8,267 research outputs found
Optimal experimental design for mathematical models of haematopoiesis.
The haematopoietic system has a highly regulated and complex structure in which cells are organized to successfully create and maintain new blood cells. It is known that feedback regulation is crucial to tightly control this system, but the specific mechanisms by which control is exerted are not completely understood. In this work, we aim to uncover the underlying mechanisms in haematopoiesis by conducting perturbation experiments, where animal subjects are exposed to an external agent in order to observe the system response and evolution. We have developed a novel Bayesian hierarchical framework for optimal design of perturbation experiments and proper analysis of the data collected. We use a deterministic model that accounts for feedback and feedforward regulation on cell division rates and self-renewal probabilities. A significant obstacle is that the experimental data are not longitudinal, rather each data point corresponds to a different animal. We overcome this difficulty by modelling the unobserved cellular levels as latent variables. We then use principles of Bayesian experimental design to optimally distribute time points at which the haematopoietic cells are quantified. We evaluate our approach using synthetic and real experimental data and show that an optimal design can lead to better estimates of model parameters
An Induced Natural Selection Heuristic for Finding Optimal Bayesian Experimental Designs
Bayesian optimal experimental design has immense potential to inform the
collection of data so as to subsequently enhance our understanding of a variety
of processes. However, a major impediment is the difficulty in evaluating
optimal designs for problems with large, or high-dimensional, design spaces. We
propose an efficient search heuristic suitable for general optimisation
problems, with a particular focus on optimal Bayesian experimental design
problems. The heuristic evaluates the objective (utility) function at an
initial, randomly generated set of input values. At each generation of the
algorithm, input values are "accepted" if their corresponding objective
(utility) function satisfies some acceptance criteria, and new inputs are
sampled about these accepted points. We demonstrate the new algorithm by
evaluating the optimal Bayesian experimental designs for the previously
considered death, pharmacokinetic and logistic regression models. Comparisons
to the current "gold-standard" method are given to demonstrate the proposed
algorithm as a computationally-efficient alternative for moderately-large
design problems (i.e., up to approximately 40-dimensions)
Evidence functions: a compositional approach to information
The discrete case of Bayes’ formula is considered the paradigm of information acquisition. Prior and posterior probability functions, as well as likelihood functions, called evidence functions, are compositions following the Aitchison geometry of the simplex, and have thus vector character. Bayes’ formula becomes a vector addition. The Aitchison norm of an evidence function is introduced as a scalar measurement of information. A fictitious fire scenario serves as illustration. Two different inspections of affected houses are considered. Two questions are addressed: (a) which is the information provided by the outcomes of inspections, and (b) which is the most informative inspection.Peer Reviewe
Evidence functions: a compositional approach to information
The discrete case of Bayes’ formula is considered the paradigm of information acquisition. Prior and posterior probability functions, as well as likelihood functions, called evidence functions, are compositions following the Aitchison geometry of the simplex, and have thus vector character. Bayes’ formula becomes a vector addition. The Aitchison norm of an evidence function is introduced as a scalar measurement of information. A fictitious fire scenario serves as illustration. Two different inspections of affected houses are considered. Two questions are addressed: (a) which is the information provided by the outcomes of inspections, and (b) which is the most informative inspection.Peer ReviewedPostprint (author's final draft
Gaussian process surrogates for failure detection: a Bayesian experimental design approach
An important task of uncertainty quantification is to identify {the
probability of} undesired events, in particular, system failures, caused by
various sources of uncertainties. In this work we consider the construction of
Gaussian {process} surrogates for failure detection and failure probability
estimation. In particular, we consider the situation that the underlying
computer models are extremely expensive, and in this setting, determining the
sampling points in the state space is of essential importance. We formulate the
problem as an optimal experimental design for Bayesian inferences of the limit
state (i.e., the failure boundary) and propose an efficient numerical scheme to
solve the resulting optimization problem. In particular, the proposed
limit-state inference method is capable of determining multiple sampling points
at a time, and thus it is well suited for problems where multiple computer
simulations can be performed in parallel. The accuracy and performance of the
proposed method is demonstrated by both academic and practical examples
A Stein variational Newton method
Stein variational gradient descent (SVGD) was recently proposed as a general
purpose nonparametric variational inference algorithm [Liu & Wang, NIPS 2016]:
it minimizes the Kullback-Leibler divergence between the target distribution
and its approximation by implementing a form of functional gradient descent on
a reproducing kernel Hilbert space. In this paper, we accelerate and generalize
the SVGD algorithm by including second-order information, thereby approximating
a Newton-like iteration in function space. We also show how second-order
information can lead to more effective choices of kernel. We observe
significant computational gains over the original SVGD algorithm in multiple
test cases.Comment: 18 pages, 7 figure
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