# Difference between revisions of "Performance of objective functions and optimization procedures for parameter estimation in system biology models"

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=== Summary === | === Summary === | ||

− | + | In systems biology, relative data are a common occurrence. In ODE-based models, this is regarded by either introducing scaling parameters or data-driven normalization to bring data and simulations onto the same scale. It was shown in this article, that data-driven normalization improves optimization performance and does not aggravate non-identifiability problems compared to a scaling factor approach. Furthermore, this article reports that hybrid optimization methods which combine stochastic global and deterministic local search outperforms deterministic local gradient-based strategies. | |

=== Study outcomes === | === Study outcomes === | ||

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− | + | ==== Identifiability ==== | |

− | + | Employing data-driven normalization instead of scaling factors improved the identifiability of dynamic parameters, providing a computational example to demonstrate how this occurs. | |

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+ | ==== Convergence Speed ==== | ||

+ | As visualized in Fig. 4 and Fig. 5 of the original publication, convergence speed was consistently improved using data driven normalization compared to scaling factors. Combining the data-driven normalization with the hybrid optimization algorithm GLSDC provided the best performance results especially in high-parameter settings. | ||

=== Study design and evidence level === | === Study design and evidence level === | ||

− | + | * The provided claims are tested on 3 parameter estimation problems with varying amount of parameters. | |

− | + | * The 3 main algorithms tested were GLSDC, LevMar SE, LevMar FD with scaling factors and data normalization each. These were tested in 96 runs each. | |

− | The | + | * Although the previously best-performing method using LSQNONLIN with sensitivity equations as found in [[Lessons Learned from Quantitative Dynamical Modeling in Systems Biology]] has been mentioned, but a comparison with GLSDC was restricted to use of their implementation of the algorithm. |

− | + | * The study used Least-Squares instead of Likelihood as objective function, omitting error model fits. | |

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=== Further comments and aspects === | === Further comments and aspects === | ||

− | + | * Additionally to the performance advantages of not using scaling factors, it is also stated that the amount of overfitting is reduced. | |

− | The | + | * The notion of practical identifiability does deviates from other literature, see for example e.g. [https://doi.org/10.1093/bioinformatics/btp358 Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood] |

+ | * The objective function values in Fig. 4 and Fig. 5 are not entirely obvious to interpret, since stochastic algorithms and multi-start algorithms are analyzed. |

## Latest revision as of 13:38, 25 February 2020

## Contents

### 1 Citation

Andrea Degasperi, Dirk Fey & Boris N. Kholodenko, Performance of objective functions and optimisation procedures for parameter estimation in system biology models, 2017, Systems Biology and Applications volume 3, Article number: 20

### 2 Summary

In systems biology, relative data are a common occurrence. In ODE-based models, this is regarded by either introducing scaling parameters or data-driven normalization to bring data and simulations onto the same scale. It was shown in this article, that data-driven normalization improves optimization performance and does not aggravate non-identifiability problems compared to a scaling factor approach. Furthermore, this article reports that hybrid optimization methods which combine stochastic global and deterministic local search outperforms deterministic local gradient-based strategies.

### 3 Study outcomes

#### 3.1 Identifiability

Employing data-driven normalization instead of scaling factors improved the identifiability of dynamic parameters, providing a computational example to demonstrate how this occurs.

#### 3.2 Convergence Speed

As visualized in Fig. 4 and Fig. 5 of the original publication, convergence speed was consistently improved using data driven normalization compared to scaling factors. Combining the data-driven normalization with the hybrid optimization algorithm GLSDC provided the best performance results especially in high-parameter settings.

### 4 Study design and evidence level

- The provided claims are tested on 3 parameter estimation problems with varying amount of parameters.
- The 3 main algorithms tested were GLSDC, LevMar SE, LevMar FD with scaling factors and data normalization each. These were tested in 96 runs each.
- Although the previously best-performing method using LSQNONLIN with sensitivity equations as found in Lessons Learned from Quantitative Dynamical Modeling in Systems Biology has been mentioned, but a comparison with GLSDC was restricted to use of their implementation of the algorithm.
- The study used Least-Squares instead of Likelihood as objective function, omitting error model fits.

### 5 Further comments and aspects

- Additionally to the performance advantages of not using scaling factors, it is also stated that the amount of overfitting is reduced.
- The notion of practical identifiability does deviates from other literature, see for example e.g. Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood
- The objective function values in Fig. 4 and Fig. 5 are not entirely obvious to interpret, since stochastic algorithms and multi-start algorithms are analyzed.