Abstract: Systems and methods are provided for assessing perturbation of a target biological tissue caused by exposure to an agent. A set of scores indicative of a perturbation of the target biological tissue is determined based on a set of contrast data and a computational causal network model of xenobiotic metabolism in the target biological tissue and a surrogate biological tissue. The contrast data includes differences between activity measures of measurable nodes obtained from the surrogate biological tissue while exposed to the agent, and while exposed to a control. To determine the set of scores, a set of values is computed that indicates a perturbation of the surrogate biological tissue caused by the agent. A correlation is identified between the set of values for the backbone nodes obtained from the surrogate biological tissue and the set of scores that is indicative of a perturbation of the target biological tissue.