Natural computation meta-heuristics for the in silico optimization of microbial strains.

Natural computation meta-heuristics for the in silico optimization of microbial strains.
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DOI:
10.1186/1471-2105-9-499
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发表时间:
2008-11-27
期刊:
影响因子:
3
通讯作者:
Rocha, Isabel
Rocha, Isabel
中科院分区:
生物学4区
文献类型:
--
作者:
Rocha, Miguel;Maia, Paulo;Mendes, Rui;Pinto, Jose P.;Ferreira, Eugenio C.;Nielsen, Jens;Patil, Kiran Raosaheb;Rocha, Isabel

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One of the greatest challenges in Metabolic Engineering is to develop quantitative models and algorithms to identify a set of genetic manipulations that will result in a microbial strain with a desirable metabolic phenotype which typically means having a high yield/productivity. This challenge is not only due to the inherent complexity of the metabolic and regulatory networks, but also to the lack of appropriate modelling and optimization tools. To this end, Evolutionary Algorithms (EAs) have been proposed for in silico metabolic engineering, for example, to identify sets of gene deletions towards maximization of a desired physiological objective function. In this approach, each mutant strain is evaluated by resorting to the simulation of its phenotype using the Flux-Balance Analysis (FBA) approach, together with the premise that microorganisms have maximized their growth along natural evolution. This work reports on improved EAs, as well as novel Simulated Annealing (SA) algorithms to address the task of in silico metabolic engineering. Both approaches use a variable size set-based representation, thereby allowing the automatic finding of the best number of gene deletions necessary for achieving a given productivity goal. The work presents extensive computational experiments, involving four case studies that consider the production of succinic and lactic acid as the targets, by using S. cerevisiae and E. coli as model organisms. The proposed algorithms are able to reach optimal/near-optimal solutions regarding the production of the desired compounds and presenting low variability among the several runs. The results show that the proposed SA and EA both perform well in the optimization task. A comparison between them is favourable to the SA in terms of consistency in obtaining optimal solutions and faster convergence. In both cases, the use of variable size representations allows the automatic discovery of the approximate number of gene deletions, without compromising the optimality of the solutions.
DOI: 10.1186/1471-2105-6-308
发表时间: 2005-12-23
期刊: BMC BIOINFORMATICS
影响因子: 3
作者:
Patil, KR;Rocha, I;Förster, J;Nielsen, J
通讯作者: Nielsen, J
DOI: 10.1101/gr.234503
发表时间: 2003-02-01
期刊: GENOME RESEARCH
影响因子: 7
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通讯作者: Nielsen, J
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发表时间: 2006-09-01
期刊: NATURE GENETICS
影响因子: 30.8
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DOI: 10.1186/gb-2003-4-9-r54
发表时间: 2003
期刊: Genome biology
影响因子: 12.3
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通讯作者: Palsson BO
DOI: 10.1073/pnas.232349399
发表时间: 2002-11-12
影响因子: 11.1
作者:
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通讯作者: Church, GM