Publication Details

Reference Category Journals
DOI / URL link
Title (Primary) Transcriptional signatures of regulatory and toxic responses to benzo-[a]-pyrene exposure
Author Michaelson, J.; Trump, S.; Rudzok, S.; Gräbsch, C.; Madureira, D.J.; Dautel, F.; Mai, J.; Attinger, S.; Schirmer, K.; von Bergen, M.; Lehmann, I.; Beyer, A.;
Journal BMC Genomics
Year 2011
Department CHS; IMMU; PROTEOM;
Volume 12
Language englisch;
Abstract

Background

Small molecule ligands often have multiple effects on the transcriptional program of a cell: they trigger a receptor specific response and additional, indirect responses ("side effects"). Distinguishing those responses is important for understanding side effects of drugs and for elucidating molecular mechanisms of toxic chemicals.

Results

We explored this problem by exposing cells to the environmental contaminant benzo-[a]-pyrene (B[a]P). B[a]P exposure activates the aryl hydrocarbon receptor (Ahr) and causes toxic stress resulting in transcriptional changes that are not regulated through Ahr. We sought to distinguish these two types of responses based on a time course of expression changes measured after B[a]P exposure. Using Random Forest machine learning we classified 81 primary Ahr responders and 1,308 genes regulated as side effects. Subsequent weighted clustering gave further insight into the connection between expression pattern, mode of regulation, and biological function. Finally, the accuracy of the predictions was supported through extensive experimental validation.

Conclusion

Using a combination of machine learning followed by extensive experimental validation, we have further expanded the known catalog of genes regulated by the environmentally sensitive transcription factor Ahr. More broadly, this study presents a strategy for distinguishing receptor-dependent responses and side effects based on expression time courses.

ID 11641
Persistent UFZ Identifier http://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=11641
Michaelson, J., Trump, S., Rudzok, S., Gräbsch, C., Madureira, D.J., Dautel, F., Mai, J., Attinger, S., Schirmer, K., von Bergen, M., Lehmann, I., Beyer, A. (2011):
Transcriptional signatures of regulatory and toxic responses to benzo-[a]-pyrene exposure
BMC Genomics 12 , art. 502