Computing knock out strategies in metabolic networks

Given a metabolic network in terms of its metabolites and reactions, our goal is to efficiently compute the minimal knock out sets of reactions required to block a given behaviour. We describe an algorithm which improves the computation of these knock out sets when the elementary modes (minimal functional subsystems) of the network are given. We also describe an algorithm which computes both the knock out sets and the elementary modes containing the blocked reactions directly from the description of the network and whose worst-case computational complexity is better than the algorithms currently in use for these problems. Computational results are included.Comment: 12 page

Quantificação de caulinita em latossolo por difração de raios-X.

bitstream/item/31910/1/CPATU-BP39.pd

Computing the shortest elementary flux modes in genome-scale metabolic networks

This article is available open access through the publisher’s website through the link below. Copyright @ The Author 2009.Motivation: Elementary flux modes (EFMs) represent a key concept to analyze metabolic networks from a pathway-oriented perspective. In spite of considerable work in this field, the computation of the full set of elementary flux modes in large-scale metabolic networks still constitutes a challenging issue due to its underlying combinatorial complexity. Results: In this article, we illustrate that the full set of EFMs can be enumerated in increasing order of number of reactions via integer linear programming. In this light, we present a novel procedure to efficiently determine the K-shortest EFMs in large-scale metabolic networks. Our method was applied to find the K-shortest EFMs that produce lysine in the genome-scale metabolic networks of Escherichia coli and Corynebacterium glutamicum. A detailed analysis of the biological significance of the K-shortest EFMs was conducted, finding that glucose catabolism, ammonium assimilation, lysine anabolism and cofactor balancing were correctly predicted. The work presented here represents an important step forward in the analysis and computation of EFMs for large-scale metabolic networks, where traditional methods fail for networks of even moderate size. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online (http://bioinformatics.oxfordjournals.org/cgi/content/full/btp564/DC1).Fundação Calouste Gulbenkian, Fundação para a Ciência e a Tecnologia (FCT) and Siemens SA Portugal

Optical spectra obtained from amorphous films of rubrene: Evidence for predominance of twisted isomer

In order to investigate the optical properties of rubrene we study the vibronic progression of the first absorption band (lowest \pi -> \pi^* transition). We analyze the dielectric function of rubrene in solution and thin films using the displaced harmonic oscillator model and derive all relevant parameters of the vibronic progression. The findings are supplemented by density functional calculations using B3LYP hybrid functionals. Our theoretical results for the molecule in two different conformations, i.e. with a twisted or planar tetracene backbone, are in very good agreement with the experimental data obtained for rubrene in solution and thin films. Moreover, a simulation based on the monomer spectrum and the calculated transition energies of the two conformations indicates that the thin film spectrum of rubrene is dominated by the twisted isomer.Comment: 7 pages, 6 figure

An optimization model for metabolic pathways

This article is available open access through the publisher’s website through the link below. Copyright @ The Author 2009.Motivation: Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online (http://bioinformatics.oxfordjournals.org/cgi/content/full/btp441/DC1)

Computing paths and cycles in biological interaction graphs

<p>Abstract</p> <p>Background</p> <p>Interaction graphs (signed directed graphs) provide an important qualitative modeling approach for Systems Biology. They enable the analysis of causal relationships in cellular networks and can even be useful for predicting qualitative aspects of systems dynamics. Fundamental issues in the analysis of interaction graphs are the enumeration of paths and cycles (feedback loops) and the calculation of shortest positive/negative paths. These computational problems have been discussed only to a minor extent in the context of Systems Biology and in particular the shortest signed paths problem requires algorithmic developments.</p> <p>Results</p> <p>We first review algorithms for the enumeration of paths and cycles and show that these algorithms are superior to a recently proposed enumeration approach based on elementary-modes computation. The main part of this work deals with the computation of shortest positive/negative paths, an NP-complete problem for which only very few algorithms are described in the literature. We propose extensions and several new algorithm variants for computing either exact results or approximations. Benchmarks with various concrete biological networks show that exact results can sometimes be obtained in networks with several hundred nodes. A class of even larger graphs can still be treated exactly by a new algorithm combining exhaustive and simple search strategies. For graphs, where the computation of exact solutions becomes time-consuming or infeasible, we devised an approximative algorithm with polynomial complexity. Strikingly, in realistic networks (where a comparison with exact results was possible) this algorithm delivered results that are very close or equal to the exact values. This phenomenon can probably be attributed to the particular topology of cellular signaling and regulatory networks which contain a relatively low number of negative feedback loops.</p> <p>Conclusion</p> <p>The calculation of shortest positive/negative paths and cycles in interaction graphs is an important method for network analysis in Systems Biology. This contribution draws the attention of the community to this important computational problem and provides a number of new algorithms, partially specifically tailored for biological interaction graphs. All algorithms have been implemented in the <it>CellNetAnalyzer </it>framework which can be downloaded for academic use at <url>http://www.mpi-magdeburg.mpg.de/projects/cna/cna.html</url>.</p

Caracterização morfológica e física de solos adensados dos tabuleiros sertanejos do Estado de Pernambuco.

Este estudo teve como objetivo a caracterização morfológica e física de solos com horizontes subsuperficiais adensados, visando identificar e diagnosticar os possíveis processos envolvidos na formação destes horizontes. Foram selecionados três perfis de solos representativos, ao longo de uma topossequência, localizadas nos tabuleiros sertanejos, município de Petrolina, Zona Semi-Árida do Estado de Pernambuco. Os solos foram caracterizados morfologicamente e, nas amostras coletadas por horizonte, foi efetuada a caracterização física. A homegeneidade das características morfológicas e físicas indica que os três perfis estudados são derivados do mesmo material de origem, provenientes da intensa mistura tanto dos sedimentos que caracterizam a grande área pedimentar da região quanto de alguns produtos do embasamento cristalino subjacente. O adensamento subsuperficial deve-se a processos pedogenéticos como eluviação/iluviação de argila, que atua reduzindo a porosidade; bem como por processos de plintitização e dispersão de argila, influenciados por ciclos alternados de umedecimento e secagem.bitstream/item/66030/1/BPD-134-Solos-Tabuleiros-Sertanejos-Com-correcoes.pd

A Taxonomy of Causality-Based Biological Properties

We formally characterize a set of causality-based properties of metabolic networks. This set of properties aims at making precise several notions on the production of metabolites, which are familiar in the biologists' terminology. From a theoretical point of view, biochemical reactions are abstractly represented as causal implications and the produced metabolites as causal consequences of the implication representing the corresponding reaction. The fact that a reactant is produced is represented by means of the chain of reactions that have made it exist. Such representation abstracts away from quantities, stoichiometric and thermodynamic parameters and constitutes the basis for the characterization of our properties. Moreover, we propose an effective method for verifying our properties based on an abstract model of system dynamics. This consists of a new abstract semantics for the system seen as a concurrent network and expressed using the Chemical Ground Form calculus. We illustrate an application of this framework to a portion of a real metabolic pathway