Modeling the velocity of evolving lineages and predicting dispersal patterns.

Accurate estimation of the dispersal velocity or speed of evolving organisms is no mean feat. In fact, existing probabilistic models in phylogeography or spatial population genetics generally do not provide an adequate framework to define velocity in a relevant manner. For instance, the very concept of instantaneous speed simply does not exist under one of the most popular approaches that models the evolution of spatial coordinates as Brownian trajectories running along a phylogeny [30]. Here, we introduce a new family of models - the so-called "Phylogenetic Integrated Velocity" (PIV) models - that use Gaussian processes to explicitly model the velocity of evolving lineages instead of focusing on the fluctuation of spatial coordinates over time. We describe the properties of these models and show an increased accuracy of velocity estimates compared to previous approaches. Analyses of West Nile virus data in the U.S.A. indicate that PIV models provide sensible predictions of the dispersal of evolving pathogens at a one-year time horizon. These results demonstrate the feasibility and relevance of predictive phylogeography in monitoring epidemics in time and space.

EvoLaps: a web interface to visualize continuous phylogeographic reconstructions.

BACKGROUND: Phylogeographic reconstructions serve as a basis to understand the spread and evolution of pathogens. Visualization of these reconstructions often lead to complex graphical representations which are difficult to interpret. RESULT: We present EvoLaps, a user-friendly web interface to visualize phylogeographic reconstructions based on the analysis of latitude/longitude coordinates with various clustering levels. EvoLaps also produces transition diagrams that provide concise and easy to interpret summaries of phylogeographic reconstructions. CONCLUSION: The main contribution of EvoLaps is to assemble known numerical and graphical methods/tools into a user-friendly interface dedicated to the visualization and edition of evolutionary scenarios based on continuous phylogeographic reconstructions. EvoLaps is freely usable at www.evolaps.org .

PastView: a user-friendly interface to explore ancestral scenarios.

BACKGROUND: Ancestral character states computed from the combination of phylogenetic trees with extrinsic traits are used to decipher evolutionary scenarios in various research fields such as phylogeography, epidemiology, and ecology. Despite the existence of powerful methods and software in ancestral character state inference, difficulties may arise when interpreting the outputs of such inferences. The growing complexity of data (trees, annotations), the diversity of optimization criteria for computing trees and ancestral character states, the combinatorial explosion of potential evolutionary scenarios if some ancestral characters states do not stand out clearly from others, requires the design of new methods to explore associations of phylogenetic trees with extrinsic traits, to ease the visualization and interpretation of evolutionary scenarios. RESULT: We developed PastView, a user-friendly interface that includes numerical and graphical features to help users to import and/or compute ancestral character states from discrete variables and extract ancestral scenarios as sets of successive transitions of character states from the tree root to its leaves. PastView provides summarized views such as transition maps and integrates comparative tools to highlight agreements or discrepancies between methods of ancestral annotations inference. CONCLUSION: The main contribution of PastView is to assemble known numerical and graphical methods into a multi-maps graphical user interface dedicated to the computing, searching and viewing of evolutionary scenarios based on phylogenetic trees and ancestral character states. PastView is available publicly as a standalone software on www.pastview.org .

Phylogeography of Puumala orthohantavirus in Europe.

Puumala virus is an RNA virus hosted by the bank vole (Myodes glareolus) and is today present in most European countries. Whilst it is generally accepted that hantaviruses have been tightly co-evolving with their hosts, Puumala virus (PUUV) evolutionary history is still controversial and so far has not been studied at the whole European level. This study attempts to reconstruct the phylogeographical spread of modern PUUV throughout Europe during the last postglacial period in the light of an upgraded dataset of complete PUUV small (S) segment sequences and by using most recent computational approaches. Taking advantage of the knowledge on the past migrations of its host, we identified at least three potential independent dispersal routes of PUUV during postglacial recolonization of Europe by the bank vole. From the Alpe-Adrian region (Balkan, Austria, and Hungary) to Western European countries (Germany, France, Belgium, and Netherland), and South Scandinavia. From the vicinity of Carpathian Mountains to the Baltic countries and to Poland, Russia, and Finland. The dissemination towards Denmark and North Scandinavia is more hypothetical and probably involved several independent streams from south and north Fennoscandia.

RecPhyloXML: a format for reconciled gene trees.

Motivation: A reconciliation is an annotation of the nodes of a gene tree with evolutionary events-for example, speciation, gene duplication, transfer, loss, etc.-along with a mapping onto a species tree. Many algorithms and software produce or use reconciliations but often using different reconciliation formats, regarding the type of events considered or whether the species tree is dated or not. This complicates the comparison and communication between different programs. Results: Here, we gather a consortium of software developers in gene tree species tree reconciliation to propose and endorse a format that aims to promote an integrative-albeit flexible-specification of phylogenetic reconciliations. This format, named recPhyloXML, is accompanied by several tools such as a reconciled tree visualizer and conversion utilities. Availability and implementation: http://phylariane.univ-lyon1.fr/recphyloxml/.

A geography-aware reconciliation method to investigate diversification patterns in host/parasite interactions.

Cospeciation studies aim at investigating whether hosts and symbionts speciate simultaneously or whether the associations diversify through host shifts. This problem is often tackled through reconciliation analyses that map the symbiont phylogeny onto the host phylogeny by mixing different types of diversification events. These reconciliations can be difficult to interpret and are not always biologically realistic. Researchers have underlined that the biogeographic histories of both hosts and symbionts influence the probability of cospeciation and host switches, but up to now no reconciliation software integrates geographic data. We present a new functionality in the Mowgli software that bridges this gap. The user can provide geographic information on both the host and symbiont extant and ancestral taxa. Constraints in the reconciliation algorithm have been implemented to generate biologically realistic codiversification scenarios. We apply our method to the fig/fig wasp association and infer diversification scenarios that differ from reconciliations ignoring geographic information. In addition, we updated the reconciliation viewer SylvX to visualize ancestral character states on the phylogenetic trees and highlight parts of reconciliations that are geographically inconsistent when not accounting for geographic constraints. We suggest that the comparison of reconciliations obtained with and without such constraints can help solving ambiguities in the biogeographic histories of the partners. With the development of robust methods in historical biogeography, and the advent of next-generation sequencing that leads to better-resolved trees, a geography-aware reconciliation method represents a substantial advance that is likely to be useful to researchers studying the evolution of biotic interactions and biogeography.

SylvX: a viewer for phylogenetic tree reconciliations.

MOTIVATION: Reconciliation methods aim at recovering the evolutionary processes that shaped the history of a given gene family including events such as duplications, transfers and losses by comparing the discrepancies between the topologies of the associated gene and species trees. These methods are also used in the framework of host/parasite studies to recover co-diversification scenarios including co-speciation events, host-switches and extinctions. These evolutionary processes can be graphically represented as nested trees. These interconnected graphs can be visually messy and hard to interpret, and despite the fact that reconciliations are increasingly used, there is a shortage of tools dedicated to their graphical management. Here we present SylvX, a reconciliation viewer which implements classical phylogenetic graphic operators (swapping, highlighting, etc.) and new methods to ease interpretation and comparison of reconciliations (multiple maps, moving, shrinking sub-reconciliations). AVAILABILITY AND IMPLEMENTATION: SylvX is an open source, cross-platform, standalone editor available for Windows and Unix-like systems including OSX. It is publicly available at www.sylvx.org.

CompPhy: a web-based collaborative platform for comparing phylogenies.

BACKGROUND: Collaborative tools are of great help in conducting projects involving distant workers. Recent web technologies have helped to build such tools for jointly editing office documents and scientific data, yet none are available for handling phylogenies. Though a large number of studies and projects in evolutionary biology and systematics involve collaborations between scientists of different institutes, current tree comparison visualization software and websites are directed toward single-user access. Moreover, tree comparison functionalities are dispersed between different software that mainly focus on high level single tree visualization but to the detriment of basic tree comparison features. RESULTS: The web platform presented here, named CompPhy, intends to fill this gap by allowing collaborative work on phylogenies and by gathering simple advanced tools dedicated to tree comparison. It offers functionalities for tree edition, tree comparison, supertree inference and data management in a collaborative environment. The latter aspect is a specific feature of the platform, allowing people located in different places to work together at the same time on a common project. CompPhy thus proposes shared tree visualization, both synchronous and asynchronous tree manipulation, data exchange/storage, as well as facilities to keep track of the progress of analyses in working sessions. Specific advanced comparison tools are also available, such as consensus and supertree inference, or automated branch swaps of compared trees. As projects can be readily created and shared, CompPhy is also a tool that can be used easily to interact with students in a educational setting, either in the classroom or for assignments. CONCLUSIONS: CompPhy is the first web platform devoted to the comparison of phylogenetic trees allowing real-time distant collaboration on a phylogenetic/phylogenomic project. This application can be accessed freely with a recent browser at the following page of the ATGC bioinformatics platform: http://www.atgc-montpellier.fr/compphy/ .

Is ecological speciation a major trend in aphids? Insights from a molecular phylogeny of the conifer-feeding genus Cinara.

INTRODUCTION: In the past decade ecological speciation has been recognized as having an important role in the diversification of plant-feeding insects. Aphids are host-specialised phytophagous insects that mate on their host plants and, as such, they are prone to experience reproductive isolation linked with host plant association that could ultimately lead to species formation. The generality of such a scenario remains to be tested through macroevolutionary studies. To explore the prevalence of host-driven speciation in the diversification of the aphid genus Cinara and to investigate alternative modes of speciation, we reconstructed a phylogeny of this genus based on mitochondrial, nuclear and Buchnera aphidicola DNA sequence fragments and applied a DNA-based method of species delimitation. Using a recent software (PhyloType), we explored evolutionary transitions in host-plant genera, feeding sites and geographic distributions in the diversification of Cinara and investigated how transitions in these characters have accompanied speciation events. RESULTS: The diversification of Cinara has been constrained by host fidelity to conifer genera sometimes followed by sequential colonization onto different host species and by feeding-site specialisation. Nevertheless, our analyses suggest that, at the most, only half of the speciation events were accompanied by ecological niche shifts. The contribution of geographical isolation in the speciation process is clearly apparent in the occurrence of species from two continents in the same clades in relatively terminal positions in our phylogeny. Furthermore, in agreement with predictions from scenarios in which geographic isolation accounts for speciation events, geographic overlap between species increased significantly with time elapsed since their separation. CONCLUSIONS: The history of Cinara offers a different perspective on the mode of speciation of aphids than that provided by classic models such as the pea aphid. In this genus of aphids, the role of climate and landscape history has probably been as important as host-plant specialisation in having shaped present-day diversity.

Genetic structure and evolution of the Leishmania genus in Africa and Eurasia: what does MLSA tell us.

Leishmaniasis is a complex parasitic disease from a taxonomic, clinical and epidemiological point of view. The role of genetic exchanges has been questioned for over twenty years and their recent experimental demonstration along with the identification of interspecific hybrids in natura has revived this debate. After arguing that genetic exchanges were exceptional and did not contribute to Leishmania evolution, it is currently proposed that interspecific exchanges could be a major driving force for rapid adaptation to new reservoirs and vectors, expansion into new parasitic cycles and adaptation to new life conditions. To assess the existence of gene flows between species during evolution we used MLSA-based (MultiLocus Sequence Analysis) approach to analyze 222 Leishmania strains from Africa and Eurasia to accurately represent the genetic diversity of this genus. We observed a remarkable congruence of the phylogenetic signal and identified seven genetic clusters that include mainly independent lineages which are accumulating divergences without any sign of recent interspecific recombination. From a taxonomic point of view, the strong genetic structuration of the different species does not question the current classification, except for species that cause visceral forms of leishmaniasis (L. donovani, L. infantum and L. archibaldi). Although these taxa cause specific clinical forms of the disease and are maintained through different parasitic cycles, they are not clearly distinct and form a continuum, in line with the concept of species complex already suggested for this group thirty years ago. These results should have practical consequences concerning the molecular identification of parasites and the subsequent therapeutic management of the disease.

Searching for virus phylotypes.

MOTIVATION: Large phylogenies are being built today to study virus evolution, trace the origin of epidemics, establish the mode of transmission and survey the appearance of drug resistance. However, no tool is available to quickly inspect these phylogenies and combine them with extrinsic traits (e.g. geographic location, risk group, presence of a given resistance mutation), seeking to extract strain groups of specific interest or requiring surveillance. RESULTS: We propose a new method for obtaining such groups, which we call phylotypes, from a phylogeny having taxa (strains) annotated with extrinsic traits. Phylotypes are subsets of taxa with close phylogenetic relationships and common trait values. The method combines ancestral trait reconstruction using parsimony, with combinatorial and numerical criteria measuring tree shape characteristics and the diversity and separation of the potential phylotypes. A shuffling procedure is used to assess the statistical significance of phylotypes. All algorithms have linear time complexity. This results in low computing times, typically a few minutes for the larger data sets with a number of shuffling steps. Two HIV-1 data sets are analyzed, one of which is large, containing >3000 strains of HIV-1 subtype C collected worldwide, where the method shows its ability to recover known clusters and transmission routes, and to detect new ones. AVAILABILITY: This method and companion tools are implemented in an interactive Web interface (www.phylotype.org), which provides a wide choice of graphical views and output formats, and allows for exploratory analyses of large data sets.

ScripTree: scripting phylogenetic graphics.

UNLABELLED: There is a large amount of tools for interactive display of phylogenetic trees. However, there is a shortage of tools for the automation of tree rendering. Scripting phylogenetic graphics would enable the saving of graphical analyses involving numerous and complex tree handling operations and would allow the automation of repetitive tasks. ScripTree is a tool intended to fill this gap. It is an interpreter to be used in batch mode. Phylogenetic graphics instructions, related to tree rendering as well as tree annotation, are stored in a text file and processed in a sequential way. AVAILABILITY: ScripTree can be used online or downloaded at www.scriptree.org, under the GPL license. IMPLEMENTATION: ScripTree, written in Tcl/Tk, is a cross-platform application available for Windows and Unix-like systems including OS X. It can be used either as a stand-alone package or included in a bioinformatic pipeline and linked to a HTTP server.

OligoHeatMap (OHM): an online tool to estimate and display hybridizations of oligonucleotides onto DNA sequences.

The efficiency of molecular methods involving DNA/DNA hybridizations depends on the accurate prediction of the melting temperature (T(m)) of the duplex. Many softwares are available for T(m) calculations, but difficulties arise when one wishes to check if a given oligomer (PCR primer or probe) hybridizes well or not on more than a single sequence. Moreover, the presence of mismatches within the duplex is not sufficient to estimate specificity as it does not always significantly decrease the T(m). OHM (OligoHeatMap) is an online tool able to provide estimates of T(m) for a set of oligomers and a set of aligned sequences, not only as text files of complete results but also in a graphical way: T(m) values are translated into colors and displayed as a heat map image, either stand alone or to be used by softwares such as TreeDyn to be included in a phylogenetic tree. OHM is freely available at http://bioinfo.unice.fr/ohm/, with links to the full source code and online help.

TreeDyn: towards dynamic graphics and annotations for analyses of trees.

BACKGROUND: Analyses of biomolecules for biodiversity, phylogeny or structure/function studies often use graphical tree representations. Many powerful tree editors are now available, but existing tree visualization tools make little use of meta-information related to the entities under study such as taxonomic descriptions or gene functions that can hardly be encoded within the tree itself (if using popular tree formats). Consequently, a tedious manual analysis and post-processing of the tree graphics are required if one needs to use external information for displaying or investigating trees. RESULTS: We have developed TreeDyn, a tool using annotations and dynamic graphical methods for editing and analyzing multiple trees. The main features of TreeDyn are 1) the management of multiple windows and multiple trees per window, 2) the export of graphics to several standard file formats with or without HTML encapsulation and a new format called TGF, which enables saving and restoring graphical analysis, 3) the projection of texts or symbols facing leaf labels or linked to nodes, through manual pasting or by using annotation files, 4) the highlight of graphical elements after querying leaf labels (or annotations) or by selection of graphical elements and information extraction, 5) the highlight of targeted trees according to a source tree browsed by the user, 6) powerful scripts for automating repetitive graphical tasks, 7) a command line interpreter enabling the use of TreeDyn through CGI scripts for online building of trees, 8) the inclusion of a library of packages dedicated to specific research fields involving trees. CONCLUSION: TreeDyn is a tree visualization and annotation tool which includes tools for tree manipulation and annotation and uses meta-information through dynamic graphical operators or scripting to help analyses and annotations of single trees or tree collections.

The pitfalls of proteomics experiments without the correct use of bioinformatics tools.

The elucidation of the entire genomic sequence of various organisms, from viruses to complex metazoans, most recently man, is undoubtedly the greatest triumph of molecular biology since the discovery of the DNA double helix. Over the past two decades, the focus of molecular biology has gradually moved from genomes to proteomes, the intention being to discover the functions of the genes themselves. The postgenomic era stimulated the development of new techniques (e.g. 2-DE and MS) and bioinformatics tools to identify the functions, reactions, interactions and location of the gene products in tissues and/or cells of living organisms. Both 2-DE and MS have been very successfully employed to identify proteins involved in biological phenomena (e.g. immunity, cancer, host-parasite interactions, etc.), although recently, several papers have emphasised the pitfalls of 2-DE experiments, especially in relation to experimental design, poor statistical treatment and the high rate of 'false positive' results with regard to protein identification. In the light of these perceived problems, we review the advantages and misuses of bioinformatics tools - from realisation of 2-DE gels to the identification of candidate protein spots - and suggest some useful avenues to improve the quality of 2-DE experiments. In addition, we present key steps which, in our view, need to be to taken into consideration during such analyses. Lastly, we present novel biological entities named 'interactomes', and the bioinformatics tools developed to analyse the large protein-protein interaction networks they form, along with several new perspectives of the field.

PRODISTIN Web Site: a tool for the functional classification of proteins from interaction networks.

UNLABELLED: The PRODISTIN Web Site is a web service allowing users to functionally classify genes/proteins from any type of interaction network. The resulting computation provides a classification tree in which (1) genes/proteins are clustered according to the identity of their interaction partners and (2) functional classes are delineated in the tree using the Biological Process Gene Ontology annotations. AVAILABILITY: The PRODISTIN Web Site is freely accessible at http://gin.univ-mrs.fr/webdistin

Physical and partial genetic map of Spodoptera frugiperda nucleopolyhedrovirus (SfMNPV) genome.

A Nicaraguan isolate of Spodoptera frugiperda multicapsid nucleopolyhedrovirus (SfMNPV) is undergoing field trials for control of this pest in the Americas. This isolate is composed of multiple genotypes, some of which are deletion mutants. Identification of the genetic changes in deleted genotypes cannot be accomplished without the construction of a detailed physical map. In the present study, combinations of restriction endonuclease analysis and Southern blot analysis was performed. This map was refined by sequencing the termini of cloned restriction fragments. The SfMNPV genome was estimated to be 129.3 kb, 8 kb larger than the previously characterized Sf-2 variant from the United States, due to a deletion between 14.8 and 21.0 m.u. in the physical map described in this study. A total of 27.92 kb were sequenced, which represented 21.5% of the whole genome and included 38 ORFs. Comparison with other sequenced baculoviruses revealed that SfMNPV displayed the highest sequence identity (66%) and gene arrangement (78%) with Spodoptera exigua MNPV, sharing 36 putative ORFs. In addition, the genome organization was similar to that of SeMNPV, with minor differences. Phylogenetic analysis confirmed the close relatedness between SeMNPV and SfMNPV, suggesting they evolved from a common ancestor.

Functional classification of proteins for the prediction of cellular function from a protein-protein interaction network.

We here describe PRODISTIN, a new computational method allowing the functional clustering of proteins on the basis of protein-protein interaction data. This method, assessed biologically and statistically, enabled us to classify 11% of the Saccharomyces cerevisiae proteome into several groups, the majority of which contained proteins involved in the same biological process(es), and to predict a cellular function for many otherwise uncharacterized proteins.