Bayesian ensemble refinement by replica simulations and reweighting

We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraint should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" (BioEn) method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.Comment: Paper submitted to The Journal of Chemical Physics (15 pages, 4 figures); updated references; expanded discussions of related formalisms, error treatment, and ensemble refinement with and without replicas; appendi

A higher-order active contour model of a `gas of circles' and its application to tree crown extraction

Many image processing problems involve identifying the region in the image domain occupied by a given entity in the scene. Automatic solution of these problems requires models that incorporate significant prior knowledge about the shape of the region. Many methods for including such knowledge run into difficulties when the topology of the region is unknown a priori, for example when the entity is composed of an unknown number of similar objects. Higher-order active contours (HOACs) represent one method for the modelling of non-trivial prior knowledge about shape without necessarily constraining region topology, via the inclusion of non-local interactions between region boundary points in the energy defining the model. The case of an unknown number of circular objects arises in a number of domains, e.g. medical, biological, nanotechnological, and remote sensing imagery. Regions composed of an a priori unknown number of circles may be referred to as a `gas of circles'. In this report, we present a HOAC model of a `gas of circles'. In order to guarantee stable circles, we conduct a stability analysis via a functional Taylor expansion of the HOAC energy around a circular shape. This analysis fixes one of the model parameters in terms of the others and constrains the rest. In conjunction with a suitable likelihood energy, we apply the model to the extraction of tree crowns from aerial imagery, and show that the new model outperforms other techniques

Optimal design of dilution experiments under volume constraints

The paper develops methods to construct a one-stage optimal design of dilution experiments under the total available volume constraint typical for bio-medical applications. We consider various design criteria based on the Fisher information both is Bayesian and non-Bayasian settings and show that the optimal design is typically one-atomic meaning that all the dilutions should be of the same size. The main tool is variational analysis of functions of a measure and the corresponding steepest descent type numerical methods. Our approach is generic in the sense that it allows for inclusion of additional constraints and cost components, like the cost of materials and of the experiment itself.Comment: 29 pages, 10 figure