NETWORK MODELING FOR DRUG TOXICITY PREDICTION

摘要

A computational systems pharmacology framework consisting of statistical modeling and machine learning based on comprehensive integration of systems biology data, including drug target data, protein-protein interaction (PPI) networks, and gene ontology (GO) annotations, and reported drug side effects, can predict drug toxicity or drug adverse reactions (ADRs). Biomolecular network and gene annotation information can significantly improve the predictive accuracy of ADR of drugs under development. The use of PPI networks can increase prediction specificity, and the use of GO annotations can increase prediction sensitivity.

主权项

1. A system for determining drug toxicity, the system comprising:
a processor; and a plurality of modules comprising a database module, a network interaction module, a cross-validation module, and a toxicity module, each of the plurality of modules stored on a memory and executable by the processor configured to execute operation of the plurality of modules; wherein the database module configured is to extract a set of protein targets for known interactions of a particular drug with known side effects by tabulating drug target information from a first database and drug side effect information from a second database to form tabulated data; wherein the network interaction module is configured to expand said set of protein targets based on protein-protein network interaction information by combining the tabulated data with information from at least one of a protein-protein interaction network and/or a gene ontology database to produce an expanded set of targets; wherein the cross-validation module is configured to partition said expanded set of targets into a plurality of training sets and a testing set and is further configured to balance the plurality of training sets; and wherein the toxicity module is configured to determine if a toxicity reaction is likely based on said expanded set of targets and is further configured to output an evaluation of the likelihood of toxicity for the particular drug to be used to treat a particular condition.