Molecular toxicology modeling
OwnerDonna L. Mendrick, Mark W. Porter +3inventors
InventorsDonna L. Mendrick, Mark W. Porter, Kory R. Johnson, Arthur L. Castle, Michael R. Elashoff
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Abstract
The present invention is based on the elucidation of the global changes in gene expression and the identification of toxicity markers in tissues or cells exposed to a known toxin. The genes may be used as toxicity markers in drug screening and toxicity assays. The invention includes a database of genes characterized by toxin-induced differential expression that is designed for use with microarrays and other solid-phase probes.
Claims54
A method of predicting at least one toxic effect of a compound, comprising:
- (a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 1-3;
- wherein differential expression of the genes in Tables 1-3 is indicative of at least one toxic effect.
A method of predicting the progression of a toxic effect of a compound, comprising:
- (a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 1-3;
- wherein differential expression of the genes in Tables 1-3 is indicative of toxicity progression.
A method of predicting the hepatotoxicity of a compound, comprising:
- (a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 1-3;
- wherein differential expression of the genes in Tables 1-3 is indicative of hepatotoxicity.
A method of identifying an agent that modulates the onset or progression of a toxic response, comprising:
- (a) exposing a cell to the agent and a known toxin;
- and
- (b) detecting the expression level of two or more genes from Tables 1-3;
- wherein differential expression of the genes in Tables 1-3 is indicative of toxicity.
A method of predicting the cellular pathways that a compound modulates in a cell, comprising:
- (a) detecting the level of expression in a tissue or cell sample exposed to the compound of two or more genes from Tables 1-3;
- wherein differential expression of the genes in Tables 1-3 is associated the modulation of at least one cellular pathway.
A set of at least two probes, wherein each of the probes comprises a sequence that specifically hybridizes to a gene in Tables 1-3.
A solid support comprising at least two probes, wherein each of the probes comprises a sequence that specifically hybridizes to a gene in Tables 1-3.
A computer system comprising:
- (a) a database containing information identifying the expression level in a tissue or cell sample exposed to a hepatotoxin of a set of genes comprising at least two genes in Tables 1-3;
- and
- (b) a user interface to view the information.
50 A method of claim 48, wherein the hybridization assay is selected from the group consisting of Northern blot, dot or slot blot, nuclease protection and microarray assays.
A method of identifying an agent that modulates at least one activity of a protein encoded by a gene in Tables 1-3 comprising:
- (a) exposing the protein to the agent;
- and
- (b) assaying at least one activity of said protein.
Dependencies are inferred from the claim text.