ABC likelihood-freee methods for model choice in Gibbs random fields

Gibbs random fields (GRF) are polymorphous statistical models that can be used to analyse different types of dependence, in particular for spatially correlated data. However, when those models are faced with the challenge of selecting a dependence structure from many, the use of standard model choice methods is hampered by the unavailability of the normalising constant in the Gibbs likelihood. In particular, from a Bayesian perspective, the computation of the posterior probabilities of the models under competition requires special likelihood-free simulation techniques like the Approximate Bayesian Computation (ABC) algorithm that is intensively used in population genetics. We show in this paper how to implement an ABC algorithm geared towards model choice in the general setting of Gibbs random fields, demonstrating in particular that there exists a sufficient statistic across models. The accuracy of the approximation to the posterior probabilities can be further improved by importance sampling on the distribution of the models. The practical aspects of the method are detailed through two applications, the test of an iid Bernoulli model versus a first-order Markov chain, and the choice of a folding structure for two proteins.Comment: 19 pages, 5 figures, to appear in Bayesian Analysi

Algorithm engineering for optimal alignment of protein structure distance matrices

Protein structural alignment is an important problem in computational biology. In this paper, we present first successes on provably optimal pairwise alignment of protein inter-residue distance matrices, using the popular Dali scoring function. We introduce the structural alignment problem formally, which enables us to express a variety of scoring functions used in previous work as special cases in a unified framework. Further, we propose the first mathematical model for computing optimal structural alignments based on dense inter-residue distance matrices. We therefore reformulate the problem as a special graph problem and give a tight integer linear programming model. We then present algorithm engineering techniques to handle the huge integer linear programs of real-life distance matrix alignment problems. Applying these techniques, we can compute provably optimal Dali alignments for the very first time

CLP-based protein fragment assembly

The paper investigates a novel approach, based on Constraint Logic Programming (CLP), to predict the 3D conformation of a protein via fragments assembly. The fragments are extracted by a preprocessor-also developed for this work- from a database of known protein structures that clusters and classifies the fragments according to similarity and frequency. The problem of assembling fragments into a complete conformation is mapped to a constraint solving problem and solved using CLP. The constraint-based model uses a medium discretization degree Ca-side chain centroid protein model that offers efficiency and a good approximation for space filling. The approach adapts existing energy models to the protein representation used and applies a large neighboring search strategy. The results shows the feasibility and efficiency of the method. The declarative nature of the solution allows to include future extensions, e.g., different size fragments for better accuracy.Comment: special issue dedicated to ICLP 201