Dataset Information

Grid-based computational methods for the design of constraint-based parsimonious chemical reaction networks to simulate metabolite production: GridProd.

ABSTRACT:

Background

Constraint-based metabolic flux analysis of knockout strategies is an efficient method to simulate the production of useful metabolites in microbes. Owing to the recent development of technologies for artificial DNA synthesis, it may become important in the near future to mathematically design minimum metabolic networks to simulate metabolite production.

Results

We have developed a computational method where parsimonious metabolic flux distribution is computed for designated constraints on growth and production rates which are represented by grids. When the growth rate of this obtained parsimonious metabolic network is maximized, higher production rates compared to those noted using existing methods are observed for many target metabolites. The set of reactions used in this parsimonious flux distribution consists of reactions included in the original genome scale model iAF1260. The computational experiments show that the grid size affects the obtained production rates. Under the conditions that the growth rate is maximized and the minimum cases of flux variability analysis are considered, the developed method produced more than 90% of metabolites, while the existing methods produced less than 50%. Mathematical explanations using examples are provided to demonstrate potential reasons for the ability of the proposed algorithm to identify design strategies that the existing methods could not identify.

Conclusion

We developed an efficient method for computing the design of minimum metabolic networks by using constraint-based flux balance analysis to simulate the production of useful metabolites. The source code is freely available, and is implemented in MATLAB and COBRA toolbox.

SUBMITTER: Tamura T

PROVIDER: S-EPMC6137756 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Grid-based computational methods for the design of constraint-based parsimonious chemical reaction networks to simulate metabolite production: GridProd.

Tamura Takeyuki T

BMC bioinformatics 20180914 1

<h4>Background</h4>Constraint-based metabolic flux analysis of knockout strategies is an efficient method to simulate the production of useful metabolites in microbes. Owing to the recent development of technologies for artificial DNA synthesis, it may become important in the near future to mathematically design minimum metabolic networks to simulate metabolite production.<h4>Results</h4>We have developed a computational method where parsimonious metabolic flux distribution is computed for desig ...[more]

PMID: 30217144

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Project description:Prediction problems in biomedical sciences are generally quite difficult, partially due to incomplete knowledge of how the phenomenon of interest is influenced by the variables and measurements used for prediction, as well as a lack of consensus regarding the ideal predictor(s) for specific problems. In these situations, a powerful approach to improving prediction performance is to construct ensembles that combine the outputs of many individual base predictors, which have been successful for many biomedical prediction tasks. Moreover, selecting a parsimonious ensemble can be of even greater value for biomedical sciences, where it is not only important to learn an accurate predictor, but also to interpret what novel knowledge it can provide about the target problem. Ensemble selection is a promising approach for this task because of its ability to select a collectively predictive subset, often a relatively small one, of all input base predictors. One of the most well-known algorithms for ensemble selection, CES (Caruana et al.'s Ensemble Selection), generally performs well in practice, but faces several challenges due to the difficulty of choosing the right values of its various parameters. Since the choices made for these parameters are usually ad-hoc, good performance of CES is difficult to guarantee for a variety of problems or datasets. To address these challenges with CES and other such algorithms, we propose a novel heterogeneous ensemble selection approach based on the paradigm of reinforcement learning (RL), which offers a more systematic and mathematically sound methodology for exploring the many possible combinations of base predictors that can be selected into an ensemble. We develop three RL-based strategies for constructing ensembles and analyze their results on two unbalanced computational genomics problems, namely the prediction of protein function and splice sites in eukaryotic genomes. We show that the resultant ensembles are indeed substantially more parsimonious as compared to the full set of base predictors, yet still offer almost the same classification power, especially for larger datasets. The RL ensembles also yield a better combination of parsimony and predictive performance as compared to CES.

Dataset Information

Grid-based computational methods for the design of constraint-based parsimonious chemical reaction networks to simulate metabolite production: GridProd.

Background

Results

Conclusion

Publications

Grid-based computational methods for the design of constraint-based parsimonious chemical reaction networks to simulate metabolite production: GridProd.

Similar Datasets

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