A comprehensive, mechanistically detailed, and executable model of the cell division cycle in Saccharomyces cerevisiae

Ulrike Münzner, Edda Klipp and Marcus Krantz ()
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Ulrike Münzner: Theoretical Biophysics
Edda Klipp: Theoretical Biophysics
Marcus Krantz: Theoretical Biophysics

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Understanding how cellular functions emerge from the underlying molecular mechanisms is a key challenge in biology. This will require computational models, whose predictive power is expected to increase with coverage and precision of formulation. Genome-scale models revolutionised the metabolic field and made the first whole-cell model possible. However, the lack of genome-scale models of signalling networks blocks the development of eukaryotic whole-cell models. Here, we present a comprehensive mechanistic model of the molecular network that controls the cell division cycle in Saccharomyces cerevisiae. We use rxncon, the reaction-contingency language, to neutralise the scalability issues preventing formulation, visualisation and simulation of signalling networks at the genome-scale. We use parameter-free modelling to validate the network and to predict genotype-to-phenotype relationships down to residue resolution. This mechanistic genome-scale model offers a new perspective on eukaryotic cell cycle control, and opens up for similar models—and eventually whole-cell models—of human cells.

Date: 2019
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DOI: 10.1038/s41467-019-08903-w

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