Metabolic network segmentation: A probabilistic graphical modeling approach to identify the sites and sequential order of metabolic regulation from non-targeted metabolomics data
Open access
Date
2017-06-09Type
- Journal Article
Abstract
In recent years, the number of large-scale metabolomics studies on various cellular processes in different organisms has increased drastically. However, it remains a major challenge to perform a systematic identification of mechanistic regulatory events that mediate the observed changes in metabolite levels, due to complex interdependencies within metabolic networks. We present the metabolic network segmentation (MNS) algorithm, a probabilistic graphical modeling approach that enables genome-scale, automated prediction of regulated metabolic reactions from differential or serial metabolomics data. The algorithm sections the metabolic network into modules of metabolites with consistent changes. Metabolic reactions that connect different modules are the most likely sites of metabolic regulation. In contrast to most state-of-the-art methods, the MNS algorithm is independent of arbitrary pathway definitions, and its probabilistic nature facilitates assessments of noisy and incomplete measurements. With serial (i.e., time-resolved) data, the MNS algorithm also indicates the sequential order of metabolic regulation. We demonstrated the power and flexibility of the MNS algorithm with three, realistic case studies with bacterial and human cells. Thus, this approach enables the identification of mechanistic regulatory events from large-scale metabolomics data, and contributes to the understanding of metabolic processes and their interplay with cellular signaling and regulation processes. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000190463Publication status
publishedExternal links
Journal / series
PLoS Computational BiologyVolume
Pages / Article No.
Publisher
Public Library of ScienceOrganisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
03713 - Sauer, Uwe / Sauer, Uwe
03984 - Claassen, Manfred (ehemalig) / Claassen, Manfred (former)
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