The staden sequence analysis package

I describe the current version of the sequence analysis package developed at the MRC Laboratory of Molecular Biology, which has come to be known as the “Staden Package.” The package covers most of the standard sequence analysis tasks such as restriction site searching, translation, pattern searching, comparison, gene finding, and secondary structure prediction, and provides powerful tools for DNA sequence determination. Currently the programs are only available for computers running the UNIX operating system. Detailed information about the package is available from our WWW site: http://www.mrc-lmb.cam.ac.uk/pubseq/.     

ISHAN: sequence homology analysis package

Sequence based homology studies play an important role in evolutionary tracing and classification of proteins. Various methods are available to analyze biological sequence information. However, with the advent of proteomics era, there is a growing demand for analysis of huge amount of biological sequence information, and it has become necessary to have programs that would provide speedy analysis. ISHAN has been developed as a homology analysis package, built on various sequence analysis tools viz FASTA, ALIGN, CLUSTALW, PHYLIP and CODONW (for DNA sequences). This JAVA application offers the user choice of analysis tools. For testing, ISHAN was applied to perform phylogenetic analysis for sets of Caspase 3 DNA sequences and NF-kappaB p105 amino acid sequences. By integrating several tools it has made analysis much faster and reduced manual intervention.     

ADSP-a new package for computational sequence analysis

A new protein sequence analysis package, ADSP, is described,of which the SOMAP Screen–Oriented Multiple AlignmentProcedure forms an integral part. ADSP (Algorithms and DataStructures for Protein sequence analysis) incorporates facilitiesto generate potent pattern-recognition discriminators and offersfour algorithms with which to scan any NBRF format sequencedatabase: the package has been designed, in particular, to interfacewith the OWL composite sequence database, one of the largest,distributed non-redundant sources of sequence data of its kind.The system incorporates a powerful method for compound featureanalysis, which provides the basis for characterizing and predictingthe occurrence of complete protein superfamilies and for pinpointingthe emergence of related subfamilies. Used iteratively, theapproach allows diagnostic performance to be rigorously refinedand its efficacy to be assessed both qualitatively and quantitatively,and results in the generation of refined structural or functionalfeatures suitable for entry into a database: this compilationof characteristic signatures is distinct from, but complementaryto, widely used compendia of pattern templates such as PROSUE.     

A menu-shell for the GCG programs

We provide a menu-driven integration of the genetic programsof the Genetics Computer Group (GCG). This allows inexperiencedusers a very simple access to all GCG programs regardless ofthe system environment. No modifications to the GCG packageare necessary. Received on October 25, 1990; accepted on March 14, 1991     

A convenient and adaptable package of DNA sequence analysis programs for microcomputers

We describe a package of DNA data handling and analysis programs designed for microcomputers. The package is convenient for immediate use by persons with little or no computer experience, and has been optimized by trial in our group for a year. By typing a single command, the user enters a system which asks questions or gives instructions in English. The system will enter, alter, and manage sequence files or a restriction enzyme library. It generates the reverse complement, translates, calculates codon usage, finds restriction sites, finds homologies with various degrees of mismatch, and graphs amino acid composition or base frequencies. A number of options for data handling and printing can be used to produce figures for publication. The package will be available in ANSI Standard FORTRAN for use with virtually any FORTRAN compiler.     

Genome-tools: a flexible package for genome sequence analysis

Genome-tools is a Perl module, a set of programs, and a user interface that facilitates access to genome sequence information. The package is flexible, extensible, and designed to be accessible and useful to both nonprogrammers and programmers. Any relatively well-annotated genome available with standard GenBank genome files may be used with genome-tools. A simple Web-based front end permits searching any available genome with an intuitive interface. Flexible design choices also make it simple to handle revised versions of genome annotation files as they change. In addition, programmers can develop cross-genomic tools and analyses with minimal additional overhead by combining genome-tools modules with newly written modules. Genome-tools runs on any computer platform for which Perl is available, including Unix, Microsoft Windows, and Mac OS. By simplifying the access to large amounts of genomic data, genome-tools may be especially useful for molecular biologists looking at newly sequenced genomes, for which few informatics tools are available. The genome-tools Web interface is accessible at http://genome-tools.sourceforge.net, and the source code is available at http://sourceforge.net/projects/genome-tools.     

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

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

A hybrid sequence approach to the paracelsus challenge

Inspired by the Paracelsus Challenge of Rose and Creamer (Proteins 19:1–3, 1994), we have designed a protein sequence that is 50% identical to an all-helical protein but is intended to fold into a largely β-sheet structure. Rather than attempt a de novo design, our strategy was to construct a hybrid sequence based on a helical “parent” protein (434 Cro) and a “target” protein with the desired fold (the B1 domain of protein G). The hybrid sequence (Crotein-G) is 50% identical to 434 Cro but is also 62% identical to the B1 domain of protein G. We also created a variant of Crotein-G (ZCrotein-G) that contains a potential His₃Cys₁ zinc binding site. At low protein concentrations and in the presence of 20% 2,2,2-trifluoroethanol (TFE) (v/v), the circular dichroism spectra of the designed proteins are distinct from that of 434 Cro and similar to that of the B1 domain of protein G. However, the proteins fail to denature in a cooperative manner. Furthermore, aggregation occurs at moderate protein concentrations or in the absence of TFE. Addition of zinc to ZCrotein-G does not promote structure formation. In summary, 434 Cro has been altered to something that may resemble the B1 domain of protein G, but the protein does not adopt a native structure. Proteins 30:136–143, 1998. © 1998 Wiley-Liss, Inc.     

A novel approach for identifying candidate imprinted genes through sequence analysis of imprinted and control genes

Through the sequence analysis of 27 imprinted human genes and a set of 100 control genes we have developed a novel approach for identifying candidate imprinted genes based on the differences in sequence composition observed. The imprinted genes were found to be associated with significantly reduced numbers of short interspersed transposable element (SINE) Alus and mammalian-wide interspersed repeat (MIR) repeat elements, as previously reported. In addition, a significant association between imprinted genes and increased numbers of low-complexity repeats was also evident. Numbers of the Alu classes AluJ and AluS were found to be significantly depleted in some parts of the flanking regions of imprinted genes. A recent study has proposed that there is active selection against SINE elements in imprinted regions. Alternatively, there may be differences in the rates of insertion of Alu elements. Our study indicates that this difference extends both upstream and downstream of the coding region. This and other consistent differences between the sequence characteristics of imprinted and control genes has enabled us to develop discriminant analysis, which can be used to screen the genome for candidate imprinted genes. We have applied this function to a number of genes whose imprinting status is disputed or uncertain.     

A new approach to sequence comparison: normalized sequence alignment

The Smith-Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology. This ingenious dynamic programming approach was designed to reveal the highly conserved fragments by discarding poorly conserved initial and terminal segments. However, the existing notion of local similarity has a serious flaw: it does not discard poorly conserved intermediate segments. The Smith-Waterman algorithm finds the local alignment with maximal score but it is unable to find local alignment with maximum degree of similarity (e.g. maximal percent of matches). Moreover, there is still no efficient algorithm that answers the following natural question: do two sequences share a (sufficiently long) fragment with more than 70% of similarity? As a result, the local alignment sometimes produces a mosaic of well-conserved fragments artificially connected by poorly-conserved or even unrelated fragments. This may lead to problems in comparison of long genomic sequences and comparative gene prediction as recently pointed out by Zhang et al. (Bioinformatics, 15, 1012-1019, 1999). In this paper we propose a new sequence comparison algorithm (normalized local alignment ) that reports the regions with maximum degree of similarity. The algorithm is based on fractional programming and its running time is O(n2log n). In practice, normalized local alignment is only 3-5 times slower than the standard Smith-Waterman algorithm.     

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     

Los Alamos sequence analysis package for nucleic acids and proteins.

An interactive system for computer analysis of nucleic acid and protein sequences has been developed for the Los Alamos DNA Sequence Database. It provides a convenient way to search or verify various sequence features, e.g., restriction enzyme sites, protein coding frames, and properties of coded proteins. Further, the comprehensive analysis package on a large-scale database can be used for comparative studies on sequence and structural homologies in order to find unnoted information stored in nucleic acid sequences.     

PEPPLOT, a protein secondary structure analysis program for the UWGCG sequence analysis software package.

We describe a program for the analysis of protein secondary structure that operates with the Sequence Analysis Software Package of the University of Wisconsin Genetics Computer Group (UWGCG). The program produces both graphic and printed output. Structure prediction using the Chou and Fasman and Robson et al methods, and hydropathy analysis by the method of Kyte and Doolittle are included along with a simplified method of hydrophobic moment analysis. The power of the program is the coordinated presentation of many different kinds of structural information on the same plot.     

Mapping and navigating mammalian conservation: from analysis to action

Although mammals are often seen as important objects of human interest and affection, many are threatened with extinction. A range of efforts have been proposed and much work has been done to try to conserve mammals, but there is little overall understanding of what has worked and why. As a result, there is no global-scale, coordinated approach to conserving all mammals. Rather, conservation efforts are usually focused at jurisdictional levels where relevant legislation and policies are in force. To help build the framework for a global-scale approach, in this paper we review the many ways that have been proposed for conserving mammals. First, we examine the overall pattern of threat faced by mammals at the global level. Secondly, we look at the major structuring issues in prioritizing and planning mammal conservation, examining in particular the roles of values and scale and a set of approaches to conservation, each of which varies along a continuum. Finally, we lay out the steps necessary to move from planning to implementing mammalian conservation.     

EMBL sequence submission system--an object-oriented approach to developing interactive data collection systems through the WWW

Motivation: To enable a new way of submitting sequence informationto the EMBL nucleotide database through the WWW. This processof data submission is long and complex, and calls for efficientand user-friendly mechanisms for collection and validation ofinformation. Results: Described here is a generic, object-oriented data-submissionsystem that is being used for the EMBL database, but can easilybe tailored to serve several data-submission schemes with arelatively short development and implementation time. The programprovides the user with a friendly interface that breaks thecomplex task into smaller, more manageable tasks and, on theother hand, acts as a pre-filter, scanning errors online. Availability: The program is accessible through the EMBL-EBlWWW server at the URL: http: //www.ebi.ac.uk/subs/ emblsubs.html Contact: E-mail: bshomer{at}ebi.ac.uk     

A friendly statistics package for microarray analysis

SUMMARY: The friendly statistics package for microarray analysis (FSPMA) is a tool that aims to fill the gap between simple to use and powerful analysis. FSPMA is a platform-independent R-package that allows efficient exploration of microarray data without the need for computer programming. Analysis is based on a mixed model ANOVA library (YASMA) that was extended to allow more flexible comparisons and other useful operations like k nearest neighbour imputing and spike-based normalization. Processing is controlled by a definition file that specifies all the steps necessary to derive analysis results from quantified microarray data. In addition to providing analysis without programming, the definition file also serves as exact documentation of all the analysis steps. AVAILABILITY: The library is available under GPL 2 license and, together with additional information, provided at http://www.ccbi.cam.ac.uk/software/psyk/software.html#fspma     

A novel approach to local reliability of sequence alignments

MOTIVATION: The pairwise alignment of biological sequences obtained from an algorithm will in general contain both correct and incorrect parts. Hence, to allow for a valid interpretation of the alignment, the local trustworthiness of the alignment has to be quantified. RESULTS: We present a novel approach that attributes a reliability index to every pair of residues, including gapped regions, in the optimal alignment of two protein sequences. The method is based on a fuzzy recast of the dynamic programming algorithm for sequence alignment in terms of mean field annealing. An extensive evaluation with structural reference alignments not only shows that the probability for a pair of residues to be correctly aligned grows consistently with increasing reliability index, but moreover demonstrates that the value of the reliability index can directly be translated into an estimate of the probability for a correct alignment.