350

25

Phenomics

25.5

Modeling Life

Motivations for numerically modeling living cells and organisms include the possi-

bilities of investigating the effects of environmental factors much more rapidly and

comprehensively than via actual in vivo experimentation, and precisely testing ideas

about underlying mechanisms of biological activity. The conventional approach has

been to construct a set of differential equations corresponding to all the known reac-

tions inside a cell and in the intercellular medium and solve it numerically. It meets

almost insuperable obstacles, however: not only is the system of equations, corre-

sponding to thousands of reactions, very complicated, but many of the parameters

(rate coefficients and reagent concentrations) are not reliably known.

A very different alternative approach is to emulate, rather than simulate, an organ-

ism. To this end, the cell-based virtual living organism (VLO) has been created. ¹⁶

This is a modular approach in which the exchange of information between modules

plays a key rôle. The degree of granularity is important here: the emulation needs to

be fast enough to be useful when run on a computer but accurate enough to capture the

essential features of biology. Direct simulations typically aim to model every known

biochemical reaction but apart from the fact that many of the required rate coefficients

and other relevant parameters are unknown, such simulations would generate vast

amounts of superfluous information, obscuring the important concepts. The VLO is

based on a hierarchy of the concepts of life/living, organism, organ, tissue and cell.

As in a real organism, the cell plays a key rôle and all the work is done at the cellular

level. In the VLO, cells give out jobs to other cells of other types and wait for the

job results (which may be chemicals) when they are needed.

Models of biological systems in general, and the VLO in particular, may be useful

for predicting the response of an organism to certain drugs, or the probability of

creating a tumour given certain environmental conditions, and so forth. It is perhaps

best viewed as a rapid prototyping tool, analogous to their very useful and already

widely used counterparts in mechanical engineering.

References

Ashby WR (1956) An introduction to cybernetics. Chapman and Hall, London

Bándi G, Ramsden JJ (2010) Biological programming. J Biol Phys Chem 10:5–8

Bándi G, Ramsden JJ (2011) Emulating biology: the virtual living organism. J Biol Phys Chem

11:97–106

Barglow KT, Cravatt BF (2007) Activity-based protein profiling for the functional annotation of

enzymes. Nat Methods 4:822–827

Bilder RM, Sabb FW, Cannon TD, London ED, Jentsch JD, Parker DS, Poldrack RA, Evans C,

Freimer NB (2009) Phenomics: the systematic study of phenotypes on a genome-wide scale.

Neuroscience 164:30–42

16 Bándi and Ramsden 2010, 2011.