Sysmetab, 13C metabolic flux analysis with Scilab

Sysmetab, 13C metabolic flux analysis with Scilab

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Introduction

Sysmetab is a software solving stationary and non-stationary MFA-CLE (Metabolic Flux Analysis from Carbon Labeling Experiments). MFA-CLE aims to determine asymptotic reaction rates in a metabolic network from MS (Mass Spectrometry) and/or NMR (Nuclear Magnetic Resonance) measurements. The theory of associated direct and inverse problems can be found in the following papers :

Wiechert, W. and Wurzel, M. (2001). Metabolic isotopomer labeling systems: Part I: global dynamic behavior. Mathematical Biosciences, 169(2), 173 – 205.

Wiechert, W. and Isermann N. (2003), Metabolic isotopomer labeling systems. Part II: structural flux identifiability analysis Mathematical Biosciences, 183, 175-214.

Wiechert, W., Möllney, M., Isermann, N., Wurzel, M., and de Graaf, A. A. (1999). Bidirectional reaction steps in metabolic networks: III. Explicit solution and analysis of isotopomer labeling systems. Biotechnol. Bioeng., 66(2), 69-85.

Implementation

Metabolic network input data description, carbon atom transition map (in reactions) and experimental measurements are given in a plain text XML file conforming to the Flux Markup Language (http://www.13cflux.net/fluxml) format developped for the 13CFlux2 software ({http://www.13cflux.net/13cflux2}). FTBL format input files are also supported and automatically converted to the FML format, as the previous version of the 13CFlux software was designed for. The Sysmetab software parses this file to generate automatically a specific program to the network under consideration in the Scilab language.

The FluxML language is fully described in chapter 11 of Michael Weitzel's thesis, which can be found at the following addresses :

http://citeseerx.ist.psu.edu

http://elweitzel.de/files/diss.pdf

Innovative aspects

1. Adjoint approach

To compute the gradient of the residual sum of squares, Sysmetab uses the adjoint approach. The mathematical and practical details are summarized in the following paper "Metabolic Flux Analysis in Isotope Labeling Experiments using the Adjoint Approach" IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2016 (DOI 10.1109/TCBB.2016.2544299, to appear) arXiv:1601.04588 [q-bio.MN]

2. Code generation with XSLT

Another innovative aspect of the software, besides the adjoint approach, remain in the choice of the generating code technique: from the original FML file, only XSL transformations (http://www.w3.org/TR/xslt) are used to generate the Scilab program. These transformations are described in XSL stylesheets, written in another XML dialect. XSL is very different from the typical programming languages commonly used today because it is a declarative (as opposed to imperative) language. An important aspect of this choice is that the XSL stylesheets are very explicit, human readable, and easy to debug and maintain. The generation of the program is done in several steps, the last being devoted to the XML program description transformation into the actual Scilab program. This last transformation can be easily adapted to other script languages such as Matlab (http:/www.mathworks.com) or Julia (http://julialang.org).

Linearized statistics or Monte-Carlo simulations can be used to make confidence intervals on estimated fluxes available. When the latter method is used, Scilab allows parallel execution of the optimization algorithm on a multi-core architecture. After execution of the generated program, the complete results of the optimization are collected in a plain text XML file conforming to the Forward Simulation Markup Language (http://www.13cflux.net/fwdsim) developed for the 13CFlux2 software. This file can be easily processed with XSL transformations in order to convert it to other file formats.

Documentation

The documentation (work in progress) is available at the following address

http://forge.scilab.org/index.php/p/sysmetab/doc/

Licensing

Sysmetab was developed at the Applied Mathematics Laboratory (LMAC, EA 2222) and at the Process Engineering Laboratory (TIMR, EA 4297) of UTC (Université de Technologie de Compiègne), Compiègne, FRANCE

The software has been licenced under the CECILL license until version 5.0. You may obtain a copy of this license at the following address:

http://opensource.org/licenses/CECILL-2.1

Since version 5.1 Sysmetab is released under the GPL License Version 3. You may obtain a copy of this license at the following address:

https://www.gnu.org/licenses/gpl-3.0.en.html

If you publish results obtained with Sysmetab, please cite the original arXiv report (see above).

Third party software

Sysmetab uses the Scilab implementation of CFSQP Copyright (c) 1993-1998 by Craig T. Lawrence, Jian L. Zhou, and Andre L. Tits. The CFSQP routines may only be used for research and development, unless it has been agreed otherwise with the authors in writing. Distribution and licensing of FSQP is handled by Ms. Alla McCoy (acmccoy@umd.edu) at the University of Maryland's Office of Technology Commercialization.

Software Authors

Stéphane MOTTELET, EA4297 TIMR, Université de Technologie de Compiègne, Compiègne, France, stephane.mottelet@utc.fr

Gil GAULLIER, EA2222 LMAC, Université de Technologie de Compiègne, Compiègne, France, gil.gaullier@gmail.com

Georges SADAKA, UMR7352 LAMFA, Université de Picardie Jules Verne, Amiens, France, georges.sadaka@u-picardie.fr

Acknowledgments

Part of the developments was performed in partnership with the SAS PIVERT, within the frame of the French Institute for the Energy Transition (Institut pour la Transition Energtique - ITE) P.I.V.E.R.T. (www.institut-pivert.com) selected as an Investment for the Future (”Investissements d’Avenir”). This work was supported, as part of the Investments for the Future, by the French Government under the reference ANR-001-01

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updated Wed Jul 13 21:03:56 CEST 2016

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