167 research outputs found
Determining Structurally Identifiable Parameter Combinations Using Subset Profiling
Identifiability is a necessary condition for successful parameter estimation
of dynamic system models. A major component of identifiability analysis is
determining the identifiable parameter combinations, the functional forms for
the dependencies between unidentifiable parameters. Identifiable combinations
can help in model reparameterization and also in determining which parameters
may be experimentally measured to recover model identifiability. Several
numerical approaches to determining identifiability of differential equation
models have been developed, however the question of determining identifiable
combinations remains incompletely addressed. In this paper, we present a new
approach which uses parameter subset selection methods based on the Fisher
Information Matrix, together with the profile likelihood, to effectively
estimate identifiable combinations. We demonstrate this approach on several
example models in pharmacokinetics, cellular biology, and physiology
In Silico Synchronization of Cellular Populations Through Expression Data Deconvolution
Cellular populations are typically heterogenous collections of cells at
different points in their respective cell cycles, each with a cell cycle time
that varies from individual to individual. As a result, true single-cell
behavior, particularly that which is cell-cycle--dependent, is often obscured
in population-level (averaged) measurements. We have developed a simple
deconvolution method that can be used to remove the effects of asynchronous
variability from population-level time-series data. In this paper, we summarize
some recent progress in the development and application of our approach, and
provide technical updates that result in increased biological fidelity. We also
explore several preliminary validation results and discuss several ongoing
applications that highlight the method's usefulness for estimating parameters
in differential equation models of single-cell gene regulation.Comment: accepted for the 48th ACM/IEEE Design Automation Conferenc
Identifiability results for several classes of linear compartment models
Identifiability concerns finding which unknown parameters of a model can be
estimated from given input-output data. If some subset of the parameters of a
model cannot be determined given input-output data, then we say the model is
unidentifiable. In past work we identified a class of models, that we call
identifiable cycle models, which are not identifiable but have the simplest
possible identifiable functions (so-called monomial cycles). Here we show how
to modify identifiable cycle models by adding inputs, adding outputs, or
removing leaks, in such a way that we obtain an identifiable model. We also
prove a constructive result on how to combine identifiable models, each
corresponding to strongly connected graphs, into a larger identifiable model.
We apply these theoretical results to several real-world biological models from
physiology, cell biology, and ecology.Comment: 7 figure
Linking Decision Theory and Quantitative Microbial Risk Assessment: Tradeoffs Between Compliance and Efficacy for Waterborne Disease Interventions
Achieving health gains from the U.N. Sustainable Development Goals of universal coverage for water and sanitation will require interventions that can be widely adopted and maintained. Effectivenessâhow an intervention performs based on actual useâas opposed to efficacy will therefore be central to evaluations of new and existing interventions. Incomplete complianceâwhen people do not always use the intervention and are therefore exposed to contaminationâis thought to be responsible for the lowerâthanâexpected risk reductions observed from water, sanitation, and hygiene interventions based on their efficacy at removing pathogens. We explicitly incorporated decision theory into a quantitative microbial risk assessment model. Specifically, we assume that the usability of household water treatment (HWT) devices (filters and chlorine) decreases as they become more efficacious due to issues such as taste or flow rates. Simulations were run to examine the tradeoff between device efficacy and usability. For most situations, HWT interventions that trade lower efficacy (i.e., remove less pathogens) for higher compliance (i.e., better usability) contribute substantial reductions in diarrheal disease risk compared to devices meeting current World Health Organization efficacy guidelines. Recommendations that take into account both the behavioral and microbiological properties of treatment devices are likely to be more effective at reducing the burden of diarrheal disease than current standards that only consider efficacy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/1/risa13381.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/2/risa13381-sup-0001-Appendix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151809/3/risa13381_am.pd
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