TaxonGap: a visualization tool for intra- and inter-species variation among individual biomarkers

Summary: Selection of optimal biomarkers for the identificationof different operational taxonomic units (OTUs) may be a hardand tedious task, especially when phylogenetic trees for multiplegenes need to be compared. With TaxonGap we present a noveland easy-to-handle software tool that allows visual comparisonof the discriminative power of multiple biomarkers for a setof OTUs. The compact graphical output allows for easy comparisonand selection of individual biomarkers. Availability: Graphical User Interface; Executable JAVA archivefile, source code, supplementary information and sample filescan be downloaded from the website: http://www.kermit.ugent.be/taxongap Contact: Bram.Slabbinck{at}UGent.be Associate Editor: John Quackenbush     

Interactive visualization software for exploring phylogenetic trees and clades

Summary: The Summary Tree Explorer (STE) is a Java applicationfor interactively exploring sets of phylogenetic trees usingtwo coupled representations: a node-and-link diagram and a textuallist of common clades. Selection, pruning, filtering or re-rootingin one representation is immediately reflected in the other.While summary trees are more effective at showing the relationshipamong clades, they can only show a consistent subset of thosethat appear in the textual list. Working with both representationsmitigates the disadvantages of having to choose just one. Availability: STE, along with several sample datasets, is availableat http://cityscape.inf.cs.cmu.edu/phylogeny/ Contact: mad{at}cs.cmu.edu Associate Editor: Martin Bishop     

PCCA: a program for phylogenetic canonical correlation analysis

Summary: PCCA (phylogenetic canonical correlation analysis)is a new program for canonical correlation analysis of multivariate,continuously valued data from biological species. Canonicalcorrelation analysis is a technique in which derived variablesare obtained from two sets of original variables whereby thecorrelations between corresponding derived variables are maximized.It is a very useful multivariate statistical method for thecalculation and analysis of correlations between character sets.The program controls for species non-independence due to phylogenetichistory and computes canonical coefficients, correlations andscores; and conducts hypothesis tests on the canonical correlations.It can also compute a multivariate version of Pagel's , whichcan then be used in the phylogenetic transformation. Availability: PCCA is distributed as DOS/Windows, Mac OS X andLinux/Unix executables with a detailed program manual and isfreely available on the World Wide Web at: http://anolis.oeb.harvard.edu/~liam/programs/. Contact: lrevell{at}fas.harvard.edu Associate Editor: Keith Crandall     

DNAPlotter: circular and linear interactive genome visualization

Summary: DNAPlotter is an interactive Java application for generatingcircular and linear representations of genomes. Making use ofthe Artemis libraries to provide a user-friendly method of loadingin sequence files (EMBL, GenBank, GFF) as well as data fromrelational databases, it filters features of interest to displayon separate user-definable tracks. It can be used to producepublication quality images for papers or web pages. Availability: DNAPlotter is freely available (under a GPL licence)for download (for MacOSX, UNIX and Windows) at the WellcomeTrust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/circular/ Contact: artemis{at}sanger.ac.uk Associate Editor: John Quackenbush     

PlasmoGF: an integrated system for comparative genomics and phylogenetic analysis of Plasmodium gene families

Summary: Malaria, one of the world's most common diseases, iscaused by the intracellular protozoan parasite known as Plasmodium.Recently, with the arrival of several malaria parasite genomes,we established an integrated system named PlasmoGF for comparativegenomics and phylogenetic analysis of Plasmodium gene families.Gene families were clustered using the Markov Cluster algorithmimplemented in TribeMCL program and could be searched usingkeywords, gene-family information, domain composition, GeneOntology and BLAST. Moreover, a number of useful bioinformaticstools were implemented to facilitate the analysis of these putativePlasmodium gene families, including gene retrieval, annotation,sequence alignment, phylogeny construction and visualization.In the current version, PlasmoGF contained 8980 sets of genefamilies derived from six malaria parasite genomes: Plasmodium.falciparum, P. berghei, P. knowlesi, P. chabaudi, P. vivax andP. yoelii. The availability of such a highly integrated systemwould be of great interest for the community of researchersworking on malaria parasite phylogenomics. Availability: PlasmoGF is freely available at http://bioinformatics.zj.cn/pgf/ Contact: xiaokunli{at}163.net; baoqy{at}genomics.org.cn; fuz3{at}psu.edu Associate Editor: Jonathan Wren The authors wish it to be known that, in their opinion, thefirst two authors should be regarded as joint First Authors.     

ROBIN: a tool for genome rearrangement of block-interchanges

Summary: ROBIN is a web server for analyzing genome rearrangementof block-interchanges between two chromosomal genomes. It takestwo or more linear/circular chromosomes as its input, and computesthe number of minimum block-interchange rearrangements betweenany two input chromosomes for transforming one chromosome intoanother and also determines an optimal scenario taking thisnumber of rearrangements. The input can be either bacterial-sizesequence data or landmark-order data. If the input is sequencedata, ROBIN will automatically search for the identical landmarksthat are the homologous/conserved regions shared by all theinput sequences. Availability: ROBIN is freely accessed at http://genome.life.nctu.edu.tw/ROBIN Contact: cllu{at}mail.nctu.edu.tw     

TOPALi v2: a rich graphical interface for evolutionary analyses of multiple alignments on HPC clusters and multi-core desktops

Summary: TOPALi v2 simplifies and automates the use of severalmethods for the evolutionary analysis of multiple sequence alignments.Jobs are submitted from a Java graphical user interface as TOPALiweb services to either run remotely on high-performance computingclusters or locally (with multiple cores supported). Methodsavailable include model selection and phylogenetic tree estimationusing the Bayesian inference and maximum likelihood (ML) approaches,in addition to recombination detection methods. The optimalsubstitution model can be selected for protein or nucleic acid(standard, or protein-coding using a codon position model) datausing accurate statistical criteria derived from ML co-estimationof the tree and the substitution model. Phylogenetic softwareavailable includes PhyML, RAxML and MrBayes. Availability: Freely downloadable from http://www.topali.orgfor Windows, Mac OS X, Linux and Solaris. Contact: iain.milne{at}scri.ac.uk Associate Editor: Martin Bishop     

Mining SARS-CoV protease cleavage data using non-orthogonal decision trees: a novel method for decisive template selection

Motivation: Although the outbreak of the severe acute respiratorysyndrome (SARS) is currently over, it is expected that it willreturn to attack human beings. A critical challenge to scientistsfrom various disciplines worldwide is to study the specificityof cleavage activity of SARS-related coronavirus (SARS-CoV)and use the knowledge obtained from the study for effectiveinhibitor design to fight the disease. The most commonly usedinductive programming methods for knowledge discovery from dataassume that the elements of input patterns are orthogonal toeach other. Suppose a sub-sequence is denoted as P₂P₁P_1'P_2',the conventional inductive programming method may result ina rule like ‘if P₁ = Q, then the sub-sequence is cleaved,otherwise non-cleaved’. If the site P₁ is not orthogonalto the others (for instance, P₂, P_1' and P_2'), the predictionpower of these kind of rules may be limited. Therefore thisstudy is aimed at developing a novel method for constructingnon-orthogonal decision trees for mining protease data. Result: Eighteen sequences of coronavirus polyprotein were downloadedfrom NCBI (http://www.ncbi.nlm.nih.gov). Among these sequences,252 cleavage sites were experimentally determined. These sequenceswere scanned using a sliding window with size k to generateabout 50 000 k-mer sub-sequences (for short, k-mers). The valueof k varies from 4 to 12 with a gap of two. The bio-basis functionproposed by Thomson et al. is used to transform the k-mers toa high-dimensional numerical space on which an inductive programmingmethod is applied for the purpose of deriving a decision treefor decision-making. The process of this transform is referredto as a bio-mapping. The constructed decision trees select about10 out of 50 000 k-mers. This small set of selected k-mers isregarded as a set of decisive templates. By doing so, non-orthogonaldecision trees are constructed using the selected templatesand the prediction accuracy is significantly improved. Availability: The program for bio-mapping can be obtained byrequest to the author. Contact: z.r.yang{at}exeter.ac.uk     

EMBL sequence submission system--an object-oriented approach to developing interactive data collection systems through the WWW

Motivation: To enable a new way of submitting sequence informationto the EMBL nucleotide database through the WWW. This processof data submission is long and complex, and calls for efficientand user-friendly mechanisms for collection and validation ofinformation. Results: Described here is a generic, object-oriented data-submissionsystem that is being used for the EMBL database, but can easilybe tailored to serve several data-submission schemes with arelatively short development and implementation time. The programprovides the user with a friendly interface that breaks thecomplex task into smaller, more manageable tasks and, on theother hand, acts as a pre-filter, scanning errors online. Availability: The program is accessible through the EMBL-EBlWWW server at the URL: http: //www.ebi.ac.uk/subs/ emblsubs.html Contact: E-mail: bshomer{at}ebi.ac.uk     

Special Care Is Needed in Applying Phylogenetic Comparative Methods to Gene Trees with Speciation and Duplication Nodes

How gene function evolves is a central question of evolutionary biology. It can be investigated by comparing functional genomics results between species and between genes. Most comparative studies of functional genomics have used pairwise comparisons. Yet it has been shown that this can provide biased results, as genes, like species, are phylogenetically related. Phylogenetic comparative methods should be used to correct for this, but they depend on strong assumptions, including unbiased tree estimates relative to the hypothesis being tested. Such methods have recently been used to test the “ortholog conjecture,” the hypothesis that functional evolution is faster in paralogs than in orthologs. Although pairwise comparisons of tissue specificity (τ) provided support for the ortholog conjecture, phylogenetic independent contrasts did not. Our reanalysis on the same gene trees identified problems with the time calibration of duplication nodes. We find that the gene trees used suffer from important biases, due to the inclusion of trees with no duplication nodes, to the relative age of speciations and duplications, to systematic differences in branch lengths, and to non-Brownian motion of tissue specificity on many trees. We find that incorrect implementation of phylogenetic method in empirical gene trees with duplications can be problematic. Controlling for biases allows successful use of phylogenetic methods to study the evolution of gene function and provides some support for the ortholog conjecture using three different phylogenetic approaches.     

Using flowViz to visualize flow cytometry data

Summary: Automated analysis of flow cytometry (FCM) data isessential for it to become successful as a high throughput technology.We believe that the principles of Trellis graphics can be adaptedto provide useful visualizations that can aid such automation.In this article, we describe the R/Bioconductor package flowVizthat implements such visualizations. Availability: flowViz is available as an R package from theBioconductor project: http://bioconductor.org Contact: dsarkar{at}fhcrc.org Associate Editor: Olga Troyanskaya     

Molecular Phylogenetic Characterization of Streptomyces Protease Inhibitor Family

We previously found that proteinaceous protease inhibitors homologous to Streptomyces subtilisin inhibitor (SSI) are widely produced by various Streptomyces species, and we designated them ``SSI-like proteins' (Taguchi S, Kikuchi H, Suzuki M, Kojima S, Terabe M, Miura K, Nakase T, Momose H [1993] Appl Environ Microbiol 59:4338–4341). In this study, SSI-like proteins from five strains of the genus Streptoverticillium were purified and sequenced, and molecular phylogenetic trees were constructed on the basis of the determined amino acid sequences together with those determined previously for Streptomyces species. The phylogenetic trees showed that SSI-like proteins from Streptoverticillium species are phylogenetically included in Streptomyces SSI-like proteins but form a monophyletic group as a distinct lineage within the Streptomyces proteins. This provides an alternative phylogenetic framework to the previous one based on partial small ribosomal RNA sequences, and it may indicate that the phylogenetic affiliation of the genus Streptoverticillium should be revised. The phylogenetic trees also suggested that SSI-like proteins possessing arginine or methionine at the P1 site, the major reactive center site toward target proteases, arose multiple times on independent lineages from ancestral proteins possessing lysine at the P1 site. Most of the codon changes at the P1 site inferred to have occurred during the evolution of SSI-like proteins are consistent with those inferred from the extremely high G + C content of Streptomyces genomes. The inferred minimum number of amino acid replacements at the P1 site was nearly equal to the average number for all the variable sites. It thus appears that positive Darwinian selection, which has been postulated to account for accelerated rates of amino acid replacement at the major reaction center site of mammalian protease inhibitors, may not have dictated the evolution of the bacterial SSI-like proteins. Received: 23 August 1996 / Accepted: 20 November 1996     

Quantitative quality-assessment techniques to compare fractionation and depletion methods in SELDI-TOF mass spectrometry experiments

Motivation: Mass spectrometry (MS), such as the surface-enhancedlaser desorption and ionization time-of-flight (SELDI-TOF) MS,provides a potentially promising proteomic technology for biomarkerdiscovery. An important matter for such a technology to be usedroutinely is its reproducibility. It is of significant interestto develop quantitative measures to evaluate the quality andreliability of different experimental methods. Results: We compare the quality of SELDI-TOF MS data using unfractionated,fractionated plasma samples and abundant protein depletion methodsin terms of the numbers of detected peaks and reliability. Severalstatistical quality-control and quality-assessment techniquesare proposed, including the Graeco–Latin square designfor the sample allocation on a Protein chip, the use of thepairwise Pearson correlation coefficient as the similarity measurebetween the spectra in conjunction with multi-dimensional scaling(MDS) for graphically evaluating similarity of replicates andassessing outlier samples; and the use of the reliability ratiofor evaluating reproducibility. Our results show that the numberof peaks detected is similar among the three sample preparationtechnologies, and the use of the Sigma multi-removal kit doesnot improve peak detection. Fractionation of plasma samplesintroduces more experimental variability. The peaks detectedusing the unfractionated plasma samples have the highest reproducibilityas determined by the reliability ratio. Availability: Our algorithm for assessment of SELDI-TOF experimentquality is available at http://www.biostat.harvard.edu/~xlin Contact: harezlak{at}post.harvard.edu Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Thomas Lengauer     

GOTreePlus: an interactive gene ontology browser

Summary: We developed an interactive gene ontology (GO) browsernamed GOTreePlus that superimposes annotation information overGO structures. It can facilitate the identification of importantGO terms through interactive visualization of them in the GOstructure. The interactive pie chart summarizing an annotationdistribution for a selected GO term provides users with a succinctcontext-sensitive overview of their experimental results. Wetested our GOTreePlus using a proteome profiling dataset obtainedon differentiation of retinal pigment epithelial cells where399 proteins were quantified. Availability: http://bioinformatics.cnmcresearch.org/GOTreePlus/ Contact: jseo{at}cnmcresearch.org Associate Editor: John Quackenbush     

ISD: a software package for Bayesian NMR structure calculation

Summary: The conventional approach to calculating biomolecularstructures from nuclear magnetic resonance (NMR) data is oftenviewed as subjective due to its dependence on rules of thumbfor deriving geometric constraints and suitable values for theoryparameters from noisy experimental data. As a result, it canbe difficult to judge the precision of an NMR structure in anobjective manner. The inferential Structure determination (ISD)framework, which has been introduced recently, addresses thisproblem by using Bayesian inference to derive a probabilitydistribution that represents both the unknown structure andits uncertainty. It also determines additional unknowns, suchas theory parameters, that normally need to be chosen empirically.Here we give an overview of the ISD software package, whichimplements this methodology. Availability: http://www.bioc.cam.ac.uk/isd Contact: wolfgang.rieping{at}bioc.cam.ac.uk, michael.habeck{at}tuebingen.mpg.de Associate Editor: Alfonso Valencia