An elastic network model to identify characteristic stress response genes

Computational Biology and Chemistry
Sebastian SchneckenerAndreas Schuppert

Abstract

Exposing eukaryotic cells to a toxic compound and subsequent gene expression profiling may allow the prediction of selected toxic effects based on changes in gene expression. This objective is complicated by the observation that compounds with different modes of toxicity cause similar changes in gene expression and that a global stress response affects many genes. We developed an elastic network model of global stress response with nodes representing genes which are connected by edges of graded coexpression. The expression of only few genes have to be known to model the global stress response of all but a few atypical responder genes. Those required genes and the atypical response genes are shown to be good biomarker for tox predictions. In total, 138 experiments and 13 different compounds were used to train models for different toxicity classes. The deduced biomarkers were shown to be biologically plausible. A neural network was trained to predict the toxic effects of compounds from profiling experiments. On a validation data set of 189 experiments with 16 different compounds the accuracy of the predictions was assessed: 14 out of 16 compounds have been classified correctly. Derivation of model based biomarkers through the ela...Continue Reading

References

Apr 1, 1981·Journal of Pharmacobio-dynamics·T KuboY Misu
May 7, 1999·Environmental Health Perspectives·R E ShackelfordR S Paules
Dec 19, 2001·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Claudia M HattingerRoeland W Dirks
Feb 2, 2002·Science·Ali H Brivanlou, James E Darnell
Apr 23, 2002·Molecular Microbiology·Pavel P Khil, R Daniel Camerini-Otero
Dec 31, 2002·Chemistry and Physics of Lipids·Benjamin F Cravatt, Aron H Lichtman
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Apr 13, 2004·Oncogene·Takao OhtsukaSam W Lee
Jul 21, 2004·Bioinformatics·Dennis Kostka, Rainer Spang
Sep 17, 2004·Nature·Nicholas M LuscombeMark Gerstein
May 14, 2005·Mutation Research·Heidrun Ellinger-ZiegelbauerHans Juergen Ahr
Jul 7, 2005·Genes & Development·Alexandre Blais, Brian David Dynlacht
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jun 27, 2008·Algorithms for Molecular Biology : AMB·Koji KadotaKentaro Shimizu
Jul 2, 2008·Nature Reviews. Genetics·Luis López-MauryJürg Bähler
Oct 23, 2008·Nucleic Acids Research·Tanya BarrettRon Edgar

❮ Previous
Next ❯

Citations

Dec 4, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jean-Louis SteimerIñaki F Troconiz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis