Biomedical subjects

Stéphane Guindon

Publications and source records attributed to Stéphane Guindon.

5 recordsLinked to original sources

PubMed2006

Proceedings of the SMBE Tri-National Young Investigators' Workshop 2005. Control of the false discovery rate applied to the detection of positively selected amino acid sites.

In this article, we consider the probabilistic identification of amino acid positions that evolve under positive selection as a multiple hypothesis testing problem. The null hypothesis "H0,s: site s evolves under a negative selection or under a neutral process of evolution" is tested at each codon site of the alignment of homologous coding sequences. Standard hypothesis testing is based on the control of the expected proportion of falsely rejected null hypotheses or type-I error rate. As the number of tests increases, however, the power of an individual test may become unacceptably low. Recent advances in statistics have shown that the false discovery rate--in this case, the expected proportion of sites that do not evolve under positive selection among those that are estimated to evolve under this selection regime--is a quantity that can be controlled. Keeping the proportion of false positives low among the significant results generally leads to an increase in power. In this article, we show that controlling the false detection rate is relevant when searching for positively selected sites. We also compare this new approach to traditional methods using extensive simulations.

Amino Acids↗

PubMed2005

PHYML Online--a web server for fast maximum likelihood-based phylogenetic inference.

PHYML Online is a web interface to PHYML, a software that implements a fast and accurate heuristic for estimating maximum likelihood phylogenies from DNA and protein sequences. This tool provides the user with a number of options, e.g. nonparametric bootstrap and estimation of various evolutionary parameters, in order to perform comprehensive phylogenetic analyses on large datasets in reasonable computing time. The server and its documentation are available at http://atgc.lirmm.fr/phyml.

Algorithms↗

PubMed2004

Modeling the site-specific variation of selection patterns along lineages.

The unambiguous footprint of positive Darwinian selection in protein-coding DNA sequences is revealed by an excess of nonsynonymous substitutions over synonymous substitutions compared with the neutral expectation. Methods for analyzing the patterns of nonsynonymous and synonymous substitutions usually rely on stochastic models in which the selection regime may vary across the sequence but remains constant across lineages for any amino acid position. Despite some work that has relaxed the constraint that selection patterns remain constant over time, no model provides a strong statistical framework to deal with switches between selection processes at individual sites during the course of evolution. This paper describes an approach that allows the site-specific selection process to vary along lineages of a phylogenetic tree. The parameters of the switching model of codon substitution are estimated by using maximum likelihood. The analysis of eight HIV-1 env homologous sequence data sets shows that this model provides a significantly better fit to the data than one that does not take into account switches between selection patterns in the phylogeny at individual sites. We also provide strong evidence that the strength and the frequency of occurrence of selection might not be estimated accurately when the site-specific variation of selection regimes is ignored.

Amino Acid Substitution↗

PubMed2003

A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood.

The increase in the number of large data sets and the complexity of current probabilistic sequence evolution models necessitates fast and reliable phylogeny reconstruction methods. We describe a new approach, based on the maximum- likelihood principle, which clearly satisfies these requirements. The core of this method is a simple hill-climbing algorithm that adjusts tree topology and branch lengths simultaneously. This algorithm starts from an initial tree built by a fast distance-based method and modifies this tree to improve its likelihood at each iteration. Due to this simultaneous adjustment of the topology and branch lengths, only a few iterations are sufficient to reach an optimum. We used extensive and realistic computer simulations to show that the topological accuracy of this new method is at least as high as that of the existing maximum-likelihood programs and much higher than the performance of distance-based and parsimony approaches. The reduction of computing time is dramatic in comparison with other maximum-likelihood packages, while the likelihood maximization ability tends to be higher. For example, only 12 min were required on a standard personal computer to analyze a data set consisting of 500 rbcL sequences with 1,428 base pairs from plant plastids, thus reaching a speed of the same order as some popular distance-based and parsimony algorithms. This new method is implemented in the PHYML program, which is freely available on our web page: http://www.lirmm.fr/w3ifa/MAAS/.

Algorithms↗

PubMed2002

Efficient biased estimation of evolutionary distances when substitution rates vary across sites.

This paper deals with phylogenetic inference when the variability of substitution rates across sites (VRAS) is modeled by a gamma distribution. We show that underestimating VRAS, which results in underestimates for the evolutionary distances between sequences, usually improves the topological accuracy of phylogenetic tree inference by distance-based methods, especially when the molecular clock holds. We propose a method to estimate the gamma shape parameter value which is most suited for tree topology inference, given the sequences at hand. This method is based on the pairwise evolutionary distances between sequences and allows one to reconstruct the phylogeny of a high number of taxa (>1,000). Simulation results show that the topological accuracy is highly improved when using the gamma shape parameter value given by our method, compared with the true (unknown) value which was used to generate the data. Furthermore, when VRAS is high, the topological accuracy of our distance-based method is better than that of a maximum likelihood approach. Finally, a data set of Maoricicada species sequences is analyzed, which confirms the advantage of our method.

Algorithms↗