Dataset Information

Optimization of Allelic Combinations Controlling Parameters of a Peach Quality Model.

ABSTRACT: Process-based models are effective tools to predict the phenotype of an individual in different growing conditions. Combined with a quantitative trait locus (QTL) mapping approach, it is then possible to predict the behavior of individuals with any combinations of alleles. However the number of simulations to explore the realm of possibilities may become infinite. Therefore, the use of an efficient optimization algorithm to intelligently explore the search space becomes imperative. The optimization algorithm has to solve a multi-objective problem, since the phenotypes of interest are usually a complex of traits, to identify the individuals with best tradeoffs between those traits. In this study we proposed to unroll such a combined approach in the case of peach fruit quality described through three targeted traits, using a process-based model with seven parameters controlled by QTL. We compared a current approach based on the optimization of the values of the parameters with a more evolved way to proceed which consists in the direct optimization of the alleles controlling the parameters. The optimization algorithm has been adapted to deal with both continuous and combinatorial problems. We compared the spaces of parameters obtained with different tactics and the phenotype of the individuals resulting from random simulations and optimization in these spaces. The use of a genetic model enabled the restriction of the dimension of the parameter space toward more feasible combinations of parameter values, reproducing relationships between parameters as observed in a real progeny. The results of this study demonstrated the potential of such an approach to refine the solutions toward more realistic ideotypes. Perspectives of improvement are discussed.

SUBMITTER: Quilot-Turion B

PROVIDER: S-EPMC5167719 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Optimization of Allelic Combinations Controlling Parameters of a Peach Quality Model.

Quilot-Turion Bénédicte B Génard Michel M Valsesia Pierre P Memmah Mohamed-Mahmoud MM

Frontiers in plant science 20161220

Process-based models are effective tools to predict the phenotype of an individual in different growing conditions. Combined with a quantitative trait locus (QTL) mapping approach, it is then possible to predict the behavior of individuals with any combinations of alleles. However the number of simulations to explore the realm of possibilities may become infinite. Therefore, the use of an efficient optimization algorithm to intelligently explore the search space becomes imperative. The optimizat ...[more]

PMID: 28066450

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Project description:BACKGROUND:Numerous oncology combination therapies involving modulators of the cancer immune cycle are being developed, yet quantitative simulation models predictive of outcome are lacking. We here present a model-based analysis of tumor size dynamics and immune markers, which integrates experimental data from multiple studies and provides a validated simulation framework predictive of biomarkers and anti-tumor response rates, for untested dosing sequences and schedules of combined radiation (RT) and anti PD-(L)1 therapies. METHODS:A quantitative systems pharmacology model, which includes key elements of the cancer immunity cycle and the tumor microenvironment, tumor growth, as well as dose-exposure-target modulation features, was developed to reproduce experimental data of CT26 tumor size dynamics upon administration of RT and/or a pharmacological IO treatment such as an anti-PD-L1 agent. Variability in individual tumor size dynamics was taken into account using a mixed-effects model at the level of tumor-infiltrating T cell influx. RESULTS:The model allowed for a detailed quantitative understanding of the synergistic kinetic effects underlying immune cell interactions as linked to tumor size modulation, under these treatments. The model showed that the ability of T cells to infiltrate tumor tissue is a primary determinant of variability in individual tumor size dynamics and tumor response. The model was further used as an in silico evaluation tool to quantitatively predict, prospectively, untested treatment combination schedules and sequences. We demonstrate that anti-PD-L1 administration prior to, or concurrently with RT reveal further synergistic effects, which, according to the model, may materialize due to more favorable dynamics between RT-induced immuno-modulation and reduced immuno-suppression of T cells through anti-PD-L1. CONCLUSIONS:This study provides quantitative mechanistic explanations of the links between RT and anti-tumor immune responses, and describes how optimized combinations and schedules of immunomodulation and radiation may tip the immune balance in favor of the host, sufficiently to lead to tumor shrinkage or rejection.

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Optimization of Allelic Combinations Controlling Parameters of a Peach Quality Model.

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Optimization of Allelic Combinations Controlling Parameters of a Peach Quality Model.

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