A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances

Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances (Boden et al., 2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower misclassification rate when used with Support Vector Machines (SVMs) (On-odera and Shibuya, 2013), We confirm by independent experiments these two results, and propose in this article to use a coverage criterion (Benson and Mak, 2008, Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both cases in order to design better seed patterns. We show first how this coverage criterion can be directly measured by a full automaton-based approach. We then illustrate how this criterion performs when compared with two other criteria frequently used, namely the single-hit and multiple-hit criteria, through correlation coefficients with the correct classification/the true distance. At the end, for alignment-free distances, we propose an extension by adopting the coverage criterion, show how it performs, and indicate how it can be efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017

A Coverage Criterion for Spaced Seeds and its Applications to Support Vector Machine String Kernels and k-Mer Distances

Spaced seeds have been recently shown to not only detect more alignments, but also to give a more accurate measure of phylogenetic distances (Boden et al., 2013, Horwege et al., 2014, Leimeister et al., 2014), and to provide a lower misclassification rate when used with Support Vector Machines (SVMs) (On-odera and Shibuya, 2013), We confirm by independent experiments these two results, and propose in this article to use a coverage criterion (Benson and Mak, 2008, Martin, 2013, Martin and No{\'e}, 2014), to measure the seed efficiency in both cases in order to design better seed patterns. We show first how this coverage criterion can be directly measured by a full automaton-based approach. We then illustrate how this criterion performs when compared with two other criteria frequently used, namely the single-hit and multiple-hit criteria, through correlation coefficients with the correct classification/the true distance. At the end, for alignment-free distances, we propose an extension by adopting the coverage criterion, show how it performs, and indicate how it can be efficiently computed.Comment: http://online.liebertpub.com/doi/abs/10.1089/cmb.2014.017

Efficient exact motif discovery

Motivation: The motif discovery problem consists of finding over-represented patterns in a collection of biosequences. It is one of the classical sequence analysis problems, but still has not been satisfactorily solved in an exact and efficient manner. This is partly due to the large number of possibilities of defining the motif search space and the notion of over-representation. Even for well-defined formalizations, the problem is frequently solved in an ad hoc manner with heuristics that do not guarantee to find the best motif

Exact distribution of a pattern in a set of random sequences generated by a Markov source: applications to biological data

<p>Abstract</p> <p>Background</p> <p>In bioinformatics it is common to search for a pattern of interest in a potentially large set of rather short sequences (upstream gene regions, proteins, exons, etc.). Although many methodological approaches allow practitioners to compute the distribution of a pattern count in a random sequence generated by a Markov source, no specific developments have taken into account the counting of occurrences in a set of independent sequences. We aim to address this problem by deriving efficient approaches and algorithms to perform these computations both for low and high complexity patterns in the framework of homogeneous or heterogeneous Markov models.</p> <p>Results</p> <p>The latest advances in the field allowed us to use a technique of optimal Markov chain embedding based on deterministic finite automata to introduce three innovative algorithms. Algorithm 1 is the only one able to deal with heterogeneous models. It also permits to avoid any product of convolution of the pattern distribution in individual sequences. When working with homogeneous models, Algorithm 2 yields a dramatic reduction in the complexity by taking advantage of previous computations to obtain moment generating functions efficiently. In the particular case of low or moderate complexity patterns, Algorithm 3 exploits power computation and binary decomposition to further reduce the time complexity to a logarithmic scale. All these algorithms and their relative interest in comparison with existing ones were then tested and discussed on a toy-example and three biological data sets: structural patterns in protein loop structures, PROSITE signatures in a bacterial proteome, and transcription factors in upstream gene regions. On these data sets, we also compared our exact approaches to the tempting approximation that consists in concatenating the sequences in the data set into a single sequence.</p> <p>Conclusions</p> <p>Our algorithms prove to be effective and able to handle real data sets with multiple sequences, as well as biological patterns of interest, even when the latter display a high complexity (PROSITE signatures for example). In addition, these exact algorithms allow us to avoid the edge effect observed under the single sequence approximation, which leads to erroneous results, especially when the marginal distribution of the model displays a slow convergence toward the stationary distribution. We end up with a discussion on our method and on its potential improvements.</p

Waiting times for clumps of patterns and for structured motifs in random sequences

AbstractThis paper provides exact probability results for waiting times associated with occurrences of two types of motifs in a random sequence. First, we provide an explicit expression for the probability generating function of the interarrival time between two clumps of a pattern. It allows, in particular, to measure the quality of the Poisson approximation which is currently used for evaluation of the distribution of the number of clumps of a pattern. Second, we provide explicit expressions for the probability generating functions of both the waiting time until the first occurrence, and the interarrival time between consecutive occurrences, of a structured motif. Distributional results for structured motifs are of interest in genome analysis because such motifs are promoter candidates. As an application, we determine significant structured motifs in a data set of DNA regulatory sequences

The Target-Based Utility Model. The role of Copulas and of Non-Additive Measures

My studies and my Ph.D. thesis deal with topics that recently emerged in the field of decisions under risk and uncertainty. In particular, I deal with the "target-based approach" to utility theory. A rich literature has been devoted in the last decade to this approach to economic decisions: originally, interest had been focused on the "single-attribute" case and, more recently, extensions to "multi-attribute" case have been studied. This literature is still growing, with a main focus on applied aspects. I will, on the contrary, focus attention on some aspects of theoretical type, related with the multi-attribute case. Various mathematical concepts, such as non-additive measures, aggregation functions, multivariate probability distributions, and notions of stochastic dependence emerge in the formulation and the analysis of target-based models. Notions in the field of non-additive measures and aggregation functions are quite common in the modern economic literature. They have been used to go beyond the classical principle of maximization of expected utility in decision theory. These notions, furthermore, are used in game theory and multi-criteria decision aid. Along my work, on the contrary, I show how non-additive measures and aggregation functions emerge in a natural way in the frame of the target-based approach to classical utility theory, when considering the multi-attribute case. Furthermore they combine with the analysis of multivariate probability distributions and with concepts of stochastic dependence. The concept of copula also constitutes a very important tool for this work, mainly for two purposes. The first one is linked to the analysis of target-based utilities, the other one is in the comparison between classical stochastic order and the concept of "stochastic precedence". This topic finds its application in statistics as well as in the study of Markov Models linked to waiting times to occurrences of words in random sampling of letters from an alphabet. In this work I give a generalization of the concept of stochastic precedence and we discuss its properties on the basis of properties of the connecting copulas of the variables. Along this work I also trace connections to reliability theory, whose aim is studying the lifetime of a system through the analysis of the lifetime of its components. The target-based model finds an application in representing the behavior of the whole system by means of the interaction of its components