This Phase I SBIR project uses a new Quality Control microarray (QCarray) technology to generate Drug Toxicity Signatures (DTSs) for predicting liver toxicity in rat. The QCarray enables each element on every array to have a quality control (QC) score and markedly reduces a common source of error: fabrication of the cDNA microarrays. A second source of variability in arrays is genetic heterogeneity; therefore, we will benchmark the QCarray and look for DTSs using the PharmGenix Panel. The PharmGenix Panel models a heterozygous, variable genetic background in a controlled setting while reliably detecting drug toxicity. PhysioGenix will leverage archived tissues from previous PharmGenix drug studies and generate liver-specific DTSs to four different hepatotoxins. Matarray software will QC and normalize array data while principal component analysis will cluster expression patterns according to clinical chemistry, to help to determine informative DTSs. Phase II efforts will generate DTSs for toxicity to kidney and heart, and compare the liver DTSs to non-human primates. The common DTSs will be posited to be predictive biomarkers in the drug development process. Deliverables from this project will be of interest to the FDA and marketed to pharmaceutical companies for implementation into their existing drug development process.
