A framework for direct metabolic flux estimation

A. Rantanen, Juha Rousu, E. Pitkänen, Hannu Maaheimo, T. Mielikäinen, E. Ukkonen

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsScientific

Abstract

We present FluxDirect, a novel computational framework for metabolic flux estimation from incomplete isotopomer data. In FluxDirect isotopomer measurements are first propagated in the metabolic network to obtain new constraints to the isotopomer distributions of metabolites in the network. The efficient propagation is facilitated by a fragment flow analysis of a metabolic network [1]. The method can utilize any measurement information produced by common (tandem) MS- and NMR-techniques [3]. After the propagation step the basic linear stoichiometric equation system bounding the fluxes is augmented with linear measurement constraints derived from the propagated isotopomer information. If the rank of the augmented linear equation system is full, the fluxes can be easily solved. If the rank of an equation system is less than full we can output upper and lower bounds for the fluxes. The general stability of an augmented equation system can be investigated by computing the condition number of the system. Unlike in most existing methods for flux estimation, techniques of nonlinear optimization are not required. Thus FluxDirect escapes the danger of convergence to local optima. Fragment flow analysis techniques introduced for efficient propagation of isotopomer measurement data also facilitate the experimental planning of isotopomer tracer experiments. As the development of measurement techniques for internal metabolites can be tedious, it is worthwhile to look for a small set of metabolites giving adequate flux information. We have shown that such small sets can be found for FluxDirect by applying computational set cover methods [2]. The flux estimation framework is empirically tested with a model of central carbon metabolism of S. cerevisiae.
Original languageEnglish
Title of host publicationInternational Specialised Symposium on Yeasts ISSY25
Subtitle of host publicationSystems Biology of Yeasts - from Models to Applications
Place of PublicationEspoo
PublisherVTT Technical Research Centre of Finland
Pages117
ISBN (Electronic)951-38-6308-5
ISBN (Print)951-38-6307-7
Publication statusPublished - 2006
EventInternational Specialised Symposium on Yeasts, ISSY 25 - Espoo, Finland
Duration: 18 Jun 200621 Jun 2006

Publication series

NameVTT Symposium
PublisherVTT
Number242
ISSN (Print)0357-9387
ISSN (Electronic)1455-0873

Conference

ConferenceInternational Specialised Symposium on Yeasts, ISSY 25
Abbreviated titleISSY 25
CountryFinland
CityEspoo
Period18/06/0621/06/06

Fingerprint

Fluxes
Metabolites
Linear equations
Metabolism
Nuclear magnetic resonance
Planning
Carbon
Experiments
Metabolic Networks and Pathways

Cite this

Rantanen, A., Rousu, J., Pitkänen, E., Maaheimo, H., Mielikäinen, T., & Ukkonen, E. (2006). A framework for direct metabolic flux estimation. In International Specialised Symposium on Yeasts ISSY25: Systems Biology of Yeasts - from Models to Applications (pp. 117). [P62] Espoo: VTT Technical Research Centre of Finland. VTT Symposium, No. 242
Rantanen, A. ; Rousu, Juha ; Pitkänen, E. ; Maaheimo, Hannu ; Mielikäinen, T. ; Ukkonen, E. / A framework for direct metabolic flux estimation. International Specialised Symposium on Yeasts ISSY25: Systems Biology of Yeasts - from Models to Applications. Espoo : VTT Technical Research Centre of Finland, 2006. pp. 117 (VTT Symposium; No. 242).
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Rantanen, A, Rousu, J, Pitkänen, E, Maaheimo, H, Mielikäinen, T & Ukkonen, E 2006, A framework for direct metabolic flux estimation. in International Specialised Symposium on Yeasts ISSY25: Systems Biology of Yeasts - from Models to Applications., P62, VTT Technical Research Centre of Finland, Espoo, VTT Symposium, no. 242, pp. 117, International Specialised Symposium on Yeasts, ISSY 25 , Espoo, Finland, 18/06/06.

A framework for direct metabolic flux estimation. / Rantanen, A.; Rousu, Juha; Pitkänen, E.; Maaheimo, Hannu; Mielikäinen, T.; Ukkonen, E.

International Specialised Symposium on Yeasts ISSY25: Systems Biology of Yeasts - from Models to Applications. Espoo : VTT Technical Research Centre of Finland, 2006. p. 117 P62 (VTT Symposium; No. 242).

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsScientific

TY - CHAP

T1 - A framework for direct metabolic flux estimation

AU - Rantanen, A.

AU - Rousu, Juha

AU - Pitkänen, E.

AU - Maaheimo, Hannu

AU - Mielikäinen, T.

AU - Ukkonen, E.

PY - 2006

Y1 - 2006

N2 - We present FluxDirect, a novel computational framework for metabolic flux estimation from incomplete isotopomer data. In FluxDirect isotopomer measurements are first propagated in the metabolic network to obtain new constraints to the isotopomer distributions of metabolites in the network. The efficient propagation is facilitated by a fragment flow analysis of a metabolic network [1]. The method can utilize any measurement information produced by common (tandem) MS- and NMR-techniques [3]. After the propagation step the basic linear stoichiometric equation system bounding the fluxes is augmented with linear measurement constraints derived from the propagated isotopomer information. If the rank of the augmented linear equation system is full, the fluxes can be easily solved. If the rank of an equation system is less than full we can output upper and lower bounds for the fluxes. The general stability of an augmented equation system can be investigated by computing the condition number of the system. Unlike in most existing methods for flux estimation, techniques of nonlinear optimization are not required. Thus FluxDirect escapes the danger of convergence to local optima. Fragment flow analysis techniques introduced for efficient propagation of isotopomer measurement data also facilitate the experimental planning of isotopomer tracer experiments. As the development of measurement techniques for internal metabolites can be tedious, it is worthwhile to look for a small set of metabolites giving adequate flux information. We have shown that such small sets can be found for FluxDirect by applying computational set cover methods [2]. The flux estimation framework is empirically tested with a model of central carbon metabolism of S. cerevisiae.

AB - We present FluxDirect, a novel computational framework for metabolic flux estimation from incomplete isotopomer data. In FluxDirect isotopomer measurements are first propagated in the metabolic network to obtain new constraints to the isotopomer distributions of metabolites in the network. The efficient propagation is facilitated by a fragment flow analysis of a metabolic network [1]. The method can utilize any measurement information produced by common (tandem) MS- and NMR-techniques [3]. After the propagation step the basic linear stoichiometric equation system bounding the fluxes is augmented with linear measurement constraints derived from the propagated isotopomer information. If the rank of the augmented linear equation system is full, the fluxes can be easily solved. If the rank of an equation system is less than full we can output upper and lower bounds for the fluxes. The general stability of an augmented equation system can be investigated by computing the condition number of the system. Unlike in most existing methods for flux estimation, techniques of nonlinear optimization are not required. Thus FluxDirect escapes the danger of convergence to local optima. Fragment flow analysis techniques introduced for efficient propagation of isotopomer measurement data also facilitate the experimental planning of isotopomer tracer experiments. As the development of measurement techniques for internal metabolites can be tedious, it is worthwhile to look for a small set of metabolites giving adequate flux information. We have shown that such small sets can be found for FluxDirect by applying computational set cover methods [2]. The flux estimation framework is empirically tested with a model of central carbon metabolism of S. cerevisiae.

M3 - Conference abstract in proceedings

SN - 951-38-6307-7

T3 - VTT Symposium

SP - 117

BT - International Specialised Symposium on Yeasts ISSY25

PB - VTT Technical Research Centre of Finland

CY - Espoo

ER -

Rantanen A, Rousu J, Pitkänen E, Maaheimo H, Mielikäinen T, Ukkonen E. A framework for direct metabolic flux estimation. In International Specialised Symposium on Yeasts ISSY25: Systems Biology of Yeasts - from Models to Applications. Espoo: VTT Technical Research Centre of Finland. 2006. p. 117. P62. (VTT Symposium; No. 242).