[Computational-biology] Re: Point Specific Mutation Matrix vs. profile HMM ?

Michael Spitzer professa at gmx.net
Sun Feb 12 16:19:31 EST 2006


Hi,

On Sun, 12 Feb 2006 15:40:08 +0100, harald <please_noSpam at gmx.de>
wrote:

> [...] I can not see a big difference between the Point 
> Specific Mutation Matrix which is used by PSI-BLAST and the profile HMM 
> used by HMMER, except the possibility to compute a profile from 
> unaligned sequences in the case of the profile HMM.

There are two papers (I know of) that compare profile HMMs and
PSI-BLAST quite nicely:

Park J, Karplus K, Barrett C, Hughey R, Haussler D, Hubbard T, Chothia
C. Sequence comparisons using multiple sequences detect three times as
many remote homologues as pairwise methods. J Mol Biol. 1998 284(4):
1201-1210

Madera M, Gough J. A comparison of profile hidden Markov model
procedures for remote homology detection. Nucleic Acids Res. 2002
30(19): 4321-4328

Both conclude (more or less) that profile HMMs retrieve approx. 10%
more true homologs than PSI-BLAST. The main (and only?) disadvantages
of profile HMMs seem to be higher computational cost and a less solid
statistical theory corresponding to E-value calculation, compared to
PSI-BLAST. The latter may have changed by now, but I'm not aware of
current publications on this at the moment.

HTH, Micha



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