Digital Organisms
Digital organisms are comprehensive computational models of whole organisms. We are researching ways in which to build these large computational models and have already developed several aspects of this. Presently our main focus is on creating dynamic models of whole-cell metabolism, based on ordinary differential equations.
Whole-cell metabolism models of S. cerevisiae
We have built several iterations of this. The first was carried out using lin-log kinetics (a kinetic type that requires small numbers of parameters). More recently we have been using "modular kinetics", which represent more properties of enzyme kinetics (eg saturation).
Models available:
- model with 1748 species and 1059 reactions (lin-log kinetics) from Smallbone et al. 2010, also available from BioModels database as MODEL1001200000
- model with 657 species and 282 reactions (lin-log kinetics) from Smallbone & Mendes 2013, available from BioModels database as BIOMD0000000471
- model with 657 species and 282 reactions (modular kinetics) from Smallbone & Mendes 2013, available from BioModels database as BIOMD0000000472
- model with 657 species and 282 reactions (modular kinetics) merged with the model of Pritchard & Kell, from Smallbone & Mendes 2013, available from BioModels database as BIOMD0000000473
- model with 295 species, 285 reactions (no allosteric interactions) from Stanford et al. 2013
- model with 295 species, 285 reactions (with allosteric interactions) from Stanford et al. 2013
Currently the most sophisticated model is number 4 above.
Whole-cell metabolism models of E. coli
We have also produced models for E. coli metabolism using the same procedures as for yeast.
Models available:
- model with 786 species and 399 reactions (lin-log kinetics) from Smallbone & Mendes 2013, available from BioModels database as BIOMD0000000469
- model with 786 species and 399 reactions (modular kinetics) from Smallbone & Mendes 2013, available from BioModels database as BIOMD0000000470
Currently the most sophisticated model is number 2 above.
Bibliography
- Stanford NJ, Lubitz T, Smallbone K, Klipp E, Mendes P, Liebermeister W (2013) Systematic construction of kinetic models from genome-scale metabolic networks PLoS ONE 8:e79195 [full text]
- Smallbone K, Mendes P (2013) Large-scale metabolic models: from reconstruction to differential equations. Industrial Biotechnology 9 ,179-184 [full text]
- Stanford NJ (2011) Towards a full genome-scale model of yeast metabolism. PhD Thesis, The University of Manchester UK. [full text]
- Smallbone, K, Simeonidis, E, Swainston, N, Mendes, P (2010) Towards a genome-scale kinetic model of cellular metabolism. BMC Systems Biology 4, 6 [full text]