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D J Lipman

Publications and source records attributed to D J Lipman.

10 recordsLinked to original sources
PubMed1991

Modelling neutral and selective evolution of protein folding.

We examine a model evolutionary space consisting of genotypes mapped to their corresponding phenotypes. This mapping is derived from a lattice model for proteins which, despite its highly idealized nature, has been shown to share general properties with real proteins. Large evolutionary networks are observed, with genotypes corresponding to non-lethal phenotypes linked by unit mutational steps. Neutral mutations are necessary for traversing the evolutionary networks, and even one neutral mutation in a genotype can change the phenotypes attainable by a unit mutational step.

Biological Evolution↗
PubMed1991

A workbench for multiple alignment construction and analysis.

Multiple sequence alignment can be a useful technique for studying molecular evolution, as well as for analyzing relationships between structure or function and primary sequence. We have developed for this purpose an interactive program, MACAW (Multiple Alignment Construction and Analysis Workbench), that allows the user to construct multiple alignments by locating, analyzing, editing, and combining "blocks" of aligned sequence segments. MACAW incorporates several novel features. (1) Regions of local similarity are located by a new search algorithm that avoids many of the limitations of previous techniques. (2) The statistical significance of blocks of similarity is evaluated using a recently developed mathematical theory. (3) Candidate blocks may be evaluated for potential inclusion in a multiple alignment using a variety of visualization tools. (4) A user interface permits each block to be edited by moving its boundaries or by eliminating particular segments, and blocks may be linked to form a composite multiple alignment. No completely automatic program is likely to deal effectively with all the complexities of the multiple alignment problem; by combining a powerful similarity search algorithm with flexible editing, analysis and display tools, MACAW allows the alignment strategy to be tailored to the problem at hand.

Algorithms↗
PubMed1990

Equal animals.

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Animals↗
PubMed1990

Basic local alignment search tool.

A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.

Algorithms↗
PubMed1990

Protein database searches for multiple alignments.

Protein database searches frequently can reveal biologically significant sequence relationships useful in understanding structure and function. Weak but meaningful sequence patterns can be obscured, however, by other similarities due only to chance. By searching a database for multiple as opposed to pairwise alignments, distant relationships are much more easily distinguished from background noise. Recent statistical results permit the power of this approach to be analyzed. Given a typical query sequence, an algorithm described here permits the current protein database to be searched for three-sequence alignments in less than 4 min. Such searches have revealed a variety of subtle relationships that pairwise search methods would be unable to detect.

Algorithms↗
PubMed1989

Weights for data related by a tree.

How can one characterize a set of data collected from different biological species, or indeed any set of data related by an evolutionary tree? The structure imposed by the tree implies that the data are not independent, and for most applications this should be taken into account. We describe strategies for weighting the data that circumvent some of the problems of dependency.

Animals↗
PubMed1989

A tool for multiple sequence alignment.

Multiple sequence alignment can be a useful technique for studying molecular evolution and analyzing sequence-structure relationships. Until recently, it has been impractical to apply dynamic programming, the most widely accepted method for producing pairwise alignments, to comparisons of more than three sequences. We describe the design and application of a tool for multiple alignment of amino acid sequences that implements a new algorithm that greatly reduces the computational demands of dynamic programming. This tool is able to align in reasonable time as many as eight sequences the length of an average protein.

Algorithms↗
PubMed1988

Improved tools for biological sequence comparison.

We have developed three computer programs for comparisons of protein and DNA sequences. They can be used to search sequence data bases, evaluate similarity scores, and identify periodic structures based on local sequence similarity. The FASTA program is a more sensitive derivative of the FASTP program, which can be used to search protein or DNA sequence data bases and can compare a protein sequence to a DNA sequence data base by translating the DNA data base as it is searched. FASTA includes an additional step in the calculation of the initial pairwise similarity score that allows multiple regions of similarity to be joined to increase the score of related sequences. The RDF2 program can be used to evaluate the significance of similarity scores using a shuffling method that preserves local sequence composition. The LFASTA program can display all the regions of local similarity between two sequences with scores greater than a threshold, using the same scoring parameters and a similar alignment algorithm; these local similarities can be displayed as a "graphic matrix" plot or as individual alignments. In addition, these programs have been generalized to allow comparison of DNA or protein sequences based on a variety of alternative scoring matrices.

Amino Acid Sequence↗
PubMed1985

Rapid and sensitive protein similarity searches.

An algorithm was developed which facilitates the search for similarities between newly determined amino acid sequences and sequences already available in databases. Because of the algorithm's efficiency on many microcomputers, sensitive protein database searches may now become a routine procedure for molecular biologists. The method efficiently identifies regions of similar sequence and then scores the aligned identical and differing residues in those regions by means of an amino acid replacability matrix. This matrix increases sensitivity by giving high scores to those amino acid replacements which occur frequently in evolution. The algorithm has been implemented in a computer program designed to search protein databases very rapidly. For example, comparison of a 200-amino-acid sequence to the 500,000 residues in the National Biomedical Research Foundation library would take less than 2 minutes on a minicomputer, and less than 10 minutes on a microcomputer (IBM PC).

Amino Acid Sequence↗