Compressed amino acid alphabets

A compressed alphabet uses one letter to represent a group of similar amino acids. For example, F might be used for F, Y and W. The advantage of using a compressed alphabet is that some of the most common substitutions (e.g., F for W or L for V) are tolerated without losing the exact matches required for word indexing. This improvement in sensitivity because matching words are found in more distantly-related sequences. A significant (so far, mostly unpublished) research effort was invested to determine the optimal alphabet and pattern for typical medium- to low-identity protein searches.

Compressed amino acid alphabets are supported for all search and clustering commands that use indexes (see index options). The alphabet can be specified using the -alpha option. The alphabet is specified as a string containing every letter in the standard 20-letter amino acid alphabet exactly once. Groups of letters that are to be represented by a single symbol in the reduced alphabet are separated by commas.

The order the groups are specified is not significant. By convention, the group is represented by its first letter, so for example in the above alphabet the 4-mer MARW would be compressed to IAKF.

By default, protein ublast is the only command that uses compressed alphabets. This is because other commands are generally used for high-identity search and clustering tasks where compressed alphabets typically give only a marginal improvement in sensitivity.

Example
The default compressed alphabet and pattern for protein ublast could be specified by the following options:

-alpha A,KR,DENQ,C,G,H,ILVM,FYW,P,ST -pattern 10111011