Bridging in vivo and in vitro data from Japanese Toxicogenomics Project using network analyses

Abstract

Since experiments involving animal models are labor and time intensive, there is an attempt to replace these measurements on animal models with in vitro assays which has higher acceptance in the population concerning ethical issues. In this work, we explore to what extend animal models can be replaced by in vitro assays in the context of a toxicogenomics study. The data from the Japanese Toxicogenomics Project are gene expression profiles measured by microarrays from both in vitro and animal samples. We apply a comprehensive genomic association network analysis in order to study the comparative behavior of the genomic networks for the in vivo vs. in vitro data. The genomic networks are computed based on association scores of gene-gene pairs using a partial least squares modeling of gene expression values adjusted for sacrifice time and dosage. We apply permutation based statistical tests to compare the connectivity of a given gene, as well as a class of genes in the two networks which may be affected by a given drug. The goal is to identify parts of these networks including key genes that are not significantly altered for in vivo vs. in vitro samples for the majority of the drugs.