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© IRL Press at Oxford University Press

Improved sensitivity of biological sequence database searches

Douglas L. Brutlag , Jean-Pierre Dautricourt 1, Sunil Maulik 1 and John Relnh 1

Department of Biochemistry, Beckman Center, Stanford University School of Medicine Stanford, CA, 94305
1IntelliGenetics Inc., 700 East E1 Camino Real, Mountain View, CA 94040, USA

We have increased the sensitivity ofDNA and protein sequence database searches by allowing similar but non-identical amino acids or nucleotides to match. In addition, one can match k-tuples or words instead of matching individual residues in order to speed the search. A matching matrix specifies which k-tuples match each other. The matching matrix can be calculated from a similarity matrix of amino acids and a threshold of similarity required for matching. This permits amino acid similarity matrices or replacement matrices (PAM matrices) to be used in the first step of a sequence comparison rather than in a secondary scoring phase. The concept of matching non-identical k-tuples also increases the power ofDNA database searches. For example, a matrix that specifies that any 3-tuple in a DNA sequence can match any other 3-tuple encoding the same amino acid permits a DNA database search using a DNA query sequence for regions that would encode a similar amino acid sequence.

Received on October 10, 1989; accepted on May 1, 1990

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