8 research outputs found
Identifying the parametric occurrence of multiple steady states for some biological networks
We consider a problem from biological network analysis of determining regions
in a parameter space over which there are multiple steady states for positive
real values of variables and parameters. We describe multiple approaches to
address the problem using tools from Symbolic Computation. We describe how
progress was made to achieve semi-algebraic descriptions of the
multistationarity regions of parameter space, and compare symbolic results to
numerical methods. The biological networks studied are models of the
mitogen-activated protein kinases (MAPK) network which has already consumed
considerable effort using special insights into its structure of corresponding
models. Our main example is a model with 11 equations in 11 variables and 19
parameters, 3 of which are of interest for symbolic treatment. The model also
imposes positivity conditions on all variables and parameters.
We apply combinations of symbolic computation methods designed for mixed
equality/inequality systems, specifically virtual substitution, lazy real
triangularization and cylindrical algebraic decomposition, as well as a
simplification technique adapted from Gaussian elimination and graph theory. We
are able to determine multistationarity of our main example over a
2-dimensional parameter space. We also study a second MAPK model and a symbolic
grid sampling technique which can locate such regions in 3-dimensional
parameter space.Comment: 60 pages - author preprint. Accepted in the Journal of Symbolic
Computatio
Parametric Toricity of Steady State Varieties of Reaction Networks
We study real steady state varieties of the dynamics of chemical reaction
networks. The dynamics are derived using mass action kinetics with parametric
reaction rates. The models studied are not inherently parametric in nature.
Rather, our interest in parameters is motivated by parameter uncertainty, as
reaction rates are typically either measured with limited precision or
estimated. We aim at detecting toricity and shifted toricity, using a framework
that has been recently introduced and studied for the non-parametric case over
both the real and the complex numbers. While toricity requires that the variety
specifies a subgroup of the direct power of the multiplicative group of the
underlying field, shifted toricity requires only a coset. In the non-parametric
case these requirements establish real decision problems. In the presence of
parameters we must go further and derive necessary and sufficient conditions in
the parameters for toricity or shifted toricity to hold. Technically, we use
real quantifier elimination methods. Our computations on biological networks
here once more confirm shifted toricity as a relevant concept, while toricity
holds only for degenerate parameter choices.Comment: Computations available as ancillary file
Identifying the Parametric Occurrence of Multiple Steady States for some Biological Networks
We consider a problem from biological network analysis of determining regions in a parameter space over which there are multiple steady states for positive real values of variables and parameters. We describe multiple approaches to address the problem using tools from Symbolic Computation. We describe how progress was made to achieve semi-algebraic descriptions of the multistationarity regions of parameter space, and compare symbolic results to numerical methods. The biological networks studied are models of the mitogen-activated protein kinases (MAPK) network which has already consumed considerable effort using special insights into its structure of corresponding models. Our main example is a model with 11 equations in 11 variables and 19 parameters, 3 of which are of interest for symbolic treatment. The model also imposes positivity conditions on all variables and parameters. We apply combinations of symbolic computation methods designed for mixed equality/inequality systems, specifically virtual substitution, lazy real triangularization and cylindrical algebraic decomposition, as well as a simplification technique adapted from Gaussian elimination and graph theory. We are able to determine multistationarity of our main example over a 2-dimensional parameter space. We also study a second MAPK model and a symbolic grid sampling technique which can locate such regions in 3-dimensional parameter space
Identifying the parametric occurrence of multiple steady states for some biological networks
We consider a problem from biological network analysis of determining regions in a parameter space over which there are multiple steady states for positive real values of variables and parameters. We describe multiple approaches to address the problem using tools from Symbolic Computation. We describe how progress was made to achieve semi-algebraic descriptions of the multistationarity regions of parameter space, and compare symbolic and numerical methods. The biological networks studied are models of the mitogen-activated protein kinases (MAPK) network which has already consumed considerable effort using special insights into its structure of corresponding models. Our main example is a model with 11 equations in 11 variables and 19 parameters, 3 of which are of interest for symbolic treatment. The model also imposes positivity conditions on all variables and parameters. We apply combinations of symbolic computation methods designed for mixed equality / inequality systems, specifically virtual substitution, lazy real triangularization and cylindrical algebraic decomposition, as well as a simplification technique adapted from Gaussian elimination and graph theory. We are able to determine semi-algebraic conditions for multistationarity of our main example over a 2-dimensional parameter space. We also study a second MAPK model and a symbolic grid sampling technique which can locate such regions in 3-dimensional parameter space. © 2019 Elsevier Lt
Generation and Applications of Knowledge Graphs in Systems and Networks Biology
The acceleration in the generation of data in the biomedical domain has necessitated the use of computational approaches to assist in its interpretation. However, these approaches rely on the availability of high quality, structured, formalized biomedical knowledge. This thesis has the two goals to improve methods for curation and semantic data integration to generate high granularity biological knowledge graphs and to develop novel methods for using prior biological knowledge to propose new biological hypotheses. The first two publications describe an ecosystem for handling biological knowledge graphs encoded in the Biological Expression Language throughout the stages of curation, visualization, and analysis. Further, the second two publications describe the reproducible acquisition and integration of high-granularity knowledge with low contextual specificity from structured biological data sources on a massive scale and support the semi-automated curation of new content at high speed and precision. After building the ecosystem and acquiring content, the last three publications in this thesis demonstrate three different applications of biological knowledge graphs in modeling and simulation. The first demonstrates the use of agent-based modeling for simulation of neurodegenerative disease biomarker trajectories using biological knowledge graphs as priors. The second applies network representation learning to prioritize nodes in biological knowledge graphs based on corresponding experimental measurements to identify novel targets. Finally, the third uses biological knowledge graphs and develops algorithmics to deconvolute the mechanism of action of drugs, that could also serve to identify drug repositioning candidates. Ultimately, the this thesis lays the groundwork for production-level applications of drug repositioning algorithms and other knowledge-driven approaches to analyzing biomedical experiments