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Biomedical subjects

Grégory Nuel

Publications and source records attributed to Grégory Nuel.

5 recordsLinked to original sources

Pattern statistics on Markov chains and sensitivity to parameter estimation.

BACKGROUND: In order to compute pattern statistics in computational biology a Markov model is commonly used to take into account the sequence composition. Usually its parameter must be estimated. The aim of this paper is to determine how sensitive these statistics are to parameter estimation, and what are the consequences of this variability on pattern studies (finding the most over-represented words in a genome, the most significant common words to a set of sequences,...). RESULTS: In the particular case where pattern statistics (overlap counting only) computed through binomial approximations we use the delta-method to give an explicit expression of sigma, the standard deviation of a pattern statistic. This result is validated using simulations and a simple pattern study is also considered. CONCLUSION: We establish that the use of high order Markov model could easily lead to major mistakes due to the high sensitivity of pattern statistics to parameter estimation.

Journal Article↗

Effective p-value computations using Finite Markov Chain Imbedding (FMCI): application to local score and to pattern statistics.

The technique of Finite Markov Chain Imbedding (FMCI) is a classical approach to complex combinatorial problems related to sequences. In order to get efficient algorithms, it is known that such approaches need to be first rewritten using recursive relations. We propose here to give here a general recursive algorithms allowing to compute in a numerically stable manner exact Cumulative Distribution Function (CDF) or complementary CDF (CCDF). These algorithms are then applied in two particular cases: the local score of one sequence and pattern statistics. In both cases, asymptotic developments are derived. For the local score, our new approach allows for the very first time to compute exact p-values for a practical study (finding hydrophobic segments in a protein database) where only approximations were available before. In this study, the asymptotic approximations appear to be completely unreliable for 99.5% of the considered sequences. Concerning the pattern statistics, the new FMCI algorithms dramatically outperform the previous ones as they are more reliable, easier to implement, faster and with lower memory requirements.

Journal Article↗

S-SPatt: simple statistics for patterns on Markov chains.

SUMMARY: S-SPatt allows the counting of patterns occurrences in text files and, assuming these texts are generated from a random Markovian source, the computation of the P-value of a given observation using a simple binomial approximation.

Algorithms↗

seq++: analyzing biological sequences with a range of Markov-related models.

SUMMARY: The seq++ package offers a reference set of programs and an extensible library to biologists and developers working on sequence statistics. Its generality arises from the ability to handle sequences described with any alphabet (nucleotides, amino acids, codons and others). seq++ enables sequence modelling with various types of Markov models, including variable length Markov models and the newly developed parsimonious Markov models, all of them potentially phased. Simulation modules are supplied for Monte Carlo methods. Hence, this toolbox allows the study of any biological process which can be described by a series of states taken from a finite set.

Algorithms↗

AMIGene: Annotation of MIcrobial Genes.

UNLABELLED: AMIGene (Annotation of MIcrobial Genes) is an application for automatically identifying the most likely coding sequences (CDSs) in a large contig or a complete bacterial genome sequence. The first step in AMIGene is dedicated to the construction of Markov models that fit the input genomic data (i.e. the gene model), followed by the combination of well-known gene-finding methods and an heuristic approach for the selection of the most likely CDSs. The web interface allows the user to select one or several gene models applied to the analysis of the input sequence by the AMIGene program and to visualize the list of predicted CDSs graphically and in a downloadable text format. The AMIGene web site is accessible at the following address: http://www.genoscope.cns.fr/agc/tools/amigene/index.html ( CONTACT: sbocs@genoscope.cns.fr).

Computer Graphics↗