Computational disease modeling - fact or fiction?
BACKGROUND
Biomedical research is changing due to the rapid accumulation of experimental data at an unprecedented scale, revealing increasing degrees of complexity of biological processes. Life Sciences are facing a transition from a descriptive to a mechanistic approach that reveals principles of cells, cellular networks, organs, and their interactions across several spatial and temporal scales. There are two conceptual traditions in biological computational-modeling. The bottom-up approach emphasizes complex intracellular molecular models and is well represented within the systems biology community. On the other hand, the physics-inspired top-down modeling strategy identifies and selects features of (presumably) essential relevance to the phenomena of interest and combines available data in models of modest complexity.


RESULTS
The workshop, "ESF Exploratory Workshop on Computational disease Modeling", examined the challenges that computational modeling faces in contributing to the understanding and treatment of complex multi-factorial diseases. Participants at the meeting agreed on two general conclusions. First, we identified the critical importance of developing analytical tools for dealing with model and parameter uncertainty. Second, the development of predictive hierarchical models spanning several scales beyond intracellular molecular networks was identified as a major objective. This contrasts with the current focus within the systems biology community on complex molecular modeling.


CONCLUSIONS
During the workshop it became obvious that diverse scientific modeling cultures (from computational neuroscience, theory, data-driven machine-learning approaches, agent-based modeling, network modeling and stochastic-molecular simulations) would benefit from intense cross-talk on shared theoretical issues in order to make progress on clinically relevant problems.
Tegnér
Jesper N
JN
Computational Medicine group, Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden. jesper.tegner@ki.se
Compte
Albert
A
Auffray
Charles
C
An
Gary
G
Cedersund
Gunnar
G
Clermont
Gilles
G
Gutkin
Boris
B
Oltvai
Zoltán N
ZN
Stephan
Klaas Enno
KE
Thomas
Randy
R
Villoslada
Pablo
P
D001695:Biology / Q000379:methods*; D019295:Computational Biology; D003198:Computer Simulation; D004194:Disease; D006801:Humans; D008954:Models, Biological; D035501:Uncertainty