Position Specific Iterative BLAST (PSI-BLAST)


The blastpgp program can do an iterative search in which sequences found in one round of searching are used to build a score model for the next round of searching. In this usage, the program is called Position-Specific Iterated BLAST, or PSI-BLAST. As explained in the accompanying paper, the BLAST algorithm is not tied to a specific score matrix. Traditionally, it has been implemented using an AxA substitution matrix where A is the alphabet size. PSI-BLAST instead uses a QxA matrix, where Q is the length of the query sequence; at each position the cost of a letter depends on the position w.r.t. the query and the letter in the subject sequence.

The position-specific matrix for round i+1 is built from a constrained multiple alignment among the query and the sequences found with sufficiently low e-value in round i. The top part of the output for each round distinguishes the sequences into: sequences found previously and used in the score model, and sequences not used in the score model. The output currently includes lots of diagnostics requested by users at NCBI. To skip quickly from the output of one round to the next, search for the string "producing", which is part of the header for each round and likely does not appear elsewhere in the output. PSI-BLAST "converges" and stops if all sequences found at round i+1 below the e-value threshold were already in the model at the beginning of the round.