A program for drawing evolutionary trees

From the measures of evolutionary distance between pairs ofsequences in a set, it is possible to infer the genetic treeor trees which best fit these known data. DENDRON is a new program,written in FORTRAN 66, which computes an initial tree from thebottom-up, then searches among increasingly divergent treesfor a better fit. As a check on the consistency of the measures,the program tests all triplets for the triangle inequality.DENDRON also calculates a single ‘top-down’ tree,progressing from the trunk to the twigs, for comparison withthe ‘bottom-up’ trees. Received on August 17, 1987; accepted on June 1, 1988     

Programs for evaluating and characterising bacterial taxonomic data

Three programs are described for evaluating and characterisingdata collected during numerical taxonomic studies of bacteria.The program VARIANCE compares replicate cultures and evaluatesthe reproducibility of each character. Also it identifies thosecharacters that should be excluded from subsequent taxonomicanalysis because of their poor reproducibility. GPROPS summarisesthe properties of clusters of strains that have been definedfrom a cluster analysis, it can produce a probabilistic identificationmatrix and compares each strain within a cluster with the HypotheticalMean Organism (HMO) of that cluster. OVCLUST is an implementationof the program described by Sneath (1979) which calculates overlapstatistics between major clusters. These programs are designedto complement the CLUSTAN package (Wishart, 1982) which is oftenused for cluster analysis of bacterial taxonomic data. The programswere written in FORTRAN 77 and implemented on an IBM PC usingMS–DOS. Received on November 13, 1986; accepted on January 8, 1987     

An integrated family of amino acid sequence analysis programs

During the last years abundant sequence data has become availabledue to the rapid progress in protein and DNA sequencing techniques.The exact three-dimensional structures, however, are availableonly for a fraction of proteins with known sequences. For manypurposes the primary amino acid sequence of a protein can bedirectly used to predict important structural parameters. However,mathematical presentation of the calculated values often makesinterpretation difficult, especially if many proteins must beanalysed and compared. Here we introduce a broad-based, user-definedanalysis of amino acid sequence information. The program packageis based on published algorithms and is designed to access standardprotein data bases, calculate hydropathy, surface probabilityand flexibility values and perform secondary structure predictions.The data output is in an ‘easy-to-read’ graphicformat and several parameters can be superimposed within a singleplot in order to simplify data interpretations. Additionally,this package includes a novel algorithm for the prediction ofpotential antigenic sites. Thus the software package presentedhere offers a powerful means of analysing an amino acid sequencefor the purpose of structure/function studies as well as antigenicsite analyses. These algorithms were written to function incontext with the UWGCG (University of Wisconsin Genetics ComputerGroup) program collection, and are now distributed within thatpackage. Received on March 20, 1987; accepted on September 4, 1987     

A program for predicting significant RNA secondary structures

We describe a program for the analysis of RNA secondary structure.There are two new features in this program. (i) To get vectorspeeds on a vector pipeline machine (such as Cray X-MP/24) wehave vectorized the secondary structure dynamic algorithm. (ii)The statistical significance of a locally ‘optimal’secondary structure is assessed by a Monte Carlo method. Theresults can be depicted graphically including profiles of thestability of local secondary structures and the distributionof the potentially significant secondary structures in the RNAmolecules. Interesting regions where both the potentially significantsecondary structures and ‘open’ structures (single-strandedcoils) occur can be identified by the plots mentioned above.Furthermore, the speed of the vectorized code allows repeatedMonte Carlo simulations with different overlapping window sizes.Thus, the optimal size of the significant secondary structureoccurring in the interesting region can be assessed by repeatingthe Monte Carlo simulation. The power of the program is demonstratedin the analysis of local secondary structures of human T-celllymphotrophic virus type III (HIV). Received on August 17, 1987; accepted on January 5, 1988     

A program for the graphic representation and manipulation of DNA sequences

We have developed a program for the graphic representation andmanipulation of DNA sequences. The program (named CARTE fromthe French for ‘map’) is intended as a tool in theplanning and analysis of recombinant DNA experiments. DNA sequencesare represented as standard restriction maps, using any desiredcombination of restriction enzymes. Features of interest, suchas promoters or coding sequences, can be highlighted. The sequencecan be manipulated to mimic cloning, using deletions, insertionsor replacements at specified sites. This process is facilitatedby the simultaneous display of a graphic map of the entire sequence,a detailed picture of the work in progress, and a menu of functions. Received on November 17, 1986; accepted on March 12, 1987     

RNA secondary structures: comparison and determination of frequently recurring substructures by consensus

A method for assessing the preserved stem - loops of RNA secondarystructures is presented. Frequently recurring helical stemsin a set of secondary structures resulting from the simulatedfolding process of a given RNA are assessed and consensus structuralmotifs can then be selected to construct a secondary structureof the RNA. Alternatively, it can be applied to a series of‘optimal’ and ‘suboptimal’ secondarystructures computed using the dynamic program developed by Williamsand Tinoco. To demonstrate the power and the usefulness of theprogram we give examples of this procedure. Received on October 28, 1987; accepted on April 2, 1989     

Two different approaches to computer-aided teaching of microbial genetics

Two computer packages have been developed to teach bacterialgenetics on an introductory genetics course for undergraduatestudents in biology. The first package, ‘CONJUGACION’,is designed to teach bacterial conjugation and its genetic outcomes.It includes four main parts. Firstly, a tutorial part presentsa theoretical framework using screens of text and animated graphics.Secondly, an interactive concept application section requiresstudents to carry out experiments for the determination of thecorrect sex and genotype of 10 bacterial strains. The thirdpart uses the previously obtained data for simulating interruptedmating experiments and mapping the bacterial genome. Finally,an evaluation section allows the students to test their understandingthrough a series of multiple choice questions. The second package,‘LURIDEL’, is intended for teaching the preadaptativecharacter of mutation in bacterial populations on the basisof the fluctuation test of Luria and Delbruck. It simulates,graphically, the appearance of mutations in microbial culturesand gives results of simulated fluctuation experiments. Programswere written under the PCOS operating system in MBASIC extendedto graphics for running on Olivetti M20 microcomputers. Received on December 3, 1986; accepted on February 17, 1987     

PARA-SITE: a computer algorithm for rapidly analyzing the physical-chemical properties of amino acid sequences at sites of co- and post-translational protein processing

A new algorithm is presented which can be used to examine thephysical-chemical properties of amino acids at sites of co-orpost-translational processing. This algorithm has been incorporatedinto a computer program known as PARA-SITE. Thirty differentparameters can be studied for amino acids which occupy comparablepositions in naturally occurring proteins. PARA-SITE shouldaid in the design and interpretation of protein engineeringexperiments which seek to dissect structure/ activity relationships. Received on August 17, 1987; accepted on November 23, 1987     

Graphics of RNA secondary structure; towards an object-oriented algorithm

We present a new algorithm for the display of RNA secondarystructure. The principle of the algorithm is entirely differentfrom those currently in use in that our algorithm is ‘objectoriented’ while currrent algorithms are ‘procedural’.The circular RNA molecule of chrysanthemum stunt viroid wasused as input data for demonstrating the operation of the program.The major interest of this method will be found in its potentialuse in simulation graphics of RNA folding processes. Received on October 9, 1986; accepted on February 17, 1987     

A secondary and tertiary structure editor for nucleic acids

A major difficulty in the evaluation of secondary and tertiarystructures of nucleic acids is the lack of convenient methodsfor their construction and representation. As a first step ina study of the symbolic representation of biopolymers, we reportthe development of a structure editor written in Pascal, permittingmodel construction on the screen of a personal computer. Theprogram calculates energies for helical regions, allows user-definedhelices and displays the secondary structure of a nucleic acidbased on a user-selected set of helices. Screen and printeroutputs can be in the form of a backbone or the letters of theprimary sequence. The molecule can then be displayed in a formatwhich simulates its three-dimensional structure. Using appropriateglasses, the molecule can be viewed on the screen in three dimensions.Other options include the manipulation of helices and single-strandedregions which results in changes in the spatial relationshipbetween different regions of the molecule. The editor requiresan IBM or compatible PC, 640 kbyte memory and a medium or highresolution graphics card. Received on September 19, 1987; accepted on November 15, 1987     

Computer video acquisition and analysis system for biological data

The BIAS (Biological Image Analysis System) was developed to:(i) permit accurate entry and image processing of biologicaldata; (ii) minimize the need for specialized hardware; and (iii)aid in the human genome mapping and other projects. The firstmouse/cursor key-driven module was designed to be user interactiveand readily accessible to many laboratories. It contains theDRSNDS programs which automate the entering of data in a systematicformat. The types of data that can be entered utilizing thismodule are DNA — RNA gels from either a positive or negativePolaroid^TM image, autoradiograms or biotinylated images fromSouthern, Northern and dot or slot blot hybridization analyses.The image is acquired using a video camera and then digitizedfor subsequent analysis. During the analysis graphical representationsof the intermediate results are provided to assure user confidence.At any point within the program the user may obtain on-linehelp with the current task. The output displays the mol. wtof each individual component in the appropriate context. Thepresent version of the program produces results comparable witha human interpreter for some data. Band shifting and opticaldensity calculations are in a prototype form to permit evaluationof various techniques. Future work is directed at expandingthe system's capabilities to interpret data from other biologicalanalyses including DNA sequencing gels. Received on December 1, 1987; accepted on December 12, 1987     

Redasoft Plasmid 1.1: software for easy, efficient cloning and map drawing

A computer program is described which creates circular and linear genetic maps with or without sequences, performs restriction analysis, and simulates basic molecular cloning operations. Redasoft Plasmid 1.1 is a user-friendly program for Windows 95/98/NT/2000, designed to generate high quality genetic maps for presentation and publication and to aid the molecular biologist in selecting restriction endonucleases for common molecular cloning experiments. The program incorporates an integrated web browser and can automatically generate complete, labeled maps from sequences on the Internet.     

BCETM: a tool for software integration

The integration of software into special-purpose systems (e.g.for gene sequence analysis) can be a difficult task. We describea general-purpose software integration tool, the BCETM program,that facilitates assembly of VAX-based software into applicationsystems and provides an easy-to-use, intuitive user interface.We describe the use of BCE to integrate a heterogeneous collectionof sequence analysis tools. Many BCE design features are generallyapplicable and can be implemented in other language or hardwareenvironments. Received on May 13, 1987; accepted on October 2, 1987     

AUGUR: a program to predict, display and analyze the tertiary structure of B-DNA

A UGUR is a program to predict, display and analyze the three-dimensionalstructure of B-DNA. The user can choose one of six models topredict the helical parameters of a given sequence. These parametersare then used to generate the coordinates of the DNA model inthree-dimensional space (trajectory). The trajectory can bedisplayed and rotated on a graphics terminal The trajectoryand helical parameters can also be searched for bends and structuralhomologues. Received on August 17, 1987; accepted on December 31, 1987     

HOMED: a homologous sequence editor

The alignment of homologous sequences with each other and theirdisplay has proved a–difficult task, despite a frequentrequirement for this process. HOMED enables related sequencesto be edited and listed in parallel with each other. The editorfunction uses a full screen editor which emulates the text editorsKED and EDT (on PDP–11 and VAX–11 respectively)and which can be adapted to emulate other text editors. Thisemulation has been adopted to simplify user learning of editingfunctions. HOMED provides functions for listing the sequencesin a variety of formats and for generating a consensus sequenceas well as providing a series of tools for maintenance of thesequence database. HOMED has been implemented in Pascal in amodular fashion to enhance portability. Received on November 27, 1986; accepted on January 8, 1987     

Restriction map construction using a 'complete sentences compatibility' algorithm

We have developed a new algorithm ‘Complete sentencescompatibility’ (CSC) which uses single and double digestionfragments to rapidly determine restriction maps of circularDNA. From possible combinations of fragments of each simpledigestion, which we call ‘sentences of decomposition’,we construct a restriction map which combines the sentenceswhile taking into account compatibility rules. The algorithmcan also deal with experimental errors of fragment weight andcan suggest solutions that account for non-readable bands (fragmentsof zero length or multiple bands) on the gel. Because experimentsusing pairs of restrictive enzymes often result in multiplesolutions, a complementary algorithm tries to reduce the numberof proposed solutions by establishing consensus maps. The restrictionmap construction algorithm was tested on real cases, some containingmore than fifteen fragments. Execution times range from 1 –10 s on an IBM PC compatible microcomputer. Received on July 21, 1987; accepted on December 31, 1987     

Matching relational patterns in nucleic acid sequences

We describe a program that efficiently searches sequence databanks for complex patterns where sites are linked by commonrelations such as identity, complementarity or span. Its algorithmis closer to those of automatic demonstration than to the finitestate machines used in fast pattern matching. The repertoryof relations can be enriched at will without rewriting the coreof the program. The program is written in Pascal-ISO and runson a microcomputer. Received on September 25, 1986; accepted on April 30, 1987     

The use of various properties of amino acids in color and monochrome dot-matrix analyses for protein homologies

Software has been developed to allow the use of a number ofparameters in the comparative representation of proteins incolor and monochrome dot matrices. They include the parametersof partial specific volume, residue bulkiness, the mean areaburied of side chains, seven additional hydropathy scales, mutability,polarity, secondary structure propensities, energy/residue,energy/atom, R_f values, the pKs at the N and C terminals, user-definedparameters and, if desired, randomly generated values. Manyof these parameters can be combined in n space using an algorithmbased on the Euclidian distance relationship in order to deriveconsensus values. The problem of scoring matched identitiesis addressed and the user may stipulate that they score 100on a 0–100 scale or be determined from the Dayhoff MDM₇₈values with the rest of the matrix scaled appropriately. ThePAMs matrix has been incorporated in such a way to allow theuser to stipulate various PAM's values or estimated percentagedifference between two peptide sequences, and converting tolog odds values. In addition, the similarity ring developedby Swanson and the matrix proposed by Bacon and Anderson havebeen adapted for use in the program. Color indices have beenutilized to give a ‘third dimension’ to the projections,allowing the user to judge the degree of similarity of differentregions which are represented. The software also provides forthe plotting of nucleotides in which case color is used to codeindividual nucleotides, purines versus pyrimidines, or similarcolors are used to differentiate between A and T bases on theone hand, and G and C on the other. Received on December 31, 1987; accepted on May 18, 1988     

Optimal alignments of biological sequences on a microcomputer

An algorithm and a program have been developed which enableoptimal alignments of biological sequences on an 8–bitmicrocomputer. The compiled program can process sequences upto 1000 residues on a Commodore 64. Since this program was writtenoriginally in the BASIC language, it may readily be adaptedto other microcomputers with small changes. Received on March 11, 1985; accepted on March 14, 1985     

Hand-held computer program for field-capture and analysis of herbage yield and composition data using a modified dry-weight-rank and yield estimate method

A BASIC program is described which is used to collect, checkand analyse rank estimates of plant yield in the field. Theprogram operates in a portable, battery-powered Sharp PCI500Ahand-held computer than can be used in a field environment.Data are collected using a modified dry-weight-rank method andcomparative yield estimates. Much of the software is designedto trap incorrect data entry. Raw data or summary data may beprinted, displayed, and stored on cassette tape or transferredto another computer through a communications interface. Theprogram can be easily modified to run on other models of theSharp PC series or other portable computers that use a similarBASIC interpreter. Received on July 2, 1987; accepted on August 6, 1987