PathWave: Discovering patterns of differentially regulated enzymes in metabolic pathways

Schramm, Gunnar, Wiesberg, Stefan, Diessl, Nicolle, Kranz, Anna-Lena, Sagulenko, Vitalia, Oswald, Marcus, Reinelt, Gerhard, Westermann, Frank, Eils, Roland and Konig, Rainer (2010) PathWave: Discovering patterns of differentially regulated enzymes in metabolic pathways. Bioinformatics, 26 9: 1225-1231. doi:10.1093/bioinformatics/btq113


Author Schramm, Gunnar
Wiesberg, Stefan
Diessl, Nicolle
Kranz, Anna-Lena
Sagulenko, Vitalia
Oswald, Marcus
Reinelt, Gerhard
Westermann, Frank
Eils, Roland
Konig, Rainer
Title PathWave: Discovering patterns of differentially regulated enzymes in metabolic pathways
Journal name Bioinformatics   Check publisher's open access policy
ISSN 1367-4811
1367-4803
Publication date 2010-05-01
Sub-type Article (original research)
DOI 10.1093/bioinformatics/btq113
Volume 26
Issue 9
Start page 1225
End page 1231
Total pages 7
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Motivation: Gene expression profiling by microarrays or transcript sequencing enables observing the pathogenic function of tumors on a mesoscopic level.
Results: We investigated neuroblastoma tumors that clinically exhibit a very heterogeneous course ranging from rapid growth with fatal outcome to spontaneous regression and detected regulatory oncogenetic shifts in their metabolic networks. In contrast to common enrichment tests, we took network topology into account by applying adjusted wavelet transforms on an elaborated and new 2D grid representation of curated pathway maps from the Kyoto Enzyclopedia of Genes and Genomes. The aggressive form of the tumors showed regulatory shifts for purine and pyrimidine biosynthesis as well as folate-mediated metabolism of the one-carbon pool in respect to increased nucleotide production. We spotted an oncogentic regulatory switch in glutamate metabolism for which we provided experimental validation, being the first steps towards new possible drug therapy. The pattern recognition method we used complements normal enrichment tests to detect such functionally related regulation patterns.
Availability and Implementation: PathWave is implemented in a package for R (www.r-project.org) version 2.6.0 or higher. It is freely available from http://www.ichip.de/software/pathwave.html
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 20 Oct 2011, 10:00:20 EST by Vitaliya Sagulenko on behalf of School of Chemistry & Molecular Biosciences