The current status and portability of our sequence handling software.

I describe the current status of our sequence analysis software. The package contains a comprehensive suite of programs for managing large shotgun sequencing projects, a program containing 61 functions for analysing single sequences and a program for comparing pairs of sequences for similarity. The programs that have been described before have been improved by the addition of new functions and by being made very much easier to use. The major interactive programs have 125 pages of online help available from within them. Several new programs are described including screen editing of aligned gel readings for shotgun sequencing projects; a method to highlight errors in aligned gel readings, new methods for searching for putative signals in sequences. We use the programs on a VAX computer but the whole package has been rewritten to make it easy to transport it to other machines. I believe the programs will now run on any machine with a FORTRAN77 compiler and sufficient memory. We are currently putting the programs onto an IBM PC XT/AT and another micro running under UNIX.     

Apple Macintosh programs for nucleic and protein sequence analyses

This paper describes a package of programs for handling and analyzing nucleic acid and protein sequences using the Apple Macintosh microcomputer. There are three important features of these programs: first, because of the now classical Macintosh interface the programs can be easily used by persons with little or no computer experience. Second, it is possible to save all the data, written in an editable scrolling text window or drawn in a graphic window, as files that can be directly used either as word processing documents or as picture documents. Third, sequences can be easily exchanged with any other computer. The package is composed of thirteen programs, written in Pascal programming language.     

ANTHEPROT: a package for protein sequence analysis using a microcomputer

A simple microcomputer package is described to make the theoreticalanalysis of protein sequences. Several methods designed to comparetwo sequences, to model proteolytic reactions and to predictthe secondary structure, the hydro-phobic/hydrophilic regionsand the potential antigenic sites of proteins have been includedin an Apple II microcomputer software. The package comprises21 programs as well as the secondary structure database of Kabschand Sander (1983). Received on November 24, 1987; accepted on March 8, 1988     

FAST: Fourier transform based algorithms for significance testing of ungapped multiple alignments

SUMMARY: As was shown in Nagarajan et al. (2005), commonly used approximations for assessing the significance of multiple alignments can be be very inaccurate. To address this, we present here the FAST package, an open-source collection of programs and libraries for efficiently and reliably computing the significance of ungapped local alignments. We also describe other potential applications in Bioinformatics where these programs can be adapted for significance testing. AVAILABILITY: The FAST package includes C++ implementations of various algorithms that can be used as stand-alone programs or as a library of subroutines. The package and a web-server for some of the programs are available at www.cs.cornell.edu/~keich/FAST.     

Improved programs for DNA and protein sequence analysis on the IBM personal computer and other standard computer systems.

We have previously described programs for a variety of types of sequence analysis (1-4). These programs have now been integrated into a single package. They are written in the standard C programming language and run on virtually any computer system with a C compiler, such as the IBM/PC and other computers running under the MS/DOS and UNIX operating systems. The programs are widely distributed and may be obtained from the authors as described below.     

A convenient and adaptable microcomputer environment for DNA and protein sequence manipulation and analysis.

We describe the further development of a widely used package of DNA and protein sequence analysis programs for microcomputers (1,2,3). The package now provides a screen oriented user interface, and an enhanced working environment with powerful formatting, disk access, and memory management tools. The new GenBank floppy disk database is supported transparently to the user and a similar version of the NBRF protein database is provided. The programs can use sequence file annotation to automatically annotate printouts and translate or extract specified regions from sequences by name. The sequence comparison programs can now perform a 5000 X 5000 bp analysis in 12 minutes on an IBM PC. A program to locate potential protein coding regions in nucleic acids, a digitizer interface, and other additions are also described.     

VOSTORG: a package of microcomputer programs for sequence analysis and construction of phylogenetic trees

VOSTORG is a new, versatile package of programs for the inference and presentation of phylogenetic trees, as well as an efficient tool for nucleotide (nt) and amino acid (aa) sequence analysis (sequence input, verification, alignment, construction of consensus, etc.). On appropriately equipped systems, these data can be displayed on a video monitor or printed as required. They are implemented on IBM PC/XT/AT/PS-2 or compatible computers and hardware graphic support is recommended. The package is designed to be easily handled by occasional computer users and yet it is powerful enough for experienced professionals.     

Development and implementation of a general compiler to produce specific programs for minicomputer control of physiological experiments in real time

A method for automatic generation of specific FORTRAN programs to control physiological experiments with a computer was developed. The general real-time software package is built into a high level language (MAB = MAcro Basic). From this package, the scientist can automatically generate for him/herself specific programs for controlling his own experiments by a simple procedure. The generated programs contain only the relevant code, adjusted dimensions of arrays, names of parameters, and formatting for printing of tables and graphics for the particular experiment. Therefore, the resulting program is efficient both in terms of memory utilization and in execution time.     

Adopting a database as a solution to managing electron image data

A database was used for data management and interprogram communication in an image processing and three-dimensional reconstruction program suite for biological bundles. The programs were modified from the MRC crystallographic package. The database server works with local and remote programs and data sets, allows simultaneous requests from multiple clients, and maintains multiple databases and data tables within them. It has built-in security for the data access. Several graphical user interfaces are available to view and/or edit data tables. In addition, FORTRAN interface and function libraries are written to communicate with image processing software. The data management overhead is inexpensive, requiring only narrow bandwidth from the network. It easily handles several data tables with over 1000 entries.     

IMIRS: a high-resolution 3D reconstruction package integrated with a relational image database

Recent advances in electron cryomicroscopy instrumentation and single particle reconstruction have created opportunities for high-throughput and high-resolution three-dimensional (3D) structure determination of macromolecular complexes. However, it has become impractical and inefficient to rely on conventional text file data management and command-line programs to organize and process the increasing numbers of image data required in high-resolution studies. Here, we present a distributed relational database for managing complex datasets and its integration into our high-resolution software package IMIRS (Image Management and Icosahedral Reconstruction System). IMIRS consists of a complete set of modular programs for icosahedral reconstruction organized under a graphical user interface and provides options for user-friendly, step-by-step data processing as well as automatic reconstruction. We show that the integration of data management with processing in IMIRS automates the tedious tasks of data management, enables data coherence, and facilitates information sharing in a distributed computer and user environment without significantly increasing the time of program execution. We demonstrate the applicability of IMIRS in icosahedral reconstruction toward high resolution by using it to obtain an 8-A 3D structure of an intermediate-sized dsRNA virus.     

GenomeDiagram: a python package for the visualization of large-scale genomic data

SUMMARY: We present GenomeDiagram, a flexible, open-source Python module for the visualization of large-scale genomic, comparative genomic and other data with reference to a single chromosome or other biological sequence. GenomeDiagram may be used to generate publication-quality vector graphics, rastered images and in-line streamed graphics for webpages. The package integrates with datatypes from the BioPython project, and is available for Windows, Linux and Mac OS X systems. AVAILABILITY: GenomeDiagram is freely available as source code (under GNU Public License) at http://bioinf.scri.ac.uk/lp/programs.html, and requires Python 2.3 or higher, and recent versions of the ReportLab and BioPython packages. SUPPLEMENTARY INFORMATION: A user manual, example code and images are available at http://bioinf.scri.ac.uk/lp/programs.html.     

Computer programs for the analysis and the management of DNA sequences.

A program package is described for the management and the analysis of DNA sequence data. The programs - with the exception of a few Fortran routines - are written in the programming language APL. They are best used interactively although batch processing is possible. The package has been in constant use for about 3 years and contains programs for most of the routine problems presently found in a DNA sequencing laboratory.     

PGDSpider: an automated data conversion tool for connecting population genetics and genomics programs

The analysis of genetic data often requires a combination of several approaches using different and sometimes incompatible programs. In order to facilitate data exchange and file conversions between population genetics programs, we introduce PGDSpider, a Java program that can read 27 different file formats and export data into 29, partially overlapping, other file formats. The PGDSpider package includes both an intuitive graphical user interface and a command-line version allowing its integration in complex data analysis pipelines. AVAILABILITY: PGDSpider is freely available under the BSD 3-Clause license on http://cmpg.unibe.ch/software/PGDSpider/.     

MUST, a computer package of Management Utilities for Sequences and Trees.

The MUST package is a phylogenetically oriented set of programs for data management and display, allowing one to handle both raw data (sequences) and results (trees, number of steps, bootstrap proportions). It is complementary to the main available software for phylogenetic analysis (PHYLIP, PAUP, HENNING86, CLUSTAL) with which it is fully compatible. The first part of MUST consists of the acquisition of new sequences, their storage, modification, and checking of sequence integrity in files of aligned sequences. In order to improve alignment, an editor function for aligned sequences offers numerous options, such as selection of subsets of sequences, display of consensus sequences, and search for similarities over small sequence fragments. For phylogenetic reconstruction, the choice of species and portions of sequences to be analyzed is easy and very rapid, permitting fast testing of numerous combinations of sequences and taxa. The resulting files can be formatted for most programs of tree construction. An interactive tree-display program recovers the output of all these programs. Finally, various modules allow an in-depth analysis of results, such as comparison of distance matrices, variation of bootstrap proportions with respect to various parameters or comparison of the number of steps per position. All presently available complete sequences of 28S rRNA are furnished aligned in the package. MUST therefore allows the management of all the operations required for phylogenetic reconstructions.     

Detailed comparison of the protein-ligand docking efficiencies of GOLD, a commercial package and ArgusLab, a licensable freeware

Molecular docking and virtual screening based on molecular docking have become an integral part of many modern structure-based drug discovery efforts. Hence, it becomes a useful endeavor to evaluate existing docking programs, which can assist in the choice of the most suitable docking algorithm for any particular study. The objective of the current study was to evaluate the ability of ArgusLab 4.0, a relatively new molecular modeling package in which molecular docking is implemented, to reproduce crystallographic binding orientations and to compare its accuracy with that of a well established commercial package, GOLD. The study also aimed to evaluate the effect of the nature of the binding site and ligand properties on docking accuracy. The three dimensional structures of a carefully chosen set of 75 pharmaceutically relevant protein-ligand complexes were used for the comparative study. The study revealed that the commercial package outperforms the freely available docking engine in almost all the parameters tested. However, the study also revealed that although lagging behind in accuracy, results from ArgusLab are biologically meaningful. This taken together with the fact that ArgusLab has an easy to use graphical user interface, means that it can be employed as an effective teaching tool to demonstrate molecular docking to beginners in this area.     

A collection of programs for nucleic acid and protein analysis, written in FORTRAN 77 for IBM-PC compatible microcomputers.

We have developed a collection of programs for manipulation and analysis of nucleotide and protein sequences. The package was written in Fortran 77 on a Sirius1/Victor microcomputer which can be easily implemented on a large variety of other computers. Some of the programs have already been adapted for use on a Vax 11. Our aim was to develop programs consisting of small, comprehensible and well documented units that have very fast execution times and are comfortably interactive. The package is therefore suitable for individual modifications, even with little understanding of computer languages.     

Coordinated conditional simulation with SLINK and SUP of many markers linked or associated to a trait in large pedigrees

Simulation of genotypes in pedigrees is an important tool to evaluate the power of a linkage or an association study and to assess the empirical significance of results. SLINK is a widely-used package for pedigree simulations, but its implementation has not previously been described in a published paper. SLINK was initially derived from the LINKAGE programs. Over the 20 years since its release, SLINK has been modified to incorporate faster algorithms, notably from the linkage analysis package FASTLINK, also derived from LINKAGE. While SLINK can simulate genotypes on pedigrees of high complexity, one limitation of SLINK, as with most methods based on peeling algorithms to evaluate pedigree likelihoods, is the small number of linked markers that can be generated. The software package SUP includes an elegant wrapper for SLINK that circumvents the limitation on number of markers by using descent markers generated by SLINK to simulate a much larger number of markers on the same chromosome, linked and possibly associated with a trait locus. We have released new coordinated versions of SLINK (3.0; available from http://watson.hgen.pitt.edu) and SUP (v090804; available from http://mlemire.freeshell.org/software or http://watson.hgen.pitt.edu) that integrate the two software packages. Thereby, we have removed some of the previous limitations on the joint functionality of the programs, such as the number of founders in a pedigree. We review the history of SLINK and describe how SLINK and SUP are now coordinated to permit the simulation of large numbers of markers linked and possibly associated with a trait in large pedigrees.     

SDSE: A software package to simulate the evolution of a pair of DNA sequences

An algorithm to simulate DNA sequence evolution under a generalstochastic model, including as particular cases all the previouslyused schemes of nucleotide substitution, is described. The simulationis carried out on finite, variable length, DNA sequences througha strict stochastic process, according to the particular substitutionrates imposed by each scheme. Five FORTRAN programs, runningon an IBM PC and compatibles, carry out all the tasks neededfor the simulation. They are menu driven and interfaced to thesystem through a principal menu. All sequence data files usedand generated by the SDSE package conform to the standard GenBankdatabase format, thus allowing the use of any sequence retrievedfrom this databank, as well as the application of other packagesto analyse, manipulate or retrieve simulated sequences. Received on August 23, 1988; accepted on November 15, 1988