"Upstream Analysis": An Integrated Promoter-Pathway Analysis Approach to Causal Interpretation of Microarray Data.
A strategy is presented that allows a causal analysis of co-expressed genes, which may be subject to common regulatory influences. A state-of-the-art promoter analysis for potential transcription factor (TF) binding sites in combination with a knowledge-based analysis of the upstream pathway that control the activity of these TFs is shown to lead to hypothetical master regulators. This strategy was implemented as a workflow in a comprehensive bioinformatic software platform. We applied this workflow to gene sets that were identified by a novel triclustering algorithm in naphthalene-induced gene expression signatures of murine liver and lung tissue. As a result, tissue-specific master regulators were identified that are known to be linked with tumorigenic and apoptotic processes. To our knowledge, this is the first time that genes of expression triclusters were used to identify upstream regulators.
Xplain GmbH, D-38302 Wolfenbüttel, Germany. jeannette.koschmann@genexplain.com.
Jeannette
J
Koschmann
Institute of Bioinformatics, University Medical Center Göttingen, D-37077 Göttingen, Germany. anirban.bhar@bioinf.med.uni-goettingen.de.
Anirban
A
Bhar
Xplain GmbH, D-38302 Wolfenbüttel, Germany. philip.stegmaier@genexplain.com.
Philip
P
Stegmaier
Xplain GmbH, D-38302 Wolfenbüttel, Germany. alexander.kel@genexplain.com.
Alexander E
AE
Kel
Xplain GmbH, D-38302 Wolfenbüttel, Germany. anirban.bhar@bioinf.med.uni-goettingen.de.|Institute of Bioinformatics, University Medical Center Göttingen, D-37077 Göttingen, Germany. anirban.bhar@bioinf.med.uni-goettingen.de.
Edgar
E
Wingender
gene expression signatures; microarray data; pathway analysis; promoter analysis; upstream analysis