A data-driven, mathematical model of mammalian cell cycle regulation

Michael C. Weis, Jayant Avva, James W. Jacobberger Sree N Sreenath

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Few of >150 published cell cycle modeling efforts use significant levels of data for tuning and validation. This reflects the difficultly to generate correlated quantitative data, and it points out a critical uncertainty in modeling efforts. To develop a data-driven model of cell cycle regulation, we used contiguous, dynamic measurements over two time scales (minutes and hours) calculated from static multiparametric cytometry data. The approach provided expression profiles of cyclin A2, cyclin B1, and phospho-S10-histone H3. The model was built by integrating and modifying two previously published models such that the model outputs for cyclins A and B fit cyclin expression measurements and the activation of B cyclin/Cdk1 coincided with phosphorylation of histone H3. The model depends on Cdh1-regulated cyclin degradation during G1, regulation of B cyclin/Cdk1 activity by cyclin A/Cdk via Wee1, and transcriptional control of the mitotic cyclins that reflects some of the current literature. We introduced autocatalytic transcription of E2F, E2F regulated transcription of cyclin B, Cdc20/Cdh1 mediated E2F degradation, enhanced transcription of mitotic cyclins during late S/early G2 phase, and the sustained synthesis of cyclin B during mitosis. These features produced a model with good correlation between state variable output and real measurements. Since the method of data generation is extensible, this model can be continually modified based on new correlated, quantitative data.

Original languageEnglish (US)
Article numbere97130
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 13 2014
Externally publishedYes

Fingerprint

Cyclin B
cyclins
Cyclins
cell cycle
Cell Cycle
Theoretical Models
mathematical models
Cells
Mathematical models
Cyclin A
Transcription
Histones
Cyclin A2
S 10
Cyclin B1
G2 Phase
Mitosis
transcription (genetics)
Degradation
Uncertainty

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Weis, M. C., Avva, J., & Jacobberger Sree N Sreenath, J. W. (2014). A data-driven, mathematical model of mammalian cell cycle regulation. PLoS One, 9(5), [e97130]. https://doi.org/10.1371/journal.pone.0097130

A data-driven, mathematical model of mammalian cell cycle regulation. / Weis, Michael C.; Avva, Jayant; Jacobberger Sree N Sreenath, James W.

In: PLoS One, Vol. 9, No. 5, e97130, 13.05.2014.

Research output: Contribution to journalArticle

Weis, MC, Avva, J & Jacobberger Sree N Sreenath, JW 2014, 'A data-driven, mathematical model of mammalian cell cycle regulation', PLoS One, vol. 9, no. 5, e97130. https://doi.org/10.1371/journal.pone.0097130
Weis, Michael C. ; Avva, Jayant ; Jacobberger Sree N Sreenath, James W. / A data-driven, mathematical model of mammalian cell cycle regulation. In: PLoS One. 2014 ; Vol. 9, No. 5.
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