An access interface for the MS-DOS diskette format of GenBank(R), a gene sequence database

An interface program has been developed for users of MS-DOScomputers and the GenBank(R) gene sequence files in their disketteformat. With the program a user is able to produce keyword,author and entry name listings of GenBank items or to selectGenBank sequences for viewing, printing or decoding. The decodeoption uncompresses sequence data and yields a character filewhich has the format used on GenBank magnetic tapes. Programoptions are chosen by selecting items from command menus. Whilethe program is designed primarily for hard disk operation, italso allows users of diskette-based computers to work with GenBankfiles. Received on July 15, 1987; accepted on July 15, 1987     

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     

A program for template matching of protein sequences

The matching of a template to a protein sequence is simplifiedby treating it as a special case of sequence alignment. Restrictionof the distances between motifs in the template controls againstspurious matches within very long sequences. The program usingthis algorithm is fast enough to be used in scanning large databasesfor sequences matching a complex template. Received on August 17, 1987; accepted on January 11, 1988     

Two computer programs for rapid entry of DNA sequence data

Two computer programs for the IBM personal computer are describedfor rapid and accurate entry of DNA sequence data. The DNA sequencefiles produced can be used directly by the DNA sequence manipulationprograms by R. Staden (the DataBase system), the Universityof Wisconsin Genetics Computer Group, DNASTAR, or D. Mount.The first program, DIGISEQ, utilizes a sonic digitizer for semi-automationof sequence entry. To enter the DNA sequence each band of agel reading is touched by the stylus of the sonic digitizer.DIGISEQ corrects for both changes in lane width and lane curvature.The algorithm is extremely efficient and rarely requires re-entenngthe centers of the lanes. The second program, TYPESEQ, usesonly the keyboard for input. The keyboard is reconfigured toplace nucleotides and ambiguity codes under the fingers of onehand, corresponding to the order of the nucleotides on the geldefined by the user Both programs produce individual tones foreach nucleotide, and certain ambiguity codes. This verifiesinput of the correct nucleotide or ambiguity code, and thuseliminates the need to visually check the screen display duringsequence entry. Received on November 16, 1986; accepted on June 16, 1987     

A fixed-point alignment technique for detection of recurrent and common sequence motifs associated with biological features

A fixed-point alignment analysis technique is presented whichis designed to locate common sequence motifs in collectionsof proteins or nucleic acids. Initially a program aligns a collectionof sequences by a common sequence pattern or known biologicalfeature. The common pattern or feature (fixed-point) may bea user-specified sequence string or a known sequence positionlike mRNA start site, which may be taken directly from the annotatedfeature table of GenBank. Once all alignment markers are located,the sequences are scanned for occurrences of given oligomerswithin a specified span both upstream and downstream of thefixed-point. The occurrences may then be plotted as a functionof the position relative to the fixed-point, displayed as anactual sequence alignment or selectively summarized via variousprogram options. Applications of the technique are discussed. Received on August 17, 1987; accepted on November 17, 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     

The antigenic index: a novel algorithm for predicting antigenic determinants

In this paper, we introduce a computer algorithm which can beused to predict the topological features of a protein directlyfrom its primary amino acid sequence. The computer program generatesvalues for surface accessibility parameters and combines thesevalues with those obtained for regional backbone flexibilityand predicted secondary structure. The output of this algorithm,the antigenic index, is used to create a linear surface contourprofile of the protein. Because most, if not all, antigenicsites are located within surface exposed regions of a protein,the program offers a reliable means of predicting potentialantigenic determinants. We have tested the ability of this programto generate accurate surface contour profiles and predict antigenicsites from the linear amino acid sequences of well-characterizedproteins and found a strong correlation between the predictionsof the antigenic index and known structural and biological data. Received on August 17, 1987; accepted on December 31, 1987     

Modification of DNA ends and detection of restriction enzyme recognition sequences in their ligated junctions

A program has been developed for the modelling of modificationsin DNA ends, for the construction of ligated junctions, andfor the analysis in these junctions of new restriction enzymerecognition sequences. This program allows the analysis of restrictionenzyme specifities in ligated junctions of cohesive or bluntDNA ends. Cohesive ends are considered in their natural configurationor after modification by possible blunt-ending procedures. Theprogram also allows the modelling of partial filling-in for5'-single-stranded ends. This program has proven useful forthe design of sequences with new restriction sites or to predictor confirm the sequence of junctions created by the ligationof modified ends. Received on October 28, 1987; accepted on November 23, 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     

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     

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     

A flexible method to align large numbers of biological sequences

Summary A method for the alignment of two or more biological sequences is described. The method is a direct extension of the method of Taylor (1987) incorporating a consensus sequence approach and allows considerable freedom in the control of the clustering of the sequences. At one extreme this is equivalent to the earlier method (Taylor 1987), whereas at the other, the clustering approaches the binary method of Feng and Doolittle (1987). Such freedom allows the program to be adapted to particular problems, which has the important advantage of resulting in considerable savings in computer time, allowing very large problems to be tackled. Besides a detailed analysis of the alignment of the cytochrome c superfamily, the clustering and alignment of the PIR sequence data bank (3500 sequences approx.) is described.     

Multiple sequence alignment by a pairwise algorithm

An algorithm is described that processes the results of a conventionalpairwise sequence alignment program to automatically producean unambiguous multiple alignment of many sequences. Unlikeother, more complex, multiple alignment programs, the methoddescribed here is fast enough to be used on almost any multiplesequence alignment problem. Received on September 25, 1986; accepted on January 29, 1987     

PROTEUS: a suite of programs for prediction of structural features of proteins using an Apple lie

We have implemented several algorithms, developed by variousauthors for predicting structural features of proteins fromtheir primary structure, on an Apple lle and collected themin a suite, named PROTEUS. This suite incorporates: (i) methodsfor predicting secondary structure; (ii) the algorithm for computingthe hydropathy profile using one out of five available setsof parameters; (ii) the algorithms for calculating the hydrophobicmoment plot; and (iv) for performing the amphipathic analysisusing one out of four available sets of parameters. The suitehas a utility program for storing on a disk the sequence tobe analysed. As an example, we applied some of the methods includedin PROTEUS to predict the structure of a mitochondnal leaderpeptide. The results suggest the occurrence of structural featurespossibly related to the import of proteins into mitochondria. Received on April 30, 1987; accepted on July 21, 1987     

A computer program to display codon changes caused by mutagenesis

A FORTRAN program for displaying the correspondence betweencodon changes and different possible base changes is presented.Changes of both single bases and dimers are considered. Theuser can specify the mutagenesis spectrum. Additionally, theuser can choose whether or not to consider single or doubleevents in a codon and whether or not to consider the possibilitythat the change of two bases (a dimer) can overlap a codon boundary.Furthermore, a variety of ways may be chosen to display andsummarize the codon changes that can result from the specifiedmutagenesis. A user-supplied sequence or the genetic code tablecan be analyzed. Received on January 27, 1987; accepted on September 4, 1987     

FUGE: an analytical ultracentrifuge simulation for teaching purposes

An IBM-compatible microcomputer program for teaching purposesis described which simulates the operation of a sedimentationvelocity determination of a protein in an analytical ultracentrifugeusing schlieren optics. The program operates in speeded-up timeand simulates the major procedures which would need to be carriedout to operate such an instrument. The position of the sedimentingboundary can be observed at any time during the run, and upto six ‘photographs’ can be recorded for subsequentanalysis. Calculation of sedimentation coefficient, diffusioncoefficient and mol. wt can be made from a dot-matrix printout.Ten representative proteins are stored within the program, butprovision exists for user-supplied data. Received on June 25, 1987; accepted on September 9, 1987     

The significance of protein sequence similarities

A general method of assessing the significance of scored bestlocal alignments, particularly suited to protein sequence comparisons,is described. The method establishes the parameters describingthe distribution of the best results from any search program,provided that the set is sufficiently large and the majorityof the alignments arise from unrelated sequences. The expectedfrequency of occurrence of any score can then be calculated,together with the number of standard deviations above expectation.These provide sensible measures of significance without additionalsearch operations. However the biological significance of anyalignment or set of alignments does not solely depend on theimprobability of the alignment, but on all relevant factorsknown to the biologist. Received on August 9, 1987; accepted on November 17, 1987     

EMBOPRO--an automatically generated protein sequence database

For the identification of newly sequenced proteins it is necessaryto have a large stock of known proteins for comparison. In thispaper we present an automatically generated protein sequencedatabase. The translation program introduced allows a periodicaltranslation of every new release of the EMBL database. Possibleerrors of the translation are discussed as well as the reliabilityof the nucleotide sequence data, which turns out to be quitegood. A comparison of our translated database with some establishedones is given. Received on December 15, 1987; accepted on April 19, 1988     

A Macintosh computer program for designing DNA sequences that code for specific peptides and proteins

A computer program (PINCERS) is described for use in the design of synthetic genes and mixed-probe DNA sequences. A protein sequence is reverse translated with generation of synonymous codons at each position producing a degenerate sequence. In order to locate potential restriction enzyme sites, the degenerate sequence is searched with a library of restriction enzymes for sites that utilize any combination of synonymous codons. These sites are indicated in a map so that they may be incorporated into the synthetic gene sequence. The program allows the user to select the appropriate codon usage table for the organism of interest and then to set a threshold usage frequency below which codons are not generated. PINCERS may also be used to assist in planning the synthesis of mixed-probe DNA sequences for cross-hybridization experiments. It can identify regions of specified length with the protein sequence that have the least overall degeneracy, thereby minimizing the number of probes to be synthesized and, therefore, maximizing the concentration of a given probe sequence.