LTMap: a web server for assessing the potential liver toxicity by genome-wide transcriptional expression data

Abstract

Toxicogenomics (TGx) has played a significant role in mechanistic research related with hepatotoxicity as well as liver toxicity prediction. Currently, several large-scale preclinical TGx data sets were made freely accessible to the public, such as Open TG-GATEs. With the availability of a sufficient amount of microarray data, it is important to integrate this information to provide new insights into the risk assessment of potential drug-induced liver toxicity. Here we developed a web server for evaluating the potential liver toxicity based on genome-wide transcriptomics data, namely LTMap. In LTMap, researchers could compare signatures of query compounds against a pregenerated signature database of 20 123 Affymetrix arrays associated with about 170 compounds retrieved from the largest public toxicogenomics data set Open TG-GATEs. Results from this comparison may lead to the unexpected discovery of similar toxicological responses between chemicals. We validated our computational approach for similarity comparison using three example drugs. Our successful applications of LTMap in these case studies demonstrated its utility in revealing the connection of chemicals according to similar toxicological behaviors. Furthermore, a user-friendly web interface is provided by LTMap to browse and search toxicogenomics data (http://tcm.zju.edu.cn/ltmap).

Keywords: Toxicogenomics; hepatotoxicity; risk assessment; web server.