A. Y. Men, S. Amur, F. Goodsaid, F. W. Frueh, CDER, FDA, Silver Spring, MD
Purpose: To identify differentially regulated genes in tissues in response to drug X; to understand & interpret the gene expression data using ArrayTrack and to evaluate the impact of changing the parameters of data filtration such as P value and fold change on the biological interpretation of the data.
Methods: SPONSOR provided the experimental design, details and raw genomic data in a VGDS. Drug X, a MAP kinase inhibitor, or a control vehicle, was administrated orally 100mg/kg/d for 14 days to rats. Two separate tissue sections from the heart, liver, quadriceps and psoas muscles, were collected from all animals that survived until scheduled necropsy. Gene expression was determined using AffyXYZ chip and data was analyzed using Array Track Software with the data filtration parameters, P value and fold change. Biological interpretation of the gene expression was performed by Ingenuity.
Results: The number of differentially regulated genes decreased dramatically with decreasing P value and increasing fold changes in all the tissues examined. Significant differences were seen in the canonical pathways, including signaling and metabolic pathways, between the unfiltered and filtered gene sets.
Conclusions: This is an independent analysis of VGDS data submitted by SPONSOR. Our observations indicate that data Filtration plays an important role in interpretation of the gene expression data. Hybridization data cutoffs should include both p-value as well as fold-change.