Advance Access publication September 12, 2008 FORUM Systems Biology and Mode of Action Based Risk Assessment

The applications of systems biology approaches have greatly increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical and pharmaceutical realm for diagnostic purposes and target identification. During this same period, the use of mode of action (MOA) for risk assessment has been increasing and there is a need for quantitative risk assessments on an ever-growing number of environmental chemicals. Genome-wide (i.e., global) measurements provide both a discovery engine for identifying MOA and an information base for subsequent evaluation of MOA when conducting a risk assessment. These genome-wide measure-ments are not chosen based on the hypothesized MOA and therefore represent an unbiased check of the comprehensiveness of an MOA. In addition, optimal design for MOA studies is critica