Multi-scale stochastic organization-oriented coarse-graining exemplified on the human mitotic checkpoint

Research output: Contribution to journalArticle

Authors

  • Richard Henze
  • Chunyan Mu
  • Mate Puljiz
  • Nishanthan Kamaleson
  • Jan Huwald
  • John Haslegrave
  • Pietro Speroni di Fenizio
  • Bashar Ibrahim
  • Peter Dittrich

Colleges, School and Institutes

External organisations

  • Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena, Jena, Germany.
  • School of Computing, Teesside University, Teesside, UK.
  • Faculty of Electrical Engineering and Computing, University of Zagreb, Zagreb, Croatia.
  • Warwick Mathematics Institute, University of Warwick
  • Chair of Bioinformatics, Matthias Schleiden Institute, Friedrich Schiller University of Jena, Jena, Germany.

Abstract

The complexity of biological models makes methods for their analysis and understanding highly desirable. Here, we demonstrate the orchestration of various novel coarse-graining methods by applying them to the mitotic spindle assembly checkpoint. We begin with a detailed fine-grained spatial model in which individual molecules are simulated moving and reacting in a three-dimensional space. A sequence of manual and automatic coarse-grainings finally leads to the coarsest deterministic and stochastic models containing only four molecular species and four states for each kinetochore, respectively. We are able to relate each more coarse-grained level to a finer one, which allows us to relate model parameters between coarse-grainings and which provides a more precise meaning for the elements of the more abstract models. Furthermore, we discuss how organizational coarse-graining can be applied to spatial dynamics by showing spatial organizations during mitotic checkpoint inactivation. We demonstrate how these models lead to insights if the model has different "meaningful" behaviors that differ in the set of (molecular) species. We conclude that understanding, modeling and analyzing complex bio-molecular systems can greatly benefit from a set of coarse-graining methods that, ideally, can be automatically applied and that allow the different levels of abstraction to be related.

Details

Original languageEnglish
Article number3902
Number of pages17
JournalScientific Reports
Volume9
Issue number1
Publication statusPublished - 7 Mar 2019