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The Karyote simulator is based
on a biomic model that accounts for the interaction of the genome,
proteome and metabolome and their interplay with intra-cellular
structural dynamics. This conceptual flow chart is the schematic
basis for Karyote. |
Karyote
: A Genomic, Proteomic, Metabolic Cell Simulator
Karyote is a quantitative model of the dynamics of a cell and its response to chemical disturbances,
gene deletion/mutation and the presence of other cells. Karyote is based on the numerical solution of a
set of reaction-transport equations underlying the kinetics of genomic, proteomic and metabolic processes
(see figure). It is integrated with a variety of experimental data types through our novel information
theory approach; the result is an automated procedure for tailoring Karyote to a given cell type and that
all predictions are accompanied by an assessment of uncertainty. Karyote also serves as a data archive
with self-consistent automated interpretation of the expanding genomic, proteomic, metabolic and other
information. Through our information theory framework, incompleteness in Karyote can be compensated for
with time series data; complex data sets can be automatically synthesized and integrated. In this way
Karyote is an end-to-end cell modeling system.
Karyote has great potential for accelerating drug discovery, optimizing treatment regimes, testing concepts
in cloning and designing microbes for biotechnical and environmental remediation activities. The information you
input to Karyote can be kept proprietary or may be released to other users. You may export models as SBML files.
You may delete your information from our files at any time. All data is regularly backed up. If it is of interest
the Karyote System can be installed at your site by special arrangement.
Reactions take place in user-designated compartments. Molecules may exchange across membranes separating
compartments. Reactions can also be introduced that involve reactants and products on both sides of a membrane
(e.g. active pumps or membrane-embedded enzymes). Multiple timescale and stiff solvers are used to account for
reactions that take place on widely ranging timescales.
Karyote is self-sustaining. The underlying physico-chemical model generates mRNA from the user-supplied DNA
nucleotide sequence using polymerization kinetics. RNA synthesis is controlled by a network of transcription
factor-mediated processes affecting RNA polymerase binding to each gene. Proteins are created using ribosome-mediated
polymerization and post-translational modification kinetic equations. Through self-assembly kinetics, enzymes and
ribosomes are assembled and control metabolic, transcription, translation and other processes. This closes one of the
feedback loops among the many that underlie living cell behavior. Reactions may be entered in great generality or can
be retrieved from a database. Tutorials and example models provide an introduction to general concepts and the practical
use of the system. Karyote can serve as an advanced research tool or as an element of an undergraduate course in cell biology.