Multiscale Spatial Computational Systems Biology

Summary

This seminar built on the tradition of two previous Dagstuhl seminars on Formal Methods in Molecular Biology in 2009 and 2011 (Seminar 09091, Seminar 11151), but with a special focus on multiscale and spatial modeling and simulation.

Multiscale modelling goes beyond the traditional approach of modelling at just one spatial/temporal scale or organizational level. Until now most models have largely ignored locality within the cell, or cell-cell interactions. However, with the insight that spatial phenomena like localisation and crowding have a considerable influence on reaction processes and many processes cannot be understood with reference to one organisation level only (intra- or inter-cellular dynamics), the need for effective and efficient modelling and simulation approaches arises.

The challenges for computer science and mathematics include the development of suitable modelling approaches and associated tools to create coherent descriptions of biological systems by integrating several spatial and/or temporal scales, and methods for the simulation and analysis of the models.

The overall motivation for this seminar was the exploration of the most recent advances in these methods. The seminar brought together researchers working in modelling and analysis of biological systems with diverse professional backgrounds, including informaticians, mathematicians, engineers, biologists, physicians.

A distinguishing factor of the seminar was the modelling exercise - where teams explored different modelling paradigms, in order to better understand the details of the approaches, their challenges, potential applications, and their pros and cons. This activity was carried out in a collaborative and self-directed manner using the Open Space Technology approach as evidenced by a high degree of communication both within and between the teams. Eight teams were formed, and reports from five of them are included in this document. The teams were formed around the following focii:

• Small GTP-ase pathway.
• Continuous multiscale models for biological tissue.
• Simulating macromolecular crowding with particle and lattice-based methods
• Multiscale modeling of S1P metabolism, secretion and signaling
• DNA structural dynamics.
• Dictyostelium discoideum: Aggregation and Synchronisation of Amoebas in Time and Space.
• Towards a standard exchange format for spatial, multilevel multicellular models.
• Model checking for multiscale spatial biological systems.

The participants decided to take forward the activities in the future outside Dagstuhl, with the goals of carrying out collaborative research, producing scientific papers and applying for larger scale funded international research projects.