Predicting Chemical Carcinogenesis: Problem Representation Governs Model Performance
Speaker: Douglas W. Bristol, National Institute of Environmental Health Sciences
When: 2003-07-08 11:00:00
Venue: 78-420
Host: Marcus Gallagher
Abstract:Predictive models for chemical carcinogenesis are needed to help
manage the safe use of over 100,000 chemical substances worldwide,
as well as to guide decisions made during development of new
chemicals. Three Predictive-Toxicology Challenges (PTC) have
stimulated the development of such models over the past decade. Each
was an open, collaborative experiment that attracted
cross-disciplinary participants and resources. Learning sets were
compiled from standardized chemical bioassays for carcinogenesis
conducted in rodents by the U.S. National Toxicology Program. ROC
convex-hull analysis was applied to evaluate the predictive
performance of 54 individual models, within and across the three PTC
experiments. Evaluation of model comprehensibility or the coherence
of individual models with domain knowledge requires further
development effort. Additionally, the three PTC experiments and
individual models utilized three different paradigms for
representing the nature of the problem. When classified according to
whether a model was developed using only chemical-structure
attributes, only biological-system attributes, or a mix of chemical
and biological attributes, it is clear that mixed-attribute models,
which reflect interactions between chemical and biological features,
clearly outperform those based on only biological or chemical
attributes. Thus, the interaction paradigm offers opportunities to
develop predictive models with high accuracy and broad coverage,
but, more importantly, to discover features and relationships that
govern mechanistic pathways for chemical carcinogenesis and provide
insight into effects, such as those that transcend species, gender,
and route of exposure.
Biography:Douglas W. Bristol bristol@niehs.nih.gov, Toxicology Operations
Branch, Environmental Toxicology Program, Division of Intramural
Research, National Institute of Environmental Health Sciences,
Research Triangle Park, NC 27709, USA
Type: ITEE Seminar
Contact:Marcus Gallagher, seminar host (marcusg@itee.uq.edu.au)
or Guido Governatori (ITEE seminar co-ordinator)
(guido@itee.uq.edu.au)