicine, Boston, MA
GILBERT S. OMENN,
University of Michigan Medical School, Ann Arbor
GEORGE ORPHANIDES,
Syngenta Central Toxicology Laboratory, Cheshire, UK
FREDERICA P. PERERA,
Columbia University, New York, NY
JOHN QUACKENBUSH,
Harvard School of Public Health, Boston, MA
MARK A. ROTHSTEIN,
University of Louisville School of Medicine, Louisville, KY
LEONA D. SAMSON,
Massachusetts Institute of Technology, Cambridge
MARTHA S. SANDY,
California Environmental Protection Agency, Oakland
TODD SHERER,
Emory University, Atlanta, GA
PETER S. SPENCER,
Oregon Health and Science University, Portland
LAWRENCE M. SUNG,
University of Maryland, Baltimore
MAHLET G. TADESSE,
University of Pennsylvania School of Medicine, Philadelphia
CHERYL L. WALKER,
University of Texas, Smithville
Staff
KARL E. GUSTAVSON, Project Director
MARILEE K. SHELTON-DAVENPORT, Project Director
JENNIFER E. SAUNDERS, Associate Program Officer
RUTH E. CROSSGROVE, Senior Editor
RADIAH A. ROSE, Senior Editorial Assistant
LUCY V. FUSCO, Senior Project Assistant
BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Members
JONATHAN M. SAMET (Chair),
Johns Hopkins University, Baltimore, MD
RAMÓN ALVAREZ,
Environmental Defense, Austin, TX
JOHN M. BALBUS,
Environmental Defense, Washington, DC
DALLAS BURTRAW,
Resources for the Future, Washington, DC
JAMES S. BUS,
Dow Chemical Company, Midland, MI
COSTEL D. DENSON,
University of Delaware, Newark
E. DONALD ELLIOTT,
Willkie Farr & Gallagher LLP, Washington, DC
MARY R. ENGLISH,
University of Tennessee, Knoxville
J. PAUL GILMAN,
Oak Ridge Center for Advanced Studies, Oak Ridge, TN
SHERRI W. GOODMAN,
Center for Naval Analyses, Alexandria, VA
JUDITH A. GRAHAM,
American Chemistry Council, Arlington, VA
WILLIAM P. HORN,
Birch, Horton, Bittner and Cherot, Washington, DC
JAMES H. JOHNSON, JR.,
Howard University, Washington, DC
WILLIAM M. LEWIS, JR.,
University of Colorado, Boulder
JUDITH L. MEYER,
University of Georgia, Athens
DENNIS D. MURPHY,
University of Nevada, Reno
PATRICK Y. O’BRIEN,
ChevronTexaco Energy Technology Company, Richmond, CA
DOROTHY E. PATTON (retired),
Chicago, IL
DANNY D. REIBLE,
University of Texas, Austin
JOSEPH V. RODRICKS,
ENVIRON International Corporation, Arlington, VA
ARMISTEAD G. RUSSELL,
Georgia Institute of Technology, Atlanta
ROBERT F. SAWYER,
University of California, Berkeley
LISA SPEER,
Natural Resources Defense Council, New York, NY
KIMBERLY M. THOMPSON,
Massachusetts Institute of Technology, Cambridge
MONICA G. TURNER,
University of Wisconsin, Madison
MARK J. UTELL,
University of Rochester Medical Center, Rochester, NY
CHRIS G. WHIPPLE,
ENVIRON International Corporation, Emeryville, CA
LAUREN ZEISE,
California Environmental Protection Agency, Oakland
Senior Staff
JAMES J. REISA, Director
DAVID J. POLICANSKY, Scholar
RAYMOND A. WASSEL, Senior Program Officer for Environmental Sciences and Engineering
KULBIR BAKSHI, Senior Program Officer for Toxicology
EILEEN N. ABT, Senior Program Officer for Risk Analysis
KARL E. GUSTAVSON, Senior Program Officer
K. JOHN HOLMES, Senior Program Officer
ELLEN K. MANTUS, Senior Program Officer
SUSAN N.J. MARTEL, Senior Program Officer
STEVEN K. GIBB, Program Officer for Strategic Communications
RUTH E. CROSSGROVE, Senior Editor
BOARD ON LIFE SCIENCES
Members
KEITH YAMAMOTO (Chair),
University of California, San Francisco
ANN M. ARVIN,
Stanford University School of Medicine, Stanford, CA
JEFFREY L. BENNETZEN,
University of Georgia, Athens
RUTH BERKELMAN,
Emory University, Atlanta, GA
DEBORAH BLUM,
University of Wisconsin, Madison
R. ALTA CHARO,
University of Wisconsin, Madison
JEFFREY L. DANGL,
University of North Carolina, Chapel Hill
PAUL R. EHRLICH,
Stanford University, Stanford, CA
MARK D. FITZSIMMONS,
John D. and Catherine T. MacArthur Foundation, Chicago, IL
JO HANDELSMAN,
University of Wisconsin, Madison
ED HARLOW,
Harvard Medical School, Boston, MA
KENNETH H. KELLER,
University of Minnesota, Minneapolis
RANDALL MURCH,
Virginia Polytechnic Institute and State University, Alexandria
GREGORY A. PETSKO,
Brandeis University, Waltham, MA
MURIEL E. POSTON,
Skidmore College, Saratoga Springs, NY
JAMES REICHMAN,
University of California, Santa Barbara
MARC T. TESSIER-LAVIGNE,
Genentech, Inc., San Francisco, CA
JAMES TIEDJE,
Michigan State University, East Lansing
TERRY L. YATES,
University of New Mexico, Albuquerque
Senior Staff
FRANCES E. SHARPLES, Director
KERRY A. BRENNER, Senior Program Officer
MARILEE K. SHELTON-DAVENPORT, Senior Program Officer
EVONNE P.Y. TANG, Senior Program Officer
ROBERT T. YUAN, Senior Program Officer
ADAM P. FAGEN, Program Officer
ANN H. REID, Senior Program Officer
ANNA FARRAR, Financial Associate
ANNE F. JURKOWSKI, Senior Program Assistant
TOVA G. 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
