JAE

One of the most basic methods of understanding the biological significance of a sequence is to produce an alignment with related sequences. A vital aspect of correctly aligning sequences is to apply biological intuition through manual editing of an alignment produced by multiple-sequence alignment software. As part of the European Molecular Biology Open Source Software Suite (EMBOSS), a new alignment editor in the Jemboss package is freely available for download. The Jemboss Alignment Editor (JAE) incorporates standard methods of editing, and colouring residues and nucleotides to highlight important regions of interest. JAE also makes use of scoring matrices (PAM and BLOSUM), selected by the user, to display regions of high degrees of similarity and identity. Other tools include the ability to calculate a consensus, a consensus plot (using a selected scoring matrix) and pairwise identities. AVAILABILITY: The JAE can be launched from the webpage (http://emboss.sourceforge.net/Jemboss/).     

T(E)Xtopo: shaded membrane protein topology plots in LAT(E)X2epsilon

SUMMARY: T(E)Xtopo is a LAT(E)X2epsilon macro package for plotting topology data directly from PHD predictions or SwissProt database files in publication-ready quality. The plot can be shaded automatically to emphasize conserved residues or functional properties of the residue sidechains. The addition of rich decorations, such as labels, annotations and legends, is easily accomplished. AVAILABILITY: The T(E)Xtopo macro package and a full on-line documentation are freely available at http://homepages.uni-tuebingen.de/beitz/ CONTACT: eric.beitz@uni-tuebingen.de     

SQUINT: a multiple alignment program and editor

SUMMARY: SQUINT is a sequence alignment tool, and combines both automated progressive sequence alignment with facilities for manual editing. The program imports nucleotide or amino acid sequence multiple alignment files in standard formats, and permits users to view two translations of the same multiple alignment simultaneously. Edits in one view are instantaneously reflected in the other, and the scoring cost of the changes are shown in real-time. Progressive multiple alignments, using a variety of alignment parameters, can be performed on any block of sequences, including blocks embedded in the existing alignment. AVAILABILITY: The software is freely available for download at http://www.cebl.auckland.ac.nz     

Genquire: genome annotation browser/editor

We present a software package, Genquire, that allows visualization, querying, hand editing, and de novo markup of complete or partially annotated genomes. The system is written in Perl/Tk and uses, where possible, existing BioPerl data models and methods for representation and manipulation of the sequence and annotation objects. An adaptor API is provided to allow Genquire to display a wide range of databases and flat files, and a plugins API provides an interface to other sequence analysis software. AVAILABILITY: Genquire v3.03 is open-source software. The code is available for download and/or contribution at http://www.bioinformatics.org/Genquire     

snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium plotting package

snp.plotter is a newly developed R package which produces high-quality plots of results from genetic association studies. The main features of the package include options to display a linkage disequilibrium (LD) plot below the P-value plot using either the r2 or D' LD metric, to set the X-axis to equal spacing or to use the physical map of markers, and to specify plot labels, colors, symbols and LD heatmap color scheme. snp.plotter can plot single SNP and/or haplotype data and simultaneously plot multiple sets of results. R is a free software environment for statistical computing and graphics available for most platforms. The proposed package provides a simple way to convey both association and LD information in a single appealing graphic for genetic association studies. AVAILABILITY: Downloadable R package and example datasets are available at http://cbdb.nimh.nih.gov/~kristin/snp.plotter.html and http://www.r-project.org.     

TM-MOTIF: an alignment viewer to annotate predicted transmembrane helices and conserved motifs in aligned set of sequences

Multiple sequence alignments become biologically meaningful only if conserved and functionally important residues and secondary structural elements preserved can be identified at equivalent positions. This is particularly important for transmembrane proteins like G-protein coupled receptors (GPCRs) with seven transmembrane helices. TM-MOTIF is a software package and an effective alignment viewer to identify and display conserved motifs and amino acid substitutions (AAS) at each position of the aligned set of homologous sequences of GPCRs. The key feature of the package is to display the predicted membrane topology for seven transmembrane helices in seven colours (VIBGYOR colouring scheme) and to map the identified motifs on its respective helices /loop regions. It is an interactive package which provides options to the user to submit query or pre-aligned set of GPCR sequences to align with a reference sequence, like rhodopsin, whose structure has been solved experimentally. It also provides the possibility to identify the nearest homologue from the available inbuilt GPCR or Olfactory Receptor cluster dataset whose association is already known for its receptor type. AVAILABILITY: The database is available for free at mini@ncbs.res.in.     

VisRD--visual recombination detection

SUMMARY: VisRD, a program for visual recombination detection in a sequence alignment is presented. VisRD is written in Java and is designed to complement the multi-purpose phylogenetic software package SplitsTree4. AVAILABILITY: The software is freely available from http://www.lcb.uu.se/~vmoulton/software/visrd/     

DIDA: Distributed Indexing Dispatched Alignment

One essential application in bioinformatics that is affected by the high-throughput sequencing data deluge is the sequence alignment problem, where nucleotide or amino acid sequences are queried against targets to find regions of close similarity. When queries are too many and/or targets are too large, the alignment process becomes computationally challenging. This is usually addressed by preprocessing techniques, where the queries and/or targets are indexed for easy access while searching for matches. When the target is static, such as in an established reference genome, the cost of indexing is amortized by reusing the generated index. However, when the targets are non-static, such as contigs in the intermediate steps of a de novo assembly process, a new index must be computed for each run. To address such scalability problems, we present DIDA, a novel framework that distributes the indexing and alignment tasks into smaller subtasks over a cluster of compute nodes. It provides a workflow beyond the common practice of embarrassingly parallel implementations. DIDA is a cost-effective, scalable and modular framework for the sequence alignment problem in terms of memory usage and runtime. It can be employed in large-scale alignments to draft genomes and intermediate stages of de novo assembly runs. The DIDA source code, sample files and user manual are available through http://www.bcgsc.ca/platform/bioinfo/software/dida. The software is released under the British Columbia Cancer Agency License (BCCA), and is free for academic use.     

TOPALi: software for automatic identification of recombinant sequences within DNA multiple alignments

SUMMARY: TOPALi is a new Java graphical analysis application that allows the user to identify recombinant sequences within a DNA multiple alignment (either automatically or via manual investigation). TOPALi allows a choice of three statistical methods to predict the positions of breakpoints due to past recombination. The breakpoint predictions are then used to identify putative recombinant sequences and their relationships to other sequences. In addition to its sophisticated interface, TOPALi can import many sequence formats, estimate and display phylogenetic trees and allow interactive analysis and/or automatic HTML report generation. AVAILABILITY: TOPALi is freely available from http://www.bioss.ac.uk/software.html     

PartTree: an algorithm to build an approximate tree from a large number of unaligned sequences

MOTIVATION: To construct a multiple sequence alignment (MSA) of a large number (> approximately 10,000) of sequences, the calculation of a guide tree with a complexity of O(N2) to O(N3), where N is the number of sequences, is the most time-consuming process. RESULTS: To overcome this limitation, we have developed an approximate algorithm, PartTree, to construct a guide tree with an average time complexity of O(N log N). The new MSA method with the PartTree algorithm can align approximately 60,000 sequences in several minutes on a standard desktop computer. The loss of accuracy in MSA caused by this approximation was estimated to be several percent in benchmark tests using Pfam. AVAILABILITY: The present algorithm has been implemented in the MAFFT sequence alignment package (http://align.bmr.kyushu-u.ac.jp/mafft/software/). SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.     

DNAAlignEditor: DNA alignment editor tool

Background

With advances in DNA re-sequencing methods and Next-Generation parallel sequencing approaches, there has been a large increase in genomic efforts to define and analyze the sequence variability present among individuals within a species. For very polymorphic species such as maize, this has lead to a need for intuitive, user-friendly software that aids the biologist, often with naïve programming capability, in tracking, editing, displaying, and exporting multiple individual sequence alignments. To fill this need we have developed a novel DNA alignment editor.

Results

We have generated a nucleotide sequence alignment editor (DNAAlignEditor) that provides an intuitive, user-friendly interface for manual editing of multiple sequence alignments with functions for input, editing, and output of sequence alignments. The color-coding of nucleotide identity and the display of associated quality score aids in the manual alignment editing process. DNAAlignEditor works as a client/server tool having two main components: a relational database that collects the processed alignments and a user interface connected to database through universal data access connectivity drivers. DNAAlignEditor can be used either as a stand-alone application or as a network application with multiple users concurrently connected.

Conclusion

We anticipate that this software will be of general interest to biologists and population genetics in editing DNA sequence alignments and analyzing natural sequence variation regardless of species, and will be particularly useful for manual alignment editing of sequences in species with high levels of polymorphism.

     

JIGSAW: integration of multiple sources of evidence for gene prediction

MOTIVATION: Computational gene finding systems play an important role in finding new human genes, although no systems are yet accurate enough to predict all or even most protein-coding regions perfectly. Ab initio programs can be augmented by evidence such as expression data or protein sequence homology, which improves their performance. The amount of such evidence continues to grow, but computational methods continue to have difficulty predicting genes when the evidence is conflicting or incomplete. Genome annotation pipelines collect a variety of types of evidence about gene structure and synthesize the results, which can then be refined further through manual, expert curation of gene models. RESULTS: JIGSAW is a new gene finding system designed to automate the process of predicting gene structure from multiple sources of evidence, with results that often match the performance of human curators. JIGSAW computes the relative weight of different lines of evidence using statistics generated from a training set, and then combines the evidence using dynamic programming. Our results show that JIGSAW's performance is superior to ab initio gene finding methods and to other pipelines such as Ensembl. Even without evidence from alignment to known genes, JIGSAW can substantially improve gene prediction accuracy as compared with existing methods. AVAILABILITY: JIGSAW is available as an open source software package at http://cbcb.umd.edu/software/jigsaw.     

LocARNA-P: accurate boundary prediction and improved detection of structural RNAs

Current genomic screens for noncoding RNAs (ncRNAs) predict a large number of genomic regions containing potential structural ncRNAs. The analysis of these data requires highly accurate prediction of ncRNA boundaries and discrimination of promising candidate ncRNAs from weak predictions. Existing methods struggle with these goals because they rely on sequence-based multiple sequence alignments, which regularly misalign RNA structure and therefore do not support identification of structural similarities. To overcome this limitation, we compute columnwise and global reliabilities of alignments based on sequence and structure similarity; we refer to these structure-based alignment reliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely used ncRNA gene finder RNAz by a factor of 3 from a median deviation of 47 to 13 nt. Post-processing RNAz predictions, LocARNA-P's STAR score allows much stronger discrimination between true- and false-positive predictions than RNAz's own evaluation. The improved accuracy, in this scenario increased from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for LocARNA/LocARNA-P, and the software package, including documentation and a pipeline for refining screens for structural ncRNA, at http://www.bioinf.uni-freiburg.de/Supplements/LocARNA-P/.     

SITEBLAST--rapid and sensitive local alignment of genomic sequences employing motif anchors

MOTIVATION: Comparative sequence analysis is the essence of many approaches to genome annotation. Heuristic alignment algorithms utilize similar seed pairs to anchor an alignment. Some applications of local alignment algorithms (e.g. phylogenetic footprinting) would benefit from including prior knowledge (e.g. binding site motifs) in the alignment building process. RESULTS: We introduce predefined sequence patterns as anchor points into a heuristic local alignment strategy. We extended the BLASTZ program for this purpose. A set of seed patterns is either given as consensus sequences in IUPAC code or position-weight-matrices. Phylogenetic footprinting of promoter regions is one of many potential applications for the SITEBLAST software. AVAILABILITY: The source code is freely available to the academic community from http://corg.molgen.mpg.de/software     

The iRMSD: a local measure of sequence alignment accuracy using structural information

MOTIVATION: We introduce the iRMSD, a new type of RMSD, independent from any structure superposition and suitable for evaluating sequence alignments of proteins with known structures. RESULTS: We demonstrate that the iRMSD is equivalent to the standard RMSD although much simpler to compute and we also show that it is suitable for comparing sequence alignments and benchmarking multiple sequence alignment methods. We tested the iRMSD score on 6 established multiple sequence alignment packages and found the results to be consistent with those obtained using an established reference alignment collection like Prefab. AVAILABILITY: The iRMSD is part of the T-Coffee package and is distributed as an open source freeware (http://www.tcoffee.org/).     

BADASP: predicting functional specificity in protein families using ancestral sequences

SUMMARY: Burst After Duplication with Ancestral Sequence Predictions (BADASP) is a software package for identifying sites that may confer subfamily-specific biological functions in protein families following functional divergence of duplicated proteins. A given protein phylogeny is grouped into subfamilies based on orthology/paralogy relationships and/or user definitions. Ancestral sequences are then predicted from the sequence alignment and the functional specificity is calculated using variants of the Burst After Duplication method, which tests for radical amino acid substitutions following gene duplications that are subsequently conserved. Statistics are output along with subfamily groupings and ancestral sequences for an easy analysis with other packages. AVAILABILITY: BADASP is freely available from http://www.bioinformatics.rcsi.ie/~redwards/badasp/     

CLUSTAL V: improved software for multiple sequence alignment

The CLUSTAL package of multiple sequence alignment programshas been completely rewritten and many new features added. Thenew software is a single program called CLUSTAL V, which iswritten in C and can be used on standard C compiler. The mainnew features are the ability to store and reuse old alignmentsand the ability to calculate phylogenetic trees after alignment.The program is simple to use, completely menu driven and on-linehelp is provided.     

A comprehensive package for DNA sequence analysis in FORTRAN IV for the PDP-11.

A computer package written in Fortran-IV for the PDP-11 minicomputer is described. The package's novel features are: software for voice-entry of sequence data; a less memory intensive algorithm for optimal sequence alignment; and programs that fit statistical models to nucleic acid and protein sequences.     

DNA Translator and Aligner: HyperCard Utilities to aid phylogenetic analysis of molecules

DNA Translator and Aligner are molecular phylogenetics HyperCardstacks for Macintosh computers. They manipulate sequence datato provide graphical gene mapping, conversions, translationsand manual multiple-sequence alignment editing. DNA Translatoris able to convert documented GenBank or EMBL documented sequencesinto linearized, rescalable gene maps whose gene sequences areextractable by clicking on the corresponding map button or byselection from a scrolling list. Provided gene maps, completewith extractable sequences, consist of nine metazoan, one yeast,and one ciliate mitochon-drial DNAs and three green plant chloroplastDNAs. Single or multiple sequences can be manipulated to aidin phylogenetic analysis. Sequences can be translated betweennucleic acids and proteins in either direction with flexiblesupport of alternate genetic codes and ambiguous nucleotidesymbols. Multiple aligned sequence output from diverse sourcescan be converted to Nexus, Hennig86 or PHYLIP format for subsequentphylogenetic analysis. Input or output alignments can be examinedwith Aligner, a convenient accessory stack included in the DNATranslator package. Aligner is an editor for the manual alignmentof up to 100 sequences that toggles between display of matchedcharacters and normal unmatched sequences. DNA Translator alsogenerates graphic displays of ammo acid coding and codon usagefrequency relative to all other, or only synonymous, codonsfor 70 select organism–organelle combinations. Codonusage data is compatible with spreadsheet or UWGCG formats forincorporation of additional molecules of interest. The completepackage is available via anonymous ftp and is free for non–commercialuses.