Debian Med Biology packages

Adun is a biomolecular simulator that also includes data management and analysis capabilities. It was developed at the Computational Biophysics and Biochemistry Laboratory, a part of the Research Unit on Biomedical Informatics of the UPF.

Alien_hunter is an application for the prediction of putative Horizontal Gene Transfer (HGT) events with the implementation of Interpolated Variable Order Motifs (IVOMs). An IVOM approach exploits compositional biases using variable order motif distributions and captures more reliably the local composition of a sequence compared to fixed-order methods. Optionally the predictions can be parsed into a 2-state 2nd order Hidden Markov Model (HMM), in a change-point detection framework, to optimize the localization of the boundaries of the predicted regions. The predictions (embl format) can be automatically loaded into Artemis genome viewer freely available at: http://www.sanger.ac.uk/Software/Artemis/.

The manuscript describing the alien_hunter algorithm is available from Bioinformatics: Interpolated variable order motifs for identification of horizontally acquired DNA: revisiting the Salmonella pathogenicity islands. Vernikos GS, Parkhill J Bioinformatics. 2006;. PMID: 16837528

ALTree was designed to perform phylogeny based analysis: first, it allows the detection of an association between a candidate gene and a disease, and second, it enables to make hypothesis about the susceptibility loci.

AMAP is a command line tool to perform multiple alignment of peptidic sequences. It utilizes posterior decoding, and a sequence-annealing alignment, instead of the traditional progressive alignment method. It is the only alignment program that allows to control the sensitivity / specificity tradeoff. It is based on the ProbCons source code, but uses alignment metric accuracy and eliminates the consistency transformation.

The java visualisation tool of AMAP 2.2 is not yet packaged in Debian.

AutoDock is a prime representative of the programs addressing the simulation of the docking of fairly small chemical ligands to rather big protein receptors. Earlier versions had all flexibility in the ligands while the protein was kept rather ridgid. This latest version 4 also allows for a flexibility of selected sidechains of surface residues, i.e., takes the rotamers into account.

The AutoDock program performs the docking of the ligand to a set of grids describing the target protein. AutoGrid pre-calculates these grids.

BALLView provides fast OpenGL-based visualization of molecular structures, molecular mechanics methods (minimization, MD simulation using the AMBER, CHARMM, and MMFF94 force fields), calculation and visualization of electrostatic properties (FDPB) and molecular editing features.

BALLView can be considered a graphical user interface on the basis of BALL (Biochemical Algorithms Library), having taken the most common demands of protein chemists and biophysicists in particular taken into account. which is currently being developed in the groups of Hans-Peter Lenhof (Saarland University, Saarbruecken, Germany) and Oliver Kohlbacher (University of Tuebingen, Germany). BALL is an application framework in C++ that has been specifically designed for rapid software development in Molecular Modeling and Computational Molecular Biology. It provides an extensive set of data structures as well as classes for Molecular Mechanics, advanced solvation methods, comparison and analysis of protein structures, file import/export, and visualization.

The famous sequence alignment program. This is "official" NCBI version, #2. The blastall executable allows you to give a nucleotide or protein sequence to the program. It is compared against databases and a summary of matches is returned to the user.

Note that databases are not included in Debian; they must be retrieved manually.

Boxshade is a program for creating good looking printouts from multiple-aligned protein or DNA sequences. The program does not perform the alignment by itself and requires as input a file that was created by a multiple alignment program or manually edited with respective tools.

Boxshade reads multiple-aligned sequences from either PILEUP-MSF, CLUSTAL-ALN, MALIGNED-data and ESEE-save files (limited to a maximum of 150 sequences with up to 10000 elements each). Various kinds of shading can be applied to identical/similar residues. Output is written to screen or to a file in the following formats: ANSI/VT100, PS/EPS, RTF, HPGL, ReGIS, LJ250-printer, ASCII, xFIG, PICT, HTML

Burrows-Wheeler Aligner (BWA) is a program that aligns relatively short nucleotide sequences against a long reference sequence such as the human genome. It implements two algorithms, bwa-short and BWA-SW. The former works for query sequences shorter than 200 bp and the latter for longer sequences up to around 100 kbp. Both algorithms do gapped alignment. They are usually more accurate and faster on queries with low error rates.

DIALIGN2 is a command line tool to perform multiple alignment of protein or DNA sequences. It constructs alignments from gapfree pairs of similar segments of the sequences. This scoring scheme for alignments is the basic difference between DIALIGN and other global or local alignment methods. Note that DIALIGN does not employ any kind of gap penalty. It has been published by Morgenstern B. in Bioinformatics. 1999 Mar;15(3):211-8.

DIALIGN-TX is a command line tool to perform multiple alignment of protein or DNA sequences. It is a complete reimplementation of the segment-base approach including several new improvements and heuristics that significantly enhance the quality of the output alignments compared to DIALIGN 2.2 and DIALIGN-T. For pairwise alignment, DIALIGN-TX uses a fragment-chaining algorithm that favours chains of low-scoring local alignments over isolated high-scoring fragments. For multiple alignment, DIALIGN-TX uses an improved greedy procedure that is less sensitive to spurious local sequence similarities.

DIALIGN-TX has been published in Amarendran R. Subramanian, Michael Kaufmann, Burkhard Morgenstern: Improvement of the segment-based approach for multiple sequence alignment by combining greedy and progressive alignment strategies, Algorithms for Molecular Biology 3:6, 2008

The DOMAINATRIX programs were developed by Jon Ison and colleagues at MRC HGMP for their protein domain research. They are included as an EMBASSY package as a work in progress.

Applications in the current domainatrix release are cathparse (generates DCF file from raw CATH files), domainnr (removes redundant domains from a DCF file), domainreso (removes low resolution domains from a DCF file), domainseqs (adds sequence records to a DCF file), domainsse (adds secondary structure records to a DCF file), scopparse (generates DCF file from raw SCOP files) and ssematch (searches a DCF file for secondary structure matches).

The DOMALIGN programs were developed by Jon Ison and colleagues at MRC HGMP for their protein domain research. They are included as an EMBASSY package as a work in progress.

Applications in the current domalign release are allversusall (sequence similarity data from all-versus-all comparison), domainalign (generates alignments (DAF file) for nodes in a DCF file), domainrep (reorders DCF file to identify representative structures) and seqalign (extend alignments (DAF file) with sequences (DHF file)).

The DOMSEARCH programs were developed by Jon Ison and colleagues at MRC HGMP for their protein domain research. They are included as an EMBASSY package as a work in progress.

Applications in this DOMSEARCH release are seqfraggle (removes fragment sequences from DHF files), seqnr (removes redundancy from DHF files), seqsearch (generates PSI-BLAST hits (DHF file) from a DAF file), seqsort (Remove ambiguous classified sequences from DHF files) and seqwords (Generates DHF files from keyword search of UniProt).

EMBOSS is a free Open Source software analysis package specially developed for the needs of the molecular biology (e.g. EMBnet) user community. The software automatically copes with data in a variety of formats and even allows transparent retrieval of sequence data from the web. Also, as extensive libraries are provided with the package, it is a platform to allow other scientists to develop and release software in true open source spirit. EMBOSS also integrates a range of currently available packages and tools for sequence analysis into a seamless whole. EMBOSS breaks the historical trend towards commercial software packages.

Exonerate allows you to align sequences using a many alignment models, using either exhaustive dynamic programming, or a variety of heuristics. Much of the functionality of the Wise dynamic programming suite was reimplemented in C for better efficiency. Exonerate is an intrinsic component of the building of the Ensembl genome databases, providing similarity scores between RNA and DNA sequences and thus determining splice variants and coding sequences in general.

An In-silico PCR Experiment Simulation System (see the ipcress man page) is packaged with exonerate.

This package also comes with a selection of utilities for performing simple manipulations quickly on fasta files beyond 2Gb

fastDNAml is a program derived from Joseph Felsenstein's version 3.3 DNAML (part of his PHYLIP package). Users should consult the documentation for DNAML before using this program.

fastDNAml is an attempt to solve the same problem as DNAML, but to do so faster and using less memory, so that larger trees and/or more bootstrap replicates become tractable. Much of fastDNAml is merely a recoding of the PHYLIP 3.3 DNAML program from PASCAL to C.

Note that the homepage of this program is not available any more and so this program will probably not see any further updates.

Genetic linkage analysis is a statistical technique used to map genes and find the approximate location of disease genes. There was a standard software package for genetic linkage called LINKAGE. FASTLINK is a significantly modified and improved version of the main programs of LINKAGE that runs much faster sequentially, can run in parallel, allows the user to recover gracefully from a computer crash, and provides abundant new documentation. FASTLINK has been used in over 1000 published genetic linkage studies.

This package contains the following programs:

 ilink:    GEMINI optimization procedure to find a locally
           optimal value of the theta vector of recombination
           fractions
 linkmap:  calculates location scores of one locus against a
           fixed map of other loci
 lodscore: compares likelihoods at locally optimal theta
 mlink:    calculates lod scores and risk with two of more loci
 unknown:  identify possible genotypes for unknowns

GAMGI provides a graphic interface to build and analyse atomic structures. The program is aimed at the scientific community, who needs a graphic interface to study atomic structures and to prepare images for presentations, and for teaching the atomic structure of matter.

Garlic is written for the investigation of membrane proteins. It may be used to visualize other proteins, as well as some geometric objects. This version of garlic recognizes PDB format version 2.1. Garlic may also be used to analyze protein sequences.

It only depends on the X libraries, no other libraries are needed.

Features include:

• The slab position and thickness are visible in a small window.
• Atomic bonds as well as atoms are treated as independent drawable objects.
• The atomic and bond colors depend on position. Five mapping modes are available (as for slab).
• Capable to display stereo image.
• Capable to display other geometric objects, like membrane.
• Atomic information is available for atom covered by the mouse pointer. No click required, just move the mouse pointer over the structure!
• Capable to load more than one structure.
• Capable to draw Ramachandran plot, helical wheel, Venn diagram, averaged hydrophobicity and hydrophobic moment plot.
• The command prompt is available at the bottom of the main window. It is able to display one error message and one command string.

gpdc is a graphical program for visualising output data from molecular dynamics simulations. It reads input in the standard xyz format, as well as other custom formats, and can output pictures of each frame in JPG or PNG format.

A program to visualize the alignment of two genomic sequences together with their annotations. From GFF-format input files it produces PostScript figures for that alignment. The following menu lists many features of gff2aplot:

• Comprehensive alignment plots for any GFF-feature. Attributes are defined separately so you can modify only whatsoever attributes for a given file or share same customization across different data-sets.
• All parameters are set by default within the program, but it can be also fully configured via gff2ps-like flexible customization files. Program can handle several of such files, summarizing all the settings before producing the corresponding figure. Moreover, all customization parameters can be set via command-line switches, which allows users to play with those parameters before adding any to a customization file.
• Source order is taken from input files, if you swap file order you can visualize alignment and its annotation with the new input arrangement.
• All alignment scores can be visualized in a PiP box below gff2aplot area, using grey-color scale, user-defined color scale or score-dependent gradients.
• Scalable fonts, which can also be chosen among the basic PostScript default fonts. Feature and group labels can be rotated to improve readability in both annotation axes.
• The program is still defined as a Unix filter so it can handle data from files, redirections and pipes, writing output to standard-output and warnings to standard error.
• gff2aplot is able to manage many physical page formats (from A0 to A10, and more -see available page sizes in its manual-), including user-defined ones. This allows, for instance, the generation of poster size genomic maps, or the use of a continuous-paper supporting plotting device, either in portrait or landscape.
• You can draw different alignments on same alignment plot and distinguish them by using different colors for each.
• Shape dictionary has been expanded, so that further feature shapes are now available (see manual).
• Annotation projections through alignment plots (so called ribbons) emulate transparencies via complementary color fill patterns. This feature allows to show color pseudo-blending when horizontal and vertical ribbons overlap.

gff2ps is a script program developed with the aim of converting gff-formatted records into high quality one-dimensional plots in PostScript. Such plots maybe useful for comparing genomic structures and to visualizing outputs from genome annotation programs. It can be used in a very simple way, because it assumes that the GFF file itself carries enough formatting information, but it also allows through a number of options and/or a configuration file, for a great degree of customization.

Ghemical is a computational chemistry software package written in C++. It has a graphical user interface and it supports both quantum- mechanics (semi-empirical) models and molecular mechanics models. Geometry optimization, molecular dynamics and a large set of visualization tools using OpenGL are currently available.

Ghemical relies on external code to provide the quantum-mechanical calculations. Semi-empirical methods MNDO, MINDO/3, AM1 and PM3 come from the MOPAC7 package (Public Domain), and are included in the package. The MPQC package is used to provide ab initio methods: the methods based on Hartree-Fock theory are currently supported with basis sets ranging from STO-3G to 6-31G.

GLAM2 is a software package for finding motifs in sequences, typically amino-acid or nucleotide sequences. A motif is a re-occurring sequence pattern: typical examples are the TATA box and the CAAX prenylation motif. The main innovation of GLAM2 is that it allows insertions and deletions in motifs.

The package includes these programs:

 glam2:       discovering motifs shared by a set of sequences;
 glam2scan:   finding matches, in a sequence database, to a motif discovered
              by glam2;
 glam2format: converting glam2 motifs to  standard alignment formats;
 glam2mask:   masking glam2 motifs out of sequences, so that weaker motifs
              can be found;
 glam2-purge: removing highly similar members of a set of sequences.

In this package, the fast Fourier algorithm (FFT) was enabled for glam2.

If you use GLAM2, please cite: MC Frith, NFW Saunders, B Kobe, TL Bailey (2008) Discovering sequence motifs with arbitrary insertions and deletions, PLoS Computational Biology (in press).

GROMACS is a versatile package to perform molecular dynamics, i.e. simulate the Newtonian equations of motion for systems with hundreds to millions of particles.

It is primarily designed for biochemical molecules like proteins and lipids that have a lot of complicated bonded interactions, but since GROMACS is extremely fast at calculating the nonbonded interactions (that usually dominate simulations) many groups are also using it for research on non- biological systems, e.g. polymers.

GROMACS offers entirely too many features for a brief description to do it justice. A more complete listing is available at http://www.gromacs.org/content/view/12/176/.

HMMER is an implementation of profile hidden Markov model methods for sensitive searches of biological sequence databases using multiple sequence alignments as queries.

Given a multiple sequence alignment as input, HMMER builds a statistical model called a "hidden Markov model" which can then be used as a query into a sequence database to find (and/or align) additional homologues of the sequence family.

Infernal ("INFERence of RNA ALignment") is for searching DNA sequence databases for RNA structure and sequence similarities. It is an implementation of a special case of profile stochastic context-free grammars called covariance models (CMs). A CM is like a sequence profile, but it scores a combination of sequence consensus and RNA secondary structure consensus, so in many cases, it is more capable of identifying RNA homologs that conserve their secondary structure more than their primary sequence.

The tool is an integral component of the Rfam database.

Kalign is a command line tool to perform multiple alignment of biological sequences. It employs the Muth-Manber string-matching algorithm, to improve both the accuracy and speed of the alignment. It uses global, progressive alignment approach, enriched by employing an approximate string-matching algorithm to calculate sequence distances and by incorporating local matches into the otherwise global alignment.

LAST is software for comparing and aligning sequences, typically DNA or protein sequences. LAST is similar to BLAST, but it copes better with very large amounts of sequence data. Here are two things LAST is good at:

• Comparing large (e.g. mammalian) genomes.
• Mapping lots of sequence tags onto a genome.

The main technical innovation is that LAST finds initial matches based on their multiplicity, instead of using a fixed size (e.g. BLAST uses 11-mers). This allows to map tags to genomes without repeat-masking, without becoming overwhelmed by repetitive hits. To find these variable-sized matches, it uses a suffix array (inspired by Vmatch). To achieve high sensitivity, it uses a discontiguous suffix array, analogous to spaced seeds.

Performs Markov chain Monte Carlo multipoint linkage analysis on large, complex pedigrees. The current package supports analyses on quantitative traits only, although this restriction will be lifted in later versions. Joint estimation of QTL number, position and effects uses Reversible Jump MCMC. It is also possible to perform affected only IBD sharing analyses.

The homepage of this project used to be at http://loki.homeunix.net but the project is dead now and the homepage vanished. The Homepage field above points to the web archive.

MAFFT is a multiple sequence alignment program which offers three accuracy-oriented methods:

• L-INS-i (probably most accurate; recommended for <200 sequences; iterative refinement method incorporating local pairwise alignment information),

• G-INS-i (suitable for sequences of similar lengths; recommended for <200 sequences; iterative refinement method incorporating global pairwise alignment information),

• E-INS-i (suitable for sequences containing large unalignable regions; recommended for <200 sequences), and five speed-oriented methods:

• FFT-NS-i (iterative refinement method; two cycles only),

• FFT-NS-i (iterative refinement method; max. 1000 iterations),

• FFT-NS-2 (fast; progressive method),

• FFT-NS-1 (very fast; recommended for >2000 sequences; progressive method with a rough guide tree),

• NW-NS-PartTree-1 (recommended for ∼50,000 sequences; progressive method with the PartTree algorithm).

Maq (short for Mapping and Assembly with Quality) builds mapping assemblies from short reads generated by the next-generation sequencing machines. It is particularly designed for Illumina-Solexa 1G Genetic Analyzer, and has a preliminary functionality to handle ABI SOLiD data. Maq is previously known as mapass2.

With Maq you can:

• Fast align Illumina/SOLiD reads to the reference genome. With the default options, one million pairs of reads can be mapped to the human genome in about 10 CPU hours with less than 1G memory.
• Accurately measure the error probability of the alignment of each individual read.
• Call the consensus genotypes, including homozygous and heterozygous polymorphisms, with a Phred probabilistic quality assigned to each base.
• Find short indels with paired end reads.
• Accurately find large scale genomic deletions and translocations with paired end reads.
• Discover potential CNVs by checking read depth.
• Evaluate the accuracy of raw base qualities from sequencers and help to check the systematic errors.

However, Maq can NOT:

• Do de novo assembly. (Maq can only call the consensus by mapping reads to a known reference.)
• Map shorts reads against themselves. (Maq can only find complete overlap between reads.)
• Align capillary reads or 454 reads to the reference. (Maq cannot align reads longer than 63bp.)

This package is likely to be useful for users working with genetics or genomic studies in biology who need to assembly DNA sequences from fixed-length sequencers.

massXpert is a program to simulate and analyse mass spectrometric data obtained on linear (bio-)polymers. It is the successor of GNU polyxmass.

Four modules allow:

• making brand new polymer chemistry definitions;
• using the definitions to perform easy calculations in a desktop calculator-like manner;
• performing sophisticated polymer sequence editing and simulations;
• perform m/z list comparisons;

Chemical simulations encompass cleavage (either chemical or enzymatic), gas-phase fragmentations, chemical modification of any monomer in the polymer sequence, cross-linking of monomers in the sequence, arbitrary mass searches, calculation of the isotopic pattern...

This program computes, for a nucleic acid duplex, the enthalpy, the entropy and the melting temperature of the helix-coil transitions. Three types of hybridisation are possible: DNA/DNA, DNA/RNA, and RNA/RNA. The program first computes the hybridisation enthalpy and entropy from the elementary parameters of each Crick's pair by the nearest-neighbor method. Then the melting temperature is computed. The set of thermodynamic parameters can be easily changed, for instance following an experimental breakthrough.

MIPE provides a standard format to exchange and/or storage of all information associated with PCR experiments using a flat text file. This will:

• allow for exchange of PCR data between researchers/laboratories
• enable traceability of the data
• prevent problems when submitting data to dbSTS or dbSNP
• enable the writing of standard scripts to extract data (e.g. a list of PCR primers, SNP positions or haplotypes for different animals)

Although this tool can be used for data storage, it's primary focus should be data exchange. For larger repositories, relational databases are more appropriate for storage of these data. The MIPE format could then be used as a standard format to import into and/or export from these databases.

MIPE was published in: Aerts J & Veenendaal T. MIPE - a XML-format to facilitate the storage and exchange of PCR-related data. Online Journal of Bioinformatics 6(2): 114-120 (2005).

MUMmer is a system for rapidly aligning entire genomes, whether in complete or draft form. For example, MUMmer 3.0 can find all 20-basepair or longer exact matches between a pair of 5-megabase genomes in 13.7 seconds, using 78 MB of memory, on a 2.4 GHz Linux desktop computer. MUMmer can also align incomplete genomes; it handles the 100s or 1000s of contigs from a shotgun sequencing project with ease, and will align them to another set of contigs or a genome using the NUCmer program included with the system. If the species are too divergent for DNA sequence alignment to detect similarity, then the PROmer program can generate alignments based upon the six-frame translations of both input sequences.

MUSCLE is a multiple alignment program for protein sequences. MUSCLE stands for multiple sequence comparison by log-expectation. In the authors tests, MUSCLE achieved the highest scores of all tested programs on several alignment accuracy benchmarks, and is also one of the fastest programs out there.

Mustang is an algorithm to align multiple protein structures. Given a set of PDB files, the program uses the spatial information in the Calpha atoms of the set to produce a sequence alignment. Based on a progressive pairwise heuristic the algorithm then proceeds through a number of refinement passes. Mustang reports the multiple sequence alignment and the corresponding superposition of structures.

When using this program please cite A.S. Konagurthu, J.C. Whisstock, P.J. Stuckey, A.M. Lesk, "MUSTANG: A multiple structural alignment algorithm." Proteins: Structure, Function, and Bioinformatics. 64(3):559-574.

Electronic PCR (e-PCR) is computational procedure that is used to identify sequence tagged sites(STSs), within DNA sequences. e-PCR looks for potential STSs in DNA sequences by searching for subsequences that closely match the PCR primers and have the correct order, orientation, and spacing that could represent the PCR primers used to generate known STSs.

The new version of e-PCR implements a fuzzy matching strategy. To reduce likelihood that a true STS will be missed due to mismatches, multiple discontigous words may be used instead of a single exact word. Each of this word has groups of significant positions separated by 'wildcard' positions that are not required to match. In addition, it is also possible to allow gaps in the primer alignments.

The main motivation for implementing reverse searching (called Reverse e-PCR) was to make it feasible to search the human genome sequence and other large genomes. The new version of e-PCR provides a search mode using a query sequence against a sequence database.

This package includes various utilities distributed with the NCBI C SDK. None of the programs in this package require X; you can find the X-based utilities in the ncbi-tools-x11 package. BLAST and related tools are in a separate package (blast2).

This package includes some X-based utilities distributed with the NCBI C SDK: Cn3D, Network Entrez, Sequin, ddv, and udv. These programs are not part of ncbi-tools-bin because they depend on several additional library packages.

NJplot is able to draw any dendrogram expressed in the Newick standard phylogenetic tree format (e.g., the format used by the Phylip package). NJplot is especially convenient for rooting the unrooted trees obtained from parsimony, distance or maximum likelihood tree-building methods.

PerlPrimer is a free, open-source GUI application written in Perl that designs primers for standard Polymerase Chain Reaction (PCR), bisulphite PCR, real-time PCR (QPCR) and sequencing. It aims to automate and simplify the process of primer design.

If operated online, the tool nicely communicates with the Ensembl project for further insights into the gene structure, i.e., allowing for taking the location of exons and introns into account for the design of the primers. The sequences themselves can be retrieved, too.

PhyML is a software that estimates maximum likelihood phylogenies from alignments of nucleotide or amino acid sequences. It provides a wide range of options that were designed to facilitate standard phylogenetic analyses. The main strengths of PhyML lies in the large number of substitution models coupled to various options to search the space of phylogenetic tree topologies, going from very fast and efficient methods to slower but generally more accurate approaches. It also implements two methods to evaluate branch supports in a sound statistical framework (the non-parametric bootstrap and the approximate likelihood ratio test).

PhyML was designed to process moderate to large data sets. In theory, alignments with up to 4,000 sequences 2,000,000 character-long can be analyzed. In practice however, the amount of memory required to process a data set is proportional of the product of the number of sequences by their length. Hence, a large number of sequences can only be processed provided that they are short. Also, PhyML can handle long sequences provided that they are not numerous. With most standard personal computers, the “comfort zone” for PhyML generally lies around 3 to 500 sequences less than 2,000 character long.

Plasmidomics is written for easy drawing of plasmids and vector maps to use them in theses, presentations or other forms of publications. It natively supports PostScript as output format.

plink expects as input the data from SNP (single nucleotide polymorphism) chips of many individuals and their phenotypical description of a disease. It finds associations of single or pairs of DNA variations with a phenotype and can retrieve SNP annotation from an online source.

SNPs can evaluated individually or as pairs for their association with the disease phenotypes. The joint investigation of copy number variations is supported. A variety of statistical tests have been implemented.

Please note: The executable was renamed to p-link because of a name clash. Please read more about this in /usr/share/doc/README.Debian.

POA is Partial Order Alignment, a fast program for multiple sequence alignment (MSA) in bioinformatics. Its advantages are speed, scalability, sensitivity, and the superior ability to handle branching / indels in the alignment. Partial order alignment is an approach to MSA, which can be combined with existing methods such as progressive alignment. POA optimally aligns a pair of MSAs and which therefore can be applied directly to progressive alignment methods such as CLUSTAL. For large alignments, Progressive POA is 10-30 times faster than CLUSTALW. POA is published in Bioinformatics. 2004 Jul 10;20(10):1546-56.

Primer3 picks primers for Polymerase Chain Reactions (PCRs), considering as criteria oligonucleotide melting temperature, size, GC content and primer-dimer possibilities, PCR product size, positional constraints within the source sequence, and miscellaneous other constraints. All of these criteria are user-specifiable as constraints, and some are specifiable as terms in an objective function that characterizes an optimal primer pair.

It has been published in Rozen S and Skaletsky H, "Primer3 on the WWW for general users and for biologist programmers.", Methods Mol Biol. 2000;132:365-86.

The Whitehead Institute for Biomedical Research provides a web-based front end to Primer3.

Tool for generating multiple alignments of protein sequences. Using a combination of probabilistic modeling and consistency-based alignment techniques, PROBCONS has achieved the highest accuracies of all alignment methods to date. On the BAliBASE benchmark alignment database, alignments produced by PROBCONS show statistically significant improvement over current programs, containing an average of 7% more correctly aligned columns than those of T-Coffee, 11% more correctly aligned columns than those of CLUSTAL W, and 14% more correctly aligned columns than those of DIALIGN. Probcons is published in Do, C.B., Mahabhashyam, M.S.P., Brudno, M., and Batzoglou, S. 2005. Genome Research 15: 330-340.

ProDA is a system for automated detection and alignment of homologous regions in collections of proteins with arbitrary domain architectures. Given an input set of unaligned sequences, ProDA identifies all homologous regions appearing in one or more sequences, and returns a collection of local multiple alignments for these regions.

ProDA is published in: Phuong T.M., Do C.B., Edgar R.C., and Batzoglou S. Multiple alignment of protein sequences with repeats and rearrangements. Nucleic Acids Research 2006 34(20), 5932-5942.

PyMOL is a molecular graphics system targetted at medium to large biomolecules like proteins. It can generate high-quality publication-ready molecular graphics images and animations.

Features include:

• Visualization of molecules, molecular trajectories and surfaces of crystallography data or orbitals
• Molecular builder and sculptor
• Internal raytracer and movie generator
• Fully extensible and scriptable via a Python interface

File formats PyMOL can read include PDB, XYZ, CIF, MDL Molfile, ChemDraw, CCP4 maps, XPLOR maps and Gaussian cube maps.

R/qtl is an extensible, interactive environment for mapping quantitative trait loci (QTLs) in experimental crosses. It is implemented as an add-on-package for the freely available and widely used statistical language/software R (see http://www.r-project.org).

The development of this software as an add-on to R allows to take advantage of the basic mathematical and statistical functions, and powerful graphics capabilities, that are provided with R. Further, the user will benefit by the seamless integration of the QTL mapping software into a general statistical analysis program. The goal is to make complex QTL mapping methods widely accessible and allow users to focus on modeling rather than computing.

A key component of computational methods for QTL mapping is the hidden Markov model (HMM) technology for dealing with missing genotype data. We have implemented the main HMM algorithms, with allowance for the presence of genotyping errors, for backcrosses, intercrosses, and phase-known four-way crosses.

The current version of R/qtl includes facilities for estimating genetic maps, identifying genotyping errors, and performing single-QTL genome scans and two-QTL, two-dimensional genome scans, by interval mapping (with the EM algorithm), Haley-Knott regression, and multiple imputation. All of this may be done in the presence of covariates (such as sex, age or treatment). One may also fit higher-order QTL models by multiple imputation.

The bio3d package contains utilities to process, organize and explore protein structure, sequence and dynamics data. Features include the ability to read and write structure, sequence and dynamic trajectory data, perform atom summaries, atom selection, re-orientation, superposition, rigid core identification, clustering, torsion analysis, distance matrix analysis, structure and sequence conservation analysis, and principal component analysis (PCA). In addition, various utility functions are provided to enable the statistical and graphical power of the R environment to work with biological sequence and structural data.

Most phenotypes of medical importance can be measured quantitatively, and in many cases the genetic contribution is substantial, accounting for 40% or more of the phenotypic variance. Considerable efforts have been made to isolate the genes responsible for quantitative genetic variation in human populations, but with little success, mostly because genetic loci contributing to quantitative traits (quantitative trait loci, QTL) have only a small effect on the phenotype. Association studies have been proposed as the most appropriate method for finding the genes that influence complex traits. However, family-based studies may not provide the resolution needed for positional cloning, unless they are very large, while environmental or genetic differences between cases and controls may confound population-based association studies.

These difficulties have led to the study of animal models of human traits. Studies using experimental crosses between inbred animal strains have been successful in mapping QTLs with effects on a number of different phenotypes, including behaviour, but attempts to fine-map QTLs in animals have often foundered on the discovery that a single QTL of large effect was in fact due to multiple loci of small effect positioned within the same chromosomal region. A further potential difficulty with detecting QTLs between inbred crosses is the significant reduction in genetic heterogeneity compared to the total genetic variation present in animal populations: a QTL segregating in the wild need not be present in the experimental cross.

The idea behind this package is that when multiple strains of animals that differ in their susceptibility to multiple diseases are bread over multiple generations, then one can analyse the contribution that a particular genetic locus has to each of those diseases. While in the past this approach has been performed for one disease at a time, this tool extends the statistics for allowing multiple crosses and thus save animal lifes. A larger stock of animals with more generations to keep them will further help producing larger numbers of observable cross-over events and thus help increasing the resolution of the mapping.

happy is an R interface into the HAPPY C package for fine-mapping Quantitative Trait Loci (QTL) in Heterogenous Stocks (HS). An HS is an advanced intercross between (usually eight) founder inbred strains of mice. HS are suitable for fine-mapping QTL. It uses a multipoint analysis which offers significant improvements in statistical power to detect QTLs over that achieved by single-marker association.

The happy package is an extension of the original C program happy; it uses the C code to compute the probability of descent from each of the founders, at each locus position, but the happy packager allows a much richer range of models to be fit to the data.

Further details can be found in

 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.230304397.

RasMol is a molecular graphics program intended for the visualisation of proteins, nucleic acids and small molecules. The program is aimed at display, teaching and generation of publication quality images.

The program reads in a molecule coordinate file and interactively displays the molecule on the screen in a variety of colour schemes and molecule representations. Currently available representations include depth-cued wireframes, 'Dreiding' sticks, spacefilling (CPK) spheres, ball and stick, solid and strand biomolecular ribbons, atom labels and dot surfaces.

Supported input file formats include Protein Data Bank (PDB), Tripos Associates' Alchemy and Sybyl Mol2 formats, Molecular Design Limited's (MDL) Mol file format, Minnesota Supercomputer Center's (MSC) XYZ (XMol) format, CHARMm format, CIF format and mmCIF format files.

This package installs two versions of RasMol, rasmol-gtk has a modern GTK-based user interface and rasmol-classic is the version with the old Xlib GUI.

Reads and writes nucleic/protein sequences in various formats. Data files may have multiple sequences. Readseq is particularly useful as it automatically detects many sequence formats, and converts between them.

RNAhybrid is a tool for finding the minimum free energy hybridisation of a long and a short RNA. The hybridisation is performed in a kind of domain mode, ie. The short sequence is hybridised to the best fitting part of the long one. The tool is primarily meant as a means for microRNA target prediction.

Public research assisted by RNAhybrid should cite: Marc Rehmsmeier, Peter Steffen, Matthias Höchsmann, Robert Giegerich Fast and effective prediction of microRNA/target duplexes RNA, 10:1507-1517, 2004.

Samtools is a set of utilities that manipulate nucleotide sequence alignments in the binary BAM format. It imports from and exports to the ascii SAM (Sequence Alignment/Map) format, does sorting, merging and indexing, and allows to retrieve reads in any regions swiftly. It is designed to work on a stream, and is able to open a BAM (not SAM) file on a remote FTP or HTTP server.

SeaView reads and writes various file formats (NEXUS, MSF, CLUSTAL, FASTA, PHYLIP, MASE, Newick) of DNA and protein sequences and of phylogenetic trees. Alignments can be manually edited. It drives the programs Muscle or Clustal W for multiple sequence alignment, and also allows to use any external alignment algorithm able to read and write FASTA-formatted files. It computes phylogenetic trees by parsimony using PHYLIP's dnapars/protpars algorithm, by distance with NJ or BioNJ algorithms on a variety of evolutionary distances, or by maximum likelihood using the program PhyML 3.0. SeaView draws phylogenetic trees on screen or PostScript files, and allows to download sequences from EMBL/GenBank/UniProt using the Internet.

The SIBsim4 project is based on sim4, which is a program designed to align an expressed DNA sequence with a genomic sequence, allowing for introns. SIBsim4 is a fairly extensive rewrite of the original code with the following goals:

• speed improvement;
• allow large, chromosome scale, DNA sequences to be used;
• provide more detailed output about splice types;
• provide more detailed output about polyA sites;
• misc code cleanups and fixes.

Sigma (“Simple greedy multiple alignment”) is an alignment program with a new algorithm and scoring scheme designed specifically for non-coding DNA sequence. It uses a strategy of seeking the best possible gapless local alignments, at each step making the best possible alignment consistent with existing alignments, and scores the significance of the alignment based on the lengths of the aligned fragments and a background model which may be supplied or estimated from an auxiliary file of intergenic DNA.

sim4 is a similarity-based tool for aligning an expressed DNA sequence (EST, cDNA, mRNA) with a genomic sequence for the gene. It also detects end matches when the two input sequences overlap at one end (i.e., the start of one sequence overlaps the end of the other).

sim4 employs a blast-based technique to first determine the basic matching blocks representing the "exon cores". In this first stage, it detects all possible exact matches of W-mers (i.e., DNA words of size W) between the two sequences and extends them to maximal scoring gap-free segments. In the second stage, the exon cores are extended into the adjacent as-yet-unmatched fragments using greedy alignment algorithms, and heuristics are used to favor configurations that conform to the splice-site recognition signals (GT-AG, CT-AC). If necessary, the process is repeated with less stringent parameters on the unmatched fragments.

The Short Sequence Assembly by K-mer search and 3′ read Extension (SSAKE) is a genomics application for aggressively assembling millions of short nucleotide sequences by progressively searching for perfect 3′-most k-mers using a DNA prefix tree. SSAKE is designed to help leverage the information from short sequences reads by stringently clustering them into contigs that can be used to characterize novel sequencing targets.

The io_lib from the Staden package is a library of file reading and writing code to provide a general purpose trace file (and Experiment File) reading interface. It has been compiled and tested on a variety of unix systems, MacOS X and MS Windows.

This package contains the programs that are distributed with the Staden io_lib for manipulating and converting sequencing data files, and in particular files to maniuplate short reads generated by second and third generation sequencers and stored in SRF format.

T-Coffee is a multiple sequence alignment package. Given a set of sequences (Proteins or DNA), T-Coffee generates a multiple sequence alignment. Version 2.00 and higher can mix sequences and structures.

T-Coffee allows the combination of a collection of multiple/pairwise, global or local alignments into a single model. It also allows to estimate the level of consistency of each position within the new alignment with the rest of the alignments. See the pre-print for more information

T-Coffee has a special called M-Coffee that makes it possible to combine the output of many multiple sequence alignment packages. In its published version, it uses MUSCLE, PROBCONS, POA, DiAlign-TS, MAFFT, Clustal W, PCMA and T-Coffee. A special version has been made for Debian, DM-Coffee, that uses only free software by replacing Clustal W by Kalign. Using the 8 Methods of M-Coffee can sometimes be a bit heavy. You can use a subset of your favorite methods if you prefer.

Theseus is a program that simultaneously superimposes multiple macromolecular structures. Theseus finds the optimal solution to the superposition problem using the method of maximum likelihood. By down-weighting variable regions of the superposition and by correcting for correlations among atoms, the ML superposition method produces very accurate structural alignments.

When macromolecules with different residue sequences are superimposed, other programs and algorithms discard residues that are aligned with gaps. Theseus, however, uses a novel superimposition algorithm that includes all of the data.

Developed by the TIGR institute this software detects coding sequences in bacteria and archea.

Glimmer is a system for finding genes in microbial DNA, especially the genomes of bacteria and archaea. Glimmer (Gene Locator and Interpolated Markov Modeler) uses interpolated Markov models (IMMs) to identify the coding regions and distinguish them from noncoding DNA.

TREE-PUZZLE (the new name for PUZZLE) is an interactive console program that implements a fast tree search algorithm, quartet puzzling, that allows analysis of large data sets and automatically assigns estimations of support to each internal branch. TREE-PUZZLE also computes pairwise maximum likelihood distances as well as branch lengths for user specified trees. Branch lengths can also be calculated under the clock-assumption. In addition, TREE-PUZZLE offers a novel method, likelihood mapping, to investigate the support of a hypothesized internal branch without computing an overall tree and to visualize the phylogenetic content of a sequence alignment.

This is the parallelized version of tree-puzzle.

TREE-PUZZLE (the new name for PUZZLE) is an interactive console program that implements a fast tree search algorithm, quartet puzzling, that allows analysis of large data sets and automatically assigns estimations of support to each internal branch. TREE-PUZZLE also computes pairwise maximum likelihood distances as well as branch lengths for user specified trees. Branch lengths can also be calculated under the clock-assumption. In addition, TREE-PUZZLE offers a novel method, likelihood mapping, to investigate the support of a hypothesized internal branch without computing an overall tree and to visualize the phylogenetic content of a sequence alignment.

TreeView X is an open source and multi-platform program to display phylogenetic trees. It can read and display NEXUS and Newick format tree files (such as those output by PAUP*, ClustalX, TREE-PUZZLE, and other programs). It allows to order the branches of the trees, and to export the trees in SVG format.

The program was written by Rod Page r.page@bio.gla.ac.uk using the wxWidgets C++ library. It was published in Computer Applications in the Biosciences. 1996 12: 357-358.

Velvet is a de novo genomic assembler specially designed for short read sequencing technologies, such as Solexa or 454, developed by Daniel Zerbino and Ewan Birney at the European Bioinformatics Institute (EMBL-EBI), near Cambridge, in the United Kingdom.

Velvet currently takes in short read sequences, removes errors then produces high quality unique contigs. It then uses paired read information, if available, to retrieve the repeated areas between contigs.

Wise2 is a package focused on comparisons of biopolymers, commonly DNA and protein sequences. There are many other packages which do this, probably the best known being BLAST package (from NCBI) and the Fasta package (from Bill Pearson). There are other packages, such as the HMMER package (Sean Eddy) or SAM package (UC Santa Cruz) focused on hidden Markov models (HMMs) of biopolymers.

Wise2's particular forte is the comparison of DNA sequence at the level of its protein translation. This comparison allows the simultaneous prediction of say gene structure with homology based alignment.

Wise2 also contains other algorithms, such as the venerable Smith-Waterman algorithm, or more modern ones such as Stephen Altschul's generalised gap penalties, or even experimental ones developed in house, such as dba. The development of these algorithms is due to the ease of developing such algorithms in the environment used by Wise2.

Wise2 has also been written with an eye for reuse and maintainability. Although it is a pure C package you can access its functionality directly in Perl. Parts of the package (or the entire package) can be used by other C or C++ programs without namespace clashes as all externally linked variables have the unique identifier Wise2 prepended.

EMBOSS explorer is a web-based graphical user interface to the EMBOSS suite of bioinformatics tools. It is written in Perl.

If you use the Apache HTTP server, you will at most have to restart it before using EMBOSS explorer. For other web servers, you will have to do the configuration by yourself.

This package provides a graphical user interface for the “melting” program, which computes for a nucleic acid duplex the enthalpy, the entropy and the melting temperature of the helix-coil transitions.

Code bioFOX aims at implementing various bioinformatics tools as an extension on the Iceape and Iceweasel browsers. Analysis of your favorite gene(s) usually require(s) retrieving it from a database like NCBI or Swiss-Prot and then performing one or more tasks including but not limited to:

• Translation of a nucleotide sequence;
• Blast search (eg. blastn, blastp etc.) of the desired nucleotide/protein sequence;
• Calculation of properties (like PI, charge, molecular weight, AT/GC content etc.) of a protein/nucleotide sequence;
• Conversion between formats (Genbank, Fasta, Swiss-Prot etc.);
• Prediction of sequence for sub-cellular localization (PREDOTAR, TargetP, pSORT etc).

SeqAn is a C++ template library of efficient algorithms and data structures for the analysis of sequences with the focus on biological data. This library applies a unique generic design that guarantees high performance, generality, extensibility, and integration with other libraries. SeqAn is easy to use and simplifies the development of new software tools with a minimal loss of performance. This package contains the applications dfi, pair_align, micro_razers, seqan_tcoffee, seqcons, razers and tree_recon.

The ARB software is a graphically oriented package comprising various tools for sequence database handling and data analysis. A central database of processed (aligned) sequences and any type of additional data linked to the respective sequence entries is structured according to phylogeny or other user defined criteria.

The ARB project (latin, "arbor"=tree) is a joint initiative of the Lehrstuhl fuer Mikrobiologie http://www.mikro.biologie.tu-muenchen.de/ and the Lehrstuhl fuer Rechnertechnik und Rechnerorganisation http://wwwbode.informatik.tu-muenchen.de/ of the Technical University of Munich.

This package is part of the mgltools set of Python libraries which provide an infrastructure for the analysis of protein structures and their docking of chemical compounds.

AutoDock is a well established package for the automated screening of libraries of formal representation of chemical compounds that putatively bind to a particular protein at hand. This package provides a graphical user interface that is helping with the preparation of the protein for such analyses.

This program performs an alignment of multiple nucleotide or amino acid sequences. It recognizes the format of input sequences and whether the sequences are nucleic acid (DNA/RNA) or amino acid (proteins). The output format may be selected from in various formats for multiple alignments such as Phylip or FASTA. Clustal W is very well accepted.

The output of Clustal W can be edited manually but preferably with an alignment editor like SeaView or within its companion Clustal X. When building a model from your alignment, this can be applied for improved database searches. The Debian package hmmer creates such in form of an HMM.

ClustalW is a popular tool for multiple sequence alignment. The alignment is achieved via three steps: pairwise alignment, guide-tree generation and progressive alignment. ClustalW-MPI is an MPI implementation of ClustalW. Based on version 1.82 of the original ClustalW, both the pairwise and progressive alignments are parallelized with MPI, a popular message passing programming standard. The pairwise alignments can be easily parallelized since the many alignments are time independent on each other. However the progressive alignments are essentially not parallelizable because of the time dependencies between each alignment.

Here the recursive parallelism paradigm is applied to the linear space profile-profile alignment algorithm. This approach is more time efficient on computers with distributed memory architecture. Traditional approach that relies on precomputing the profile-profile score matrix has also been implemented. Results shown the latter is indeed more appropriate for shared memory multiprocessor computer.

ClustalX is suggested for its support for local realignments, seaview is a versatile editor of alignments.

The original ClustalW/ClustalX can be found at URL: http://www.clustal.org/download/pre-2/

This package offers a GUI interface for the Clustal multiple sequence alignment program. It provides an integrated environment for performing multiple sequence- and profile-alignments to analyse the results. The sequence alignment is displayed in a window on the screen. A versatile coloring scheme has been incorporated to highlight conserved features in the alignment. For professional presentations, one should use the texshade LaTeX package or boxshade.

The pull-down menus at the top of the window allow you to select all the options required for traditional multiple sequence and profile alignment. You can cut-and-paste sequences to change the order of the alignment; you can select a subset of sequences to be aligned; you can select a sub-range of the alignment to be realigned and inserted back into the original alignment.

An alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted.