Section: New Results

Sequence and structure annotation

Participants : François Coste, Aymeric Antoine-Lorquin, Catherine Belleannée, Guillaume Collet, Clovis Galiez, Laurent Miclet, Jacques Nicolas.

Amplitude Spectrum Distance: measuring the global shape divergence of protein fragments. We introduce here the Amplitude Spectrum Distance (ASD), a novel way of comparing protein fragments based on the discrete Fourier transform of their $C_{\alpha }$ distance matrix. Defined as the distance between their amplitude spectra, ASD can be computed efficiently and provides a parameter-free measure of the global shape dissimilarity of two fragments. ASD inherits from nice theoretical properties, making it tolerant to shifts, insertions, deletions, circular permutations or sequence reversals while satisfying the triangle inequality. The practical interest of ASD with respect to RMSD, ${\text{RMSD}}_{\text{d}}$, BC and TM scores is illustrated through zinc finger retrieval experiments and concrete structure examples. The benefits of ASD are also illustrated by two additional clustering experiments: domain linkers fragments and complementarity-determining regions of antibodies. [Clovis Galiez, François Coste] [19]

Structural conservation of remote homologues: better and further in contact fragments. We address a basic question on sequence-structure relationships in proteins: does a protein sequence depict a structure with a uniform faithfulness all along the sequence ? We investigate this question by defining contact fragments. This study suggests that sequence homologs of CF are significantly more faithful to structure than randomly chosen fragments, so that CF carry a strong sequence-structure relationship, allowing them to be used as accurate building blocks for structure prediction. [Clovis Galiez, François Coste] [26]

VIRALpro: a tool to identify viral capsid and tail sequences. Not only sequence data continues to outpace annotation information, but the problem is further exacerbated when organisms are underrepresented in the annotation databases. This is the case with non human-pathogenic viruses which occur frequently in metagenomic projects. Thus there is a need for tools capable of detecting and classifying viral sequences. We describe VIRALpro a new effective tool for identifying capsid and tail protein sequences, which are the cornerstones toward viral sequence annotation and viral genome classification. [Clovis Galiez, François Coste] [18]

Finding Optimal Discretization Orders for Molecular Distance Geometry. The Molecular Distance Geometry Problem (MDGP) is the problem of finding the possible conformations of a molecule by exploiting available information about distances between some atom pairs. Under minimal assumptions the MDGP can be discretized so that the search domain of the problem becomes a tree that can be explored by using an interval Branch & Prune (iBP) algorithm. In this context, the discretization assumptions are strongly dependent on the atomic ordering, which can also impact the computational cost of the iBP algorithm. In this work, we propose a new partial discretization order for protein backbones. This new atomic order optimizes a set of objectives that aim at improving the iBP performances. The optimization of the objectives is performed by Answer Set Programming (ASP), which allows to express the problem by a set of logical constraints. The comparison with previously proposed orders for protein backbones shows that this new discretization order makes iBP perform more efficiently. [Jacques Nicolas] [34]

From formal concepts to analogical complexes. Reasoning by analogy is an important component of common sense reasoning whose formalization has undergone recent improvements with the logical and algebraic study of the analogical proportion. The starting point of this study considers analogical proportions on a formal context. We introduce analogical complexes, a companion of formal concepts formed by using analogy between four subsets of objects in place of the initial binary relation. They represent subsets of objects and attributes that share a maximal analogical relation. We show that the set of all complexes can be structured in an analogical complex lattice and give explicit formulae for the computation of their infimum and supremum. [Laurent Miclet, Jacques Nicolas] [27]

Comparison of the targets obtained by a scoring matrix and by a regular expression. Application to the search for LXR binding sites. In bioinformatics, it is a common task to search for new instances of a pattern built from a set of reference sequences. For the simplest and most frequent cases, patterns are represented in two ways : regular expression or scoring matrix. Since both representations seem to be used indifferently in pratice, one may wonder if they have any impact on the result. This study compares hits obtained with scoring matrices or by regular expressions allowing up to two substitutions. It shows that, in our LXR study, sequences found by a scoring matrix are closer to the targeted hits than sequences found by a regular expression. [Aymeric Antoine-Lorquin, Jacques Nicolas, Catherine Belleannée] [29]

Finding and Characterizing Repeats in Plant Genomes. Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of available softwares that can help biologists to look for these repeats and check some hypothetical models intended to characterize their structures. Since transposable elements are a major source of repeats in plants, we have provided a whole section on this topic as well as a selection of the main existing softwares. In order to better understand how they work and how repeats may be efficiently found in genomes, the rest of the chapter is devoted to the foundations of the search for repeats and more complex patterns. We first introduce the key concepts that are useful for understanding the current state of the art in playing with words, applied to genomic sequences. In fact, biologists need to represent more complex entities where a repeat family is built on more abstract structures, including direct or inverted small repeats, motifs, composition constraints as well as ordering and distance constraints between these elementary blocks. The last section introduces concepts and practical tools that can be used to reach this syntactic level in biological sequence analysis. [Jacques Nicolas] [35]