Tomas L. Madden

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The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new(More)
PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been(More)
'BLAST 2 Sequences', a new BLAST-based tool for aligning two protein or nucleotide sequences, is described. While the standard BLAST program is widely used to search for homologous sequences in nucleotide and protein databases, one often needs to compare only two sequences that are already known to be homologous, coming from related species or, e.g.(More)
Protein families often are characterized by conserved sequence patterns or motifs. A researcher frequently wishes to evaluate the significance of a specific pattern within a protein, or to exploit knowledge of known motifs to aid the recognition of greatly diverged but homologous family members. To assist in these efforts, the pattern-hit initiated BLAST(More)
As the rate of DNA sequencing increases, analysis by sequence similarity search will need to become much more efficient in terms of sensitivity, specificity, automation potential, and consistency in annotation. PowerBLAST was developed, in part, to address these problems. PowerBLAST includes a number of options for masking repetitive elements and low(More)
The sequence databases continue to grow at an extraordinary rate. Contributions come from both small laboratories and large-scale projects, such as the Merck EST project. This growth has placed new demands on computational sequence comparison tools such as BLAST. Even now it is no longer practical to evaluate some BLAST reports manually; it is necessary to(More)
The BLAST (Basic Local Alignment Search Tool) family of sequence similarity search programs allows users to input either a nucleotide or amino acid query sequence, and search a nucleotide or amino acid sequence database. The program returns a list of the sequence "hits", alignments to the query sequence, and statistical values. This unit describes how to(More)
The BLAST heuristic algorithm is one of the widely used algorithms for finding similar sequences in sequence databases. The paper acquires importance as traditional approaches to sequence homology searches using BLAST have proven to be too slow to keep up with the current rate of sequence acquisition. The use of the BLAST application on a single processor(More)
Sequence comparison is a basic operation in DNA sequencing projects, and most of sequence comparison methods are based on heuristics, which are fast but not sensitive. The Dynamic Programming Algorithm, Smith-Waterman, obtains the best alignment, but at the expense of computational time. Unfortunately, the inefficiency in the performance of the(More)
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