SYSTEMS AND METHODS FOR EVALUATING PERTURBATION OF XENOBIOTIC METABOLISM

摘要

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.

主权项

1. A computerized method for assessing perturbation of a target biological tissue of mammalian origin caused by exposure to an agent, comprising:
determining a set of scores that is indicative of a perturbation of the target biological tissue based on:
(a) a computational causal network model of xenobiotic metabolism in the target biological tissue and a surrogate biological tissue, the model comprising measurable nodes and backbone nodes connected by edges, the backbone nodes and measurable nodes each representing a biological activity related to xenobiotic metabolism, the edges representing causal relationships between connected nodes, wherein an activity value of a respective backbone node is determined by activity measures of the measurable nodes that are connected to the respective backbone node; and(b) a set of contrast data comprising differences between the activity measures of the measurable nodes obtained from a sample of the surrogate biological tissue that is exposed to the agent, and the activity measures of the measurable nodes obtained from a sample of the surrogate biological tissue that is exposed to a control, wherein the determining the set of scores comprises:
(i) computing, at a first processor, a set of values for the backbone nodes using the set of contrast data; wherein:the set of values for the backbone nodes indicates a perturbation of the surrogate biological tissue caused by the agent; anda correlation 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 is identified.