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Should I use framesearch or Blastx?

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Framesearch takes forever; is it worth it?

Framesearch searches a group of protein sequences for similarity to one or more nucleotide query sequences, or searches a group of nucleotide sequences for similarity to one or more protein query sequences. For each sequence comparison, the program finds an optimal alignment between the protein sequence and all possible codons on each strand of the nucleotide sequence. Framesearch uses the Smith-Waterman algorithm, and can insert gaps in the sequence to improve the match.

Two similar programs are Blastx, which searches a protein database against a query nucleotide sequence, or Tblastn and Tfasta, which search a nucleotide database against a query protein sequence. All these programs first translate the nucleotide sequence in all six reading frames before searching and alignment. The Blast group of programs does not insert gaps, and none of these account for frame shift errors that may be present.

But framesearch is very slow, especially when searching an entire database. The blast group of programs will give you a result in half an hour or less , as opposed to 3 hrs or days for framesearch. If you need the sensitivity of framesearch, try running a Blastx/Tblastn/Tfasta search, taking the top scores, and running framesearch against those.

Additional links:

Framesearch sensitivity, from the GCG Newsletter, Nov 95.
Searching databases for sequences similar to a sequence of interest from NYU.