20 Years After Launch: 13C Metabolic Flux Analysis Becomes Visual

The first papers on ¹³C-Metabolic Flux Analysis integrating the full methodological triad of i) cultivation under well controlled conditions, ii) MS or NMR ¹³C labeling measurements, and iii) mathematical modeling of the metabolic network were published 20 years ago [1]. Since then, ¹³C-MFA experienced a fairly dynamic development and became an indispensable tool for directing flux to wanted targets [2]. The workflow of ¹³C-MFA is highly organism and experiment specific and, thus, requires painstaking attention [3]. Apart from the composition of various experimental and analytical tasks, a major hurdle in generating high-quality flux maps is orchestration of several modeling and computational steps in an iterative and interactive workflow [4].

We here present the first fully graphical tool suite for ¹³C-MFA based on the Omix visualization software [5] and featuring the high-performance simulator 13CFLUX2 [6]. Scientists are provided with an integrated visual modeling environment for network construction, atom transition specification, measurement modeling, input substrate composition, experimental design, or flux map presentation just to mention a few of the implemented tools. Almost 30 Omix plugins have been implemented for this purpose. Several advanced graphical workflows and ergonomic user interfaces support major domain-specific modeling and proofreading tasks. With these features, the novel suite is a productivity-boosting tool. Remarkably, part of the flux analysis workflow already found its way to Agilentâ??s VistaFlux, the first commercial software for qualitative MFA [7].

References:
[1] Marx A, et al. (1996) Determination of the fluxes in central metabolism of Corynebacterium glutamicum. BiotechnBioeng49:111-129.
[2] Niedenführ S, Wiechert W, Nöh K (2015) How to measure metabolic fluxes: a taxonomic guide for ¹³C fluxomics. CurrOpBiotechnol 34:82-90.
[3] Buescher JM, et al. (2015) A roadmap for interpreting ¹³C metabolite labeling patterns from cells. CurrOpBiotechn 34:189-201.
[4] Wiechert W, Niedenführ S, Nöh K (2016) A primer to ¹³C metabolic flux analysis, Wiley Encyclopedia Biotechnology, Vol. 1:97-142.
[5] Nöh K, Droste P, Wiechert W (2015) Visual workflows for ¹³C-metabolic flux analysis. Bioinformatics, 31:346-354.
[6] M. Weitzel, et al. (2013) 13CFLUX2 - High-performance software suite for ¹³C-metabolic flux analysis. Bioinformatics 29:143-145.
[7] Agilent Technologies (2016), VistaFlux Software, Santa Clara, USA 2016.