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2016 ; 3
(ä): 6
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A Strategy for Functional Interpretation of Metabolomic Time Series Data in
Context of Metabolic Network Information
#MMPMID27014700
Nägele T
; Fürtauer L
; Nagler M
; Weiszmann J
; Weckwerth W
Front Mol Biosci
2016[]; 3
(ä): 6
PMID27014700
show ga
The functional connection of experimental metabolic time series data with
biochemical network information is an important, yet complex, issue in systems
biology. Frequently, experimental analysis of diurnal, circadian, or
developmental dynamics of metabolism results in a comprehensive and
multidimensional data matrix comprising information about metabolite
concentrations, protein levels, and/or enzyme activities. While, irrespective of
the type of organism, the experimental high-throughput analysis of the
transcriptome, proteome, and metabolome has become a common part of many systems
biological studies, functional data integration in a biochemical and
physiological context is still challenging. Here, an approach is presented which
addresses the functional connection of experimental time series data with
biochemical network information which can be inferred, for example, from a
metabolic network reconstruction. Based on a time-continuous and
variance-weighted regression analysis of experimental data, metabolic functions,
i.e., first-order derivatives of metabolite concentrations, were related to
time-dependent changes in other biochemically relevant metabolic functions, i.e.,
second-order derivatives of metabolite concentrations. This finally revealed time
points of perturbed dependencies in metabolic functions indicating a modified
biochemical interaction. The approach was validated using previously published
experimental data on a diurnal time course of metabolite levels, enzyme
activities, and metabolic flux simulations. To support and ease the presented
approach of functional time series analysis, a graphical user interface including
a test data set and a manual is provided which can be run within the numerical
software environment Matlab®.