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Domain-specific model selection for structural identification of the Rab5-Rab7 dynamics in endocytosis.

Tanevski J, Todorovski L, Kalaidzidis Y, Džeroski S - BMC Syst Biol (2015)

Bottom Line: Furthermore, taking into account the complexity of the model does not lead to better model selection.However, the use of domain-specific criteria results in a remarkable improvement over the other two model selection criteria.We also find that some of the model structures discarded as implausible in previous studies lead to the expected Rab5-Rab7 switch behavior.

View Article: PubMed Central - PubMed

Affiliation: Jožef Stefan Institute, Jamova cesta 39, Ljubljana, 1000, Slovenia. jovan.tanevski@ijs.si.

ABSTRACT

Background: Given its recent rapid development and the central role that modeling plays in the discipline, systems biology clearly needs methods for automated modeling of dynamical systems. Process-based modeling focuses on explanatory models of dynamical systems; it constructs such models from measured time-course data and formalized modeling knowledge. In this paper, we apply process-based modeling to the practically relevant task of modeling the Rab5-Rab7 conversion switch in endocytosis. The task is difficult due to the limited observability of the system variables and the noisy measurements, which pose serious challenges to the process of model selection. To address these issues, we propose a domain-specific model selection criteria that take into account knowledge about the necessary properties of the simulated model behavior.

Results: In a series of modeling experiments, we compare the results of process-based modeling obtained with different model selection criteria. The first is the standard maximum likelihood criterion based solely on least-squares model error. The second one is a parsimony-based criterion that also takes into account model complexity. We also introduce three domain-specific criteria based on domain expert expectations about the simulated behavior of an endocytosis model. According to the first criterion, 90 of the candidate models are indistinguishable. Furthermore, taking into account the complexity of the model does not lead to better model selection. However, the use of domain-specific criteria results in a remarkable improvement over the other two model selection criteria.

Conclusions: We demonstrate the applicability of process-based modeling to the task of modeling the Rab5-Rab7 dynamics in endocytosis. Our experiments show that the domain-specific criteria outperform the standard domain-independent criteria for model selection. We also find that some of the model structures discarded as implausible in previous studies lead to the expected Rab5-Rab7 switch behavior.

No MeSH data available.


The size of the error-profile plateau (black line) and the average ranks of the structures belonging to the COT (green line), IP (yellow line) and NOBS (red line) group obtained using the criterion ERX. The plot is obtained by varying the values of the α trade-off parameter in the range [0,1] with an increment of 0.1
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Fig9: The size of the error-profile plateau (black line) and the average ranks of the structures belonging to the COT (green line), IP (yellow line) and NOBS (red line) group obtained using the criterion ERX. The plot is obtained by varying the values of the α trade-off parameter in the range [0,1] with an increment of 0.1

Mentions: Combining the two domain-dependent criteria brings further improvements. Figure 9 shows the influence of α on the plateau size and the distribution of the ranks of the plausible model structures in the plateau using the ERX criterion. We observe a smooth saddle like shape of the plateau size as a function of α. The smallest plateau size is obtained for α=0.5. The size of this plateau is 33, reducing the percentage of candidate models in the plateau down to 26 %. Additional file 1: Figure S5 provides details on the results of the modeling experiment using the ERX criterion with α=0.5. There are no structures shown to not achieve bistable behavior in the plateau for values of alpha larger than 0.3 and smaller than 1.0. In comparison to using the EX criterion, the use of the combined ERX criterion leads to a slightly smaller number of models that have been shown to reproduce bistable behavior, slightly tighter range of error values and improved overall quality of the models regarding their fit to the data and the dynamic behavior of the components of the system. In the smallest plateau, out of the 33 models, 10 have structures belonging to the COT group, 7 to the IP group and none to the NOBS group. The range of errors has a mean equal to 0.47, a median of 0.44 and a standard deviation of 0.27. Using the combined criterion, no models in the plateau produce unsatisfactory behavior.Fig. 9


Domain-specific model selection for structural identification of the Rab5-Rab7 dynamics in endocytosis.

Tanevski J, Todorovski L, Kalaidzidis Y, Džeroski S - BMC Syst Biol (2015)

The size of the error-profile plateau (black line) and the average ranks of the structures belonging to the COT (green line), IP (yellow line) and NOBS (red line) group obtained using the criterion ERX. The plot is obtained by varying the values of the α trade-off parameter in the range [0,1] with an increment of 0.1
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482292&req=5

Fig9: The size of the error-profile plateau (black line) and the average ranks of the structures belonging to the COT (green line), IP (yellow line) and NOBS (red line) group obtained using the criterion ERX. The plot is obtained by varying the values of the α trade-off parameter in the range [0,1] with an increment of 0.1
Mentions: Combining the two domain-dependent criteria brings further improvements. Figure 9 shows the influence of α on the plateau size and the distribution of the ranks of the plausible model structures in the plateau using the ERX criterion. We observe a smooth saddle like shape of the plateau size as a function of α. The smallest plateau size is obtained for α=0.5. The size of this plateau is 33, reducing the percentage of candidate models in the plateau down to 26 %. Additional file 1: Figure S5 provides details on the results of the modeling experiment using the ERX criterion with α=0.5. There are no structures shown to not achieve bistable behavior in the plateau for values of alpha larger than 0.3 and smaller than 1.0. In comparison to using the EX criterion, the use of the combined ERX criterion leads to a slightly smaller number of models that have been shown to reproduce bistable behavior, slightly tighter range of error values and improved overall quality of the models regarding their fit to the data and the dynamic behavior of the components of the system. In the smallest plateau, out of the 33 models, 10 have structures belonging to the COT group, 7 to the IP group and none to the NOBS group. The range of errors has a mean equal to 0.47, a median of 0.44 and a standard deviation of 0.27. Using the combined criterion, no models in the plateau produce unsatisfactory behavior.Fig. 9

Bottom Line: Furthermore, taking into account the complexity of the model does not lead to better model selection.However, the use of domain-specific criteria results in a remarkable improvement over the other two model selection criteria.We also find that some of the model structures discarded as implausible in previous studies lead to the expected Rab5-Rab7 switch behavior.

View Article: PubMed Central - PubMed

Affiliation: Jožef Stefan Institute, Jamova cesta 39, Ljubljana, 1000, Slovenia. jovan.tanevski@ijs.si.

ABSTRACT

Background: Given its recent rapid development and the central role that modeling plays in the discipline, systems biology clearly needs methods for automated modeling of dynamical systems. Process-based modeling focuses on explanatory models of dynamical systems; it constructs such models from measured time-course data and formalized modeling knowledge. In this paper, we apply process-based modeling to the practically relevant task of modeling the Rab5-Rab7 conversion switch in endocytosis. The task is difficult due to the limited observability of the system variables and the noisy measurements, which pose serious challenges to the process of model selection. To address these issues, we propose a domain-specific model selection criteria that take into account knowledge about the necessary properties of the simulated model behavior.

Results: In a series of modeling experiments, we compare the results of process-based modeling obtained with different model selection criteria. The first is the standard maximum likelihood criterion based solely on least-squares model error. The second one is a parsimony-based criterion that also takes into account model complexity. We also introduce three domain-specific criteria based on domain expert expectations about the simulated behavior of an endocytosis model. According to the first criterion, 90 of the candidate models are indistinguishable. Furthermore, taking into account the complexity of the model does not lead to better model selection. However, the use of domain-specific criteria results in a remarkable improvement over the other two model selection criteria.

Conclusions: We demonstrate the applicability of process-based modeling to the task of modeling the Rab5-Rab7 dynamics in endocytosis. Our experiments show that the domain-specific criteria outperform the standard domain-independent criteria for model selection. We also find that some of the model structures discarded as implausible in previous studies lead to the expected Rab5-Rab7 switch behavior.

No MeSH data available.