Nucleic Acids Research, Vol 26, Issue 17 3986-3990, Copyright © 1998 by Oxford University Press
Z Zhang, AA Schaffer, W Miller, TL Madden, DJ Lipman, EV Koonin and SF Altschul
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 (PHI-BLAST)
program described here takes as input both a protein sequence and a pattern
of interest that it contains. PHI-BLAST searches a protein database for
other instances of the input pattern, and uses those found as seeds for the
construction of local alignments to the query sequence. The random
distribution of PHI-BLAST alignment scores is studied analytically and
empirically. In many instances, the program is able to detect statistically
significant similarity between homologous proteins that are not
recognizably related using traditional single-pass database search methods.
PHI-BLAST is applied to the analysis of CED4-like cell death regulators,
HS90-type ATPase domains, archaeal tRNA nucleotidyltransferases and
archaeal homologs of DnaG- type DNA primases.
ARTICLES
Protein sequence similarity searches using patterns as seeds
Department of Computer Science and Engineering, Pennsylvania State University, University Park, PA 16802, USA.
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