Fachbereich Informatik - Aktuell
Disputation Michael Römer
am Mittwoch, 24. Mai 2017 in Raum A104, Sand 1, EG.
Prediction and visualization of the carcinogenic potential of chemicals with short-term omics assays
Berichterstatter 1: Prof. Andreas Zell
Berichterstatter 2: Prof. Michael Schwarz
Drug candidates that induce or promote cancer formation must be identified and eliminated during the preclinical phase of drug development to minimize the risk of adverse, carcinogenic effects in patients. Genotoxic carcinogens can be identified with short-term assays. In contrast, the lifetime rodent cancer bioassay that is used to identify nongenotoxic carcinogenic substances, requires a high number of test animals and takes up to five years for completion. In addition, the lifetime rodent cancer bioassay does not provide sufficient data to evaluate the human risk if carcinogenic effects are observed in rodents. This can result in discontinuation of the development of the drug candidate or a black label warning on the drug packaging. The application of high-throughput omics methods such as transcriptomics or proteomics in toxicological studies is a promising approach for the development of short-term alternatives to the lifetime rodent cancer bioassay. However, these omics methods are difficult to use for life sciences researchers and few specialized visualization tools exist for toxicogenomics data. Furthermore, most existing studies used only a single omics platform to determine the molecular effects of carcinogens.
We introduced new approaches that integrate multiple omics platforms for the identification of nongenotoxic carcinogens and presented analysis and visualization tools that were specifically developed for toxicogenomics data. We performed a series of experiments to demonstrate that our multi-omics approach improves the prediction performance compared to single-omics approaches. To facilitate the access to our analysis and visualization tools, we implemented two web platforms, the ZBIT Bioinformatics Toolbox and MARCARviz. These web platforms enable toxicologists to gain new insights into the mechanisms of nongenotoxic tumor promotion. Furthermore, we demonstrated that our multi-omics approach can provide the basis of new short-term alternatives to the lifetime rodent cancer bioassay.