“Upstream Analysis”: An Integrated Promoter-Pathway Analysis Approach to Causal Interpretation of Microarray Data

Microarrays

Jeannette Koschmann²  Anirban Bhar¹  Philip Stegmaier²  Alexander E. Kel²  Edgar Wingender² 

[1] Institute of Bioinformatics, University Medical Center Göttingen, D-37077 Göttingen, Germany; E-Mail:;geneXplain GmbH, D-38302 Wolfenbüttel, Germany; E-Mails:

关键词: microarray data;    gene expression signatures;    upstream analysis;    promoter analysis;    pathway analysis;   

DOI  :  10.3390/microarrays4020270

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.