A data integration approach for cell cycle analysis oriented to model simulation in systems biology.
BACKGROUND
The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies.


METHODS
In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process.


CONCLUSIONS
This integrated system is freely available in order to support systems biology research on the cell cycle and it aims to become a useful resource for collecting all the information related to actual and future models of this network. The flexibility of the database allows the addition of mathematical data which are used for simulating the behavior of the cell cycle components in the different models. The resource deals with two relevant problems in systems biology: data integration and mathematical simulation of a crucial biological process related to cancer, such as the cell cycle. In this way the resource is useful both to retrieve information about cell cycle model components and to analyze their dynamical properties. The Cell Cycle Database can be used to find system-level properties, such as stable steady states and oscillations, by coupling structure and dynamical information about models.
Istituto di Tecnologie Biomediche - Consiglio Nazionale delle Ricerche, via F,lli Cervi 93, Segrate (Milano), Italy. roberta.alfieri@itb.cnr.it
Roberta
R
Alfieri
Ivan
I
Merelli
Ettore
E
Mosca
Luciano
L
Milanesi
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016208:Databases, Factual; D008322:Mammals; D008954:Models, Biological; D049490:Systems Biology / Q000379:methods*; D015003:Yeasts / Q000166:cytology
D018797:Cell Cycle Proteins