Reconstructing metabolic flux vectors from extreme pathways: defining the α-spectrum

Wiback, Sharon J.; Mahadevan, Radhakrishnan; Palsson, Bernhard Ø.

doi:10.1016/s0022-5193(03)00168-1

Cited by 83 publications

(71 citation statements)

References 31 publications

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“…All possible steady-state flux solutions can then be represented as nonnegative linear combinations of these extreme pathways. Further analysis using a number of tools, such as SVD and α-spectrum analyses, is performed, see Price et al (2003a);Wiback et al (2003) for details.…”

Section: Linear Programming Solutionmentioning

confidence: 99%

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Bayesian flux balance analysis applied to a skeletal muscle metabolic model

Heino

Tunyan

Calvetti

et al. 2007

Journal of Theoretical Biology

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In this article, the steady state condition for the multi-compartment models for cellular metabolism is considered. The problem is to estimate the reaction and transport fluxes, as well as the concentrations in venous blood when the stoichiometry and bound constraints for the fluxes and the concentrations are given. The problem has been addressed previously by a number of authors, and optimization based approaches as well as extreme pathway analysis have been proposed. These approaches are briefly discussed here. The main emphasis of this work is a Bayesian statistical approach to the flux balance analysis (FBA). We show how the bound constraints and optimality conditions such as maximizing the oxidative phosphorylation flux can be incorporated into the model in the Bayesian framework by proper construction of the prior densities. We propose an effective Markov Chain Monte Carlo (MCMC) scheme to explore the posterior densities, and compare the results with those obtained via the previously studied Linear Programming (LP) approach. The proposed methodology, which is applied here to a two-compartment model for skeletal muscle metabolism, can be extended to more complex models.

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Section: Linear Programming Solutionmentioning

confidence: 99%

“…Since the number of extreme pathways can be very large for large-scale metabolic network systems (Papin et al, 2002a(Papin et al, , 2003, a set of improved tools was developed to solve these problems (Barrett et al, 2006;Price et al, 2003b;Wiback et al, 2003).…”

Section: Linear Programming Solutionmentioning

confidence: 99%

Bayesian flux balance analysis applied to a skeletal muscle metabolic model

Heino

Tunyan

Calvetti

et al. 2007

Journal of Theoretical Biology

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“…Notice also that in general a given v cannot be uniquely decomposed into an activity pattern w, but a space of valid solutions exists (Wiback, 2003). 1 This is also true for the rest of generating sets that will be introduced in subsequent sections.…”

Section: Different Concepts Of Pathwaysmentioning

confidence: 98%

“…Two approaches are usually followed: chose one pattern based on a reasonably assumption (Poolman, 2004;Schwartz, 2006), or deal with the whole space of possible patterns. The second approach relies on the so-called α-spectrum, the ranges of possible activities for each pathway (Wiback, 2003).…”

Section: Introductionmentioning

confidence: 99%

Interval and Possibilistic Methods for Constraint-Based Metabolic Models

Estrada¹

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In the following site the reader will find updated information regarding this thesis. This includes corrections and clarifications, connections with future works, publications, software and tools, etc.http://science.ensilicio.com/Thesis/Thesis.html AgradecimientosLa tesis doctoral es un viaje emocionante, exigente y no exento de riesgos. Por suerte, resulta mucho mejor, más sencillo y más divertido, cuando uno tiene una lista de agradecimientos tan extensa como la mía.Estoy en deuda con mi director, Jesús Picó, por darme la oportunidad de trabajar en lo que me gusta, por descubrirme un tema fascinante y por dirigirme sabiamente en el desarrollo de esta tesis. También con mis supervisores durante mis estancias en el extranjero, Georges Bastin y Vassily Hatzimanikatis, porque me permitieron aprender de su trabajo, conocer sus instituciones y explorar dos países.Le agradezco a Antonio Sala que se acercase un buen día con una propuesta para colaborar (haciendo así fructíferas las reuniones en la biblioteca); y a Marta Tortajada que fuese mi coautora en varias ocasiones y que sea una de las personas cuyas ideas más me han ayudado. He aprendido mil cosas de otras personas -profesores, compañeros, colegas, revisores, etc.-y a todos les estoy agradecido.A los compañeros que encontré camino al doctorado les agradezco, sobretodo, que hicieran mi trabajo divertido. Agradezco cada café y cada conversación. Mención especial merecen mis principales compañeros de viaje, Pepe y Sergio, por su camaradería en el trabajo y en la vida.Es probable que sin el apoyo de otras personas no hubiese terminado esta tesis... y es seguro que de haberlo hecho sería irrelevante. A mi familia -Juan, María, Juan-les agradezco que sean mi refugio, porque la existencia de ese «lugar» me permite el lujo de ser temerario. A mis amigos en la vecindad les agradezco su interés por las victorias de cada día; y tanto a ellos como al resto, les doy las gracias por creer incondicionalmente que lo que hacía, fuese lo que fuese, era digno de admirar. Mi deuda es especial con Lucia porque ella fue la recompensa en los días de trabajo y sacrificio.Por último, y por encima de todo, quiero agradecer a mis padres todo lo que hicieron y el modo preciso en que lo hicieron. Sé que eso excede el ámbito de esta tesis, pero este párrafo es un buen lugar para mostrarles mi gratitud. Gracias. AbstractThis thesis is devoted to the study and application of constraint-based metabolic models. The objective was to find simple ways to handle the difficulties that arise in practice due to uncertainty (knowledge is incomplete, there is a lack of measurable variables, and those available are imprecise). With this purpose, tools have been developed to model, analyse, estimate and predict the metabolic behaviour of cells.The document is structured in three parts. First, related literature is revised and summarised. This results in a unified perspective of several methodologies that use constraint-based representations of the cell metabolism. Three outstanding methods are discussed i...

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“…One such attempt is the concept of the α spectrum [145], which involves a linear optimization to determine how the extreme pathways (EPs) (a systemically independent subset of EMs) contribute to a given steady-state flux distribution. This algorithm allows the determination of maximum and minimum possible weightings for each extreme pathway.…”

Section: Network-based Pathway Analysis: Elementary Modes (Ems)mentioning

confidence: 99%

Chemometric Approaches for Systems Biology

Fortuny¹

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The present Ph.D. thesis is devoted to study, develop and apply approaches commonly used in chemometrics to the emerging field of systems biology. Existing procedures and new methods are applied to solve research and industrial questions in different multidisciplinary teams. The methodologies developed in this document will enrich the plethora of procedures employed within omic sciences to understand biological organisms and will improve processes in biotechnological industries integrating biological knowledge at different levels and exploiting the software packages derived from the thesis.This dissertation is structured in four parts. The first block describes the framework in which the contributions presented here are based. The objectives of the two research projects related to this thesis are highlighted and the specific topics addressed in this document via conference presentations and research articles are introduced. A comprehensive description of omic sciences and their relationships within the systems biology paradigm is given in this part, jointly with a review of the most applied multivariate methods in chemometrics, on which the novel approaches proposed here are founded.The second part addresses many problems of data understanding within metabolomics, fluxomics, proteomics and genomics. Different alternatives are proposed in this block to understand flux data in steady state conditions. Some are based on applications of multivariate methods previously applied in other chemometrics areas. Others are novel approaches based on a bilinear decomposition using elemental metabolic pathways, from which a GNU licensed toolbox is made freely available for the scientific community. As well, a framework for metabolic data understanding is proposed for non-steady state data, using the same bilinear decomposition proposed for steady state data, but modelling the dynamics of the experiments using novel two and three-way data analysis procedures. Also, the relationships between different omic levels are assessed in this part integrating different sources of information of plant viruses in data fusion models. Finally, an example of interaction between organisms, oranges and fungi, is studied via multivariate image analysis techniques, with future application in food industries.v The third block of this thesis is a thoroughly study of different missing data problems related to chemometrics, systems biology and industrial bioprocesses. In the theoretical chapters of this part, new algorithms to obtain multivariate exploratory and regression models in the presence of missing data are proposed, which serve also as preprocessing steps of any other methodology used by practitioners. Regarding applications, this block explores the reconstruction of networks in omic sciences when missing and faulty measurements appear in databases, and how calibration models between near infrared instruments can be transferred, avoiding costs and time-consuming full recalibrations in bioindustries and research laboratories. Finally,...

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Reconstructing metabolic flux vectors from extreme pathways: defining the α-spectrum

Cited by 83 publications

References 31 publications

Bayesian flux balance analysis applied to a skeletal muscle metabolic model

Bayesian flux balance analysis applied to a skeletal muscle metabolic model

Interval and Possibilistic Methods for Constraint-Based Metabolic Models

Chemometric Approaches for Systems Biology

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