title: A network perspective on metabolic inconsistency.
abstract: BACKGROUND
  Integrating gene expression profiles and metabolic pathways under different experimental conditions is essential for understanding the coherence of these two layers of cellular organization. The network character of metabolic systems can be instrumental in developing concepts of agreement between expression data and pathways. A network-driven interpretation of gene expression data has the potential of suggesting novel classifiers for pathological cellular states and of contributing to a general theoretical understanding of gene regulation.
  
  
  RESULTS
  Here, we analyze the coherence of gene expression patterns and a reconstruction of human metabolism, using consistency scores obtained from network and constraint-based analysis methods. We find a surprisingly strong correlation between the two measures, demonstrating that a substantial part of inconsistencies between metabolic processes and gene expression can be understood from a network perspective alone. Prompted by this finding, we investigate the topological context of the individual biochemical reactions responsible for the observed inconsistencies. On this basis, we are able to separate the differential contributions that bear physiological information about the system, from the unspecific contributions that unravel gaps in the metabolic reconstruction. We demonstrate the biological potential of our network-driven approach by analyzing transcriptome profiles of aldosterone producing adenomas that have been obtained from a cohort of Primary Aldosteronism patients. We unravel systematics in the data that could not have been resolved by conventional microarray data analysis. In particular, we discover two distinct metabolic states in the adenoma expression patterns.
  
  
  CONCLUSIONS
  The methodology presented here can help understand metabolic inconsistencies from a network perspective. It thus serves as a mediator between the topology of metabolic systems and their dynamical function. Finally, we demonstrate how physiologically relevant insights into the structure and dynamics of metabolic networks can be obtained using this novel approach.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. niko.sonnenschein@gmail.com
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Sonnenschein
authors.forename: José Felipe
authors.initials: JF
authors.lastname: Golib Dzib
authors.forename: Annick
authors.initials: A
authors.lastname: Lesne
authors.forename: Sebastian
authors.initials: S
authors.lastname: Eilebrecht
authors.forename: Sheerazed
authors.initials: S
authors.lastname: Boulkroun
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.forename: Arndt
authors.initials: A
authors.lastname: Benecke
authors.forename: Marc-Thorsten
authors.initials: MT
authors.lastname: Hütt
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000272:Adipates / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis; D006801:Humans; D053858:Metabolic Networks and Pathways; D011392:Proline / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D059467:Transcriptome
chemical_list: D000272:Adipates; D011758:Pyrroles; C015485:delta-1-pyrroline-5-carboxylate; D000450:Aldosterone; D011392:Proline; C001918:alpha-ketoadipic acid