A set of Macintosh computer programs for the design and analysis of synthetic genes

Computer programs that can be used for the design of synthetic genes and that are run on an Apple Macintosh computer are described. These programs determine nucleic acid sequences encoding amino acid sequences. They select DNA sequences based on codon usage as specified by the user, and determine the placement of base changes that can be used to create restriction enzyme sites without altering the amino acid sequence. A new algorithm for finding restriction sites by translating the restriction endonuclease target sequence in all three reading frames and then searching the given peptide or protein amino acid sequence with these short restriction enzyme peptide sequences is described. Examples are given for the creation of synthetic DNA sequences for the bovine prethrombin-2 and ribonuclease A genes.     

Software Tools for DNA Sequence Design

The design of DNA sequences is a key problem for implementing molecular self-assembly with nucleic acid molecules. These molecules must meet several physical, chemical and logical requirements, mainly to avoid mishybridization. Since manual selection of proper sequences is too time-consuming for more than a handful of molecules, the aid of computer programs is advisable. In this paper two software tools for designing DNA sequences are presented, the DNASequenceGenerator and the DNASequenceCompiler. Both employ an approach of sequence dissimilarity based on the uniqueness of overlapping subsequences and a graph based algorithm for sequence generation. Other sequence properties like melting temperature or forbidden subsequences are also regarded, but not secondary structure errors or equilibrium chemistry. Fields of application are DNA computing and DNA-based nanotechnology. In the second part of this paper, sequences generated with the DNASequenceGenerator are compared to those from several publications of other groups, an example application for the DNASequenceCompiler is presented, and the advantages and disadvantages of the presented approach are discussed.     

DNA一级序列不同编码方法和相似度比较

为了DNA一级序列的相似度计算,本文比较了三种编码方案:单一碱基在DNA序列中的相对位置、二联码即相邻二碱基在序列中的相对位置、编序单一碱基在DNA序列中的相对位置和二联码在序列中的编序相对位置,在此基础上,运用分子连接性指数计算得到序列的不变量,进而,由塔尼莫特法计算得到物种间的相似度。由单一碱基在DNA序列中的相对位置法比较相似度,对于本研究中10个物种,得到了与生物进化树非常相一致的结果。     

Pattern matching of biological sequences with limited storage

Existing methods for getting the locally best matched alignments between a pair of biological sequences require O(N2) computational steps and O(N2) storage, where N is the average sequence length. An improved method is presented with which the storage requirement is greatly reduced, while the computational steps remain O(N2). Only a small number of additional steps are required to display any common sub-sequences with similarity scores greater than a given threshold. The aligments found by the algorithm are optimal in the sense that their scores are locally maximal, where each score is a sum of weights given to individual matches/replacements, insertions and deletions involved in the alignment. The algorithm was implemented in C programming language on a personal computer. Data area of 64 kbytes on random access memory and a few hundred kbytes on a disk is sufficient for comparing two protein or nucleic acid sequences of 2500 residues. The programs are particularly valuable when used in combination with fast sequence search programs.     

EMBLSCAN: fast approximate DNA database searches on compact disc.

An algorithm that allows rapid searching of nucleic acid sequences based on pregenerated index files is described. The programs and index files for searching the entire EMBL nucleotide sequence collection are being distributed on the EMBL Data Library's CD-ROM.     

An improved algorithm for nucleic acid secondary structure display

An improved algorithm for the display of nucleic acid secondary structures is presented. It is particularly suitable for large sequence segments and it automatically generates an aesthetically pleasing display of the structure with very limited overlap of strands. Structural similarities in different structures are conserved in the display thus greatly aiding structural homology comparisons. Using the algorithm, we illustrate the effect of ribosome translocation on the secondary structure of a rat neuropeptide messenger RNA.     

DNA Translator and Aligner: HyperCard utilities to aid phylogenetic analysis of molecules.

DNA Translator and Aligner are molecular phylogenetics HyperCard stacks for Macintosh computers. They manipulate sequence data to provide graphical gene mapping, conversions, translations and manual multiple-sequence alignment editing. DNA Translator is able to convert documented GenBank or EMBL documented sequences into linearized, rescalable gene maps whose gene sequences are extractable by clicking on the corresponding map button or by selection from a scrolling list. Provided gene maps, complete with extractable sequences, consist of nine metazoan, one yeast, and one ciliate mitochondrial DNAs and three green plant chloroplast DNAs. Single or multiple sequences can be manipulated to aid in phylogenetic analysis. Sequences can be translated between nucleic acids and proteins in either direction with flexible support of alternate genetic codes and ambiguous nucleotide symbols. Multiple aligned sequence output from diverse sources can be converted to Nexus, Hennig86 or PHYLIP format for subsequent phylogenetic analysis. Input or output alignments can be examined with Aligner, a convenient accessory stack included in the DNA Translator package. Aligner is an editor for the manual alignment of up to 100 sequences that toggles between display of matched characters and normal unmatched sequences. DNA Translator also generates graphic displays of amino acid coding and codon usage frequency relative to all other, or only synonymous, codons for approximately 70 select organism-organelle combinations. Codon usage data is compatible with spreadsheet or UWGCG formats for incorporation of additional molecules of interest. The complete package is available via anonymous ftp and is free for non-commercial uses.     

DNA计算中核酸序列设计方法比较研究(英文)

DNA计算是将现实问题进行编码,映射到DNA分子上,然后通过分子生物实验产生出代表问题解的DNA分子,最后通过检测技术提取出该DNA分子．高质量的DNA编码可以尽可能避免或减少计算过程中出现的错误,并使检测阶段易于提取出代表问题解的DNA分子．文中对基于汉明距离和基于自由能的DNA核酸编码方法进行研究,分析了两类方法的约束条件对DNA编码质量的影响,比较了两类方法排除非特异性杂交的完备性和计算量,进一步分析了两类方法编码DNA序列的效率．通过分析和比较得到,两类DNA计算编码方法都能有效地限制DNA分子间的非特异性杂交,其中基于汉明距离的DNA编码方法的计算量比较小,但是它仅能近似地估计DNA分子间杂交的热力学稳定性,不能完全替代最小自由能的编码方法．在满足DNA计算试验精度要求的条件下,采用基于汉明距离的DNA编码设计方法不仅能有效地的挑选出特异性杂交和非特异性杂交的DNA序列,还能有效地减少计算量,从而提高DNA序列设计的效率．     

Two computer programs for rapid entry of DNA sequence data

Two computer programs for the IBM personal computer are described for rapid and accurate entry of DNA sequence data. The DNA sequence files produced can be used directly by the DNA sequence manipulation programs by R.Staden (the DataBase system), the University of Wisconsin Genetics Computer Group, DNASTAR, or D.Mount. The first program, DIGISEQ, utilizes a sonic digitizer for semi-automation of sequence entry. To enter the DNA sequence each band of a gel 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-entering the centers of the lanes. The second program, TYPESEQ, uses only the keyboard for input. The keyboard is reconfigured to place nucleotides and ambiguity codes under the fingers of one hand, corresponding to the order of the nucleotides on the gel defined by the user. Both programs produce individual tones for each nucleotide, and certain ambiguity codes. This verifies input of the correct nucleotide or ambiguity code, and thus eliminates the need to visually check the screen display during sequence entry.     

The GenBank nucleic acid sequence database

The GenBank nucleic acid sequence database is a computer-based collection of all published DNA and RNA sequences; it contains over five million bases in close to six thousand sequence entries drawn from four thousand five hundred published articles. Each sequence is accompanied by relevant biological annotation. The database is available either on magnetic tape, on floppy diskettes, on-line or in hardcopy form. We discuss the structure of the database, the extent of the data and the implications of the database for research on nucleic acids.     

Computational gene identification: an open problem

As the Human Genome Project enters the large-scale sequencing phase, computational gene identification methods are becoming essential for the automatic analysis and annotation of large uncharacterized genomic sequences. Currently available computer programs relying mainly on sequence coding statistics are of great use in pin-pointing regions in genomic sequences containing exons. Such programs perform rather poorly, however, when the problem is to fully elucidate gene structure. For this problem, the DNA sequence signals involved in the specification of the genes—start sites and splice sites—carry a lot of information, and simple methods relying on such information can predict gene structure with an accuracy to some extent comparable to that of other more sophisticated computational methods.     

Hypercard-based data management tools for molecular biologists.

I have designed a Macintosh data management system for molecular biologists. This system, called DataMinder, can be used to store information about oligonucleotides, nucleic acid or protein sequences, recombinant DNA clones, cells, reagents and protocols. DataMinder is not limited to data storage. A number of utilities for data analysis are provided, including those for the evaluation of oligonucleotides for use as hybridization probes or primers for DNA synthesis, and a variety of sequence editing features. Context-sensitive help is available on-line. DataMinder is simple to use and to customize and allows for sharing of database information across a computer network.     

Recognition of ill-defined signals in nucleic acid sequences

A set of programs has been developed for the definition and handling of nucleic acid sequence consensus information. The sequences of known genetic control signals are combined in a matrix. The origins and positions of the signals are recorded. Old matrices can be updated dynamically: new signals are included and obsolete ones deleted. Matrices of several different types are computed optionally. Several of these matrices can be combined to find possible new signals. The use of matrices allows the exact quantification of signal qualities. The described programs are part of a program library named GENEXPERT. Application examples given are the search for tRNA genes and the search for promoters in the bacteriophage lambda genome.     

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

AUGUR is a program to predict, display and analyze the three-dimensional structure of B-DNA. The user can choose one of six models to predict the helical parameters of a given sequence. These parameters are then used to generate the coordinates of the DNA model in three-dimensional space (trajectory). The trajectory can be displayed and rotated on a graphics terminal. The trajectory and helical parameters can also be searched for bends and structural homologues.     

ACNUC--a portable retrieval system for nucleic acid sequence databases: logical and physical designs and usage

ACNUC is a database structure and retrieval software for use with either the GenBank or EMBL nucleic acid sequence data collections. The nucleotide and textual data furnished by both collections are each restructured into a database that allows sequence retrieval on a multi-criterion basis. The main selection criteria are: species (or higher order taxon), keyword, reference, journal, author, and organelle; all logical combinations of these criteria can be used. Direct access to sequence regions that code for a specific product (protein, tRNA or rRNA) is provided. A versatile extraction procedure copies selected sequences, or fragments of them, from the database to user files suitable to be analysed by user-supplied application programs. A detailed help mechanism is provided to aid the user at any time during the retrieval session. All software has been written in FORTRAN 77 which guarantees a high degree of transportability to minicomputers or mainframes.     

基于代理程序开发核酸序列二次数据库

以构建核酸序列二次数据库为目的,基于Windows操作系统下,编译Web代理程序,介绍开发核酸序列二次数据库的一般过程。研究通用代理程序开发本地化核酸序列二次数据库的具体步骤,所涉及的关键技术以及常见问题解决。解决了生物信息数据繁多与数据处理工作量大问题,经反复调试基本实现了示例程序核酸序列二级数据库系统的构建。     

CORGEN: a FORTRAN-77 generator of standard and non-standard DNA helices from the sequence

An analytical procedure CORGEN generates a variety of DNA double-stranded structures from user-supplied sequence using a nucleic acid database incorporated into a standard FORTRAN-77 program. Alternatively, the cylindrical polar coordinates of DNA components may be supplied from the external table. An algorithm that performs intercalation sites in DNA is described. This procedure can be used to generate complexes of antibiotics with DNA. Non-standard DNA structures can be built by alternating the global helical twist and global helical rise in the regular DNA helix. The procedures described can be used for computer generation of a variety of non-standard DNA structures which can be subjected to molecular mechanics and dynamics simulations.     

An improved human display model for occupant crash simulation programs

Presented is an improved three-dimensional display model of a human being which can be used to display the results of three-dimensional simulation programs that predict the positions of an occupant during impact of a vehicle. The model allows the user to view the occupant from any orientation in any position during the crash. The display model assumes the usual break up of the body into rigid segments, which is normal for occupant-crash simulation programs, but the shape of the segments in the display model are not necessarily the same as those used in the crash simulation. The display model is proportioned so as to produce a realistic drawing of the human body in any position. Joints connecting the seqments are also drawn to improve realism.     

A novel method for alignment of two nucleic acid sequences using ant colony optimization and genetic algorithms

We describe a new method for pairwise nucleic acid sequence alignment that can also be used for pattern searching and tandem repeat searching within a nucleic acid sequence. The method is broadly a hybrid algorithm employing ant colony optimization (ACO) and the simple genetic algorithm. The method first employs ACO to obtain a set of alignments, which are then further processed by an elitist genetic algorithm, which employs primitive selection and a novel multipoint crossover-mutation operator to generate accurate alignments. The resulting alignments show a fair amount of accuracy for smaller and medium size sequences. Furthermore, this algorithm can be used rather quickly and efficiently for aligning shorter sequences and also for pattern searching in both nucleic acid and amino acid sequences. Furthermore, it can be used as an effective local alignment method or as a global alignment tool. On improvement of accuracy, this method can be extended for use towards multiple sequence alignment.