Fellow bio-soft netters -
I thought you might be interested in a communication that I was involved in
last week. Tom Doak (herricklab at bioscience.utah.edu) wrote me the following
query:
>>...I've been using Profiles in the GCG package quite a bit, so checked out
>>internet (a new toy to me, that I'm not really familier with yet) exchanges
>>on that subject, and it sounded as if you might be able to help, or at least
>>lead me in the right direction. You asked if there were ways to compare
>>profiles, a question I have also had, and I was hoping you had had usefull
>>response that could be passed along. The two things I would like to be able
>>to do are to 1) independently build profiles for two different families,
>>that I claim to be related subfamilies, then show that thier profiles are in
>>fact the same, at some confidence level. 2) Know when I have added enough
>>members into the alignment I'm making my profile from, because the profile
>>hasn't changed 'signifigantly' from one to the next; you can imagine some sort
>>of plot leveling off at some point. Also, as long as I'm rambling, I've been
>>doing most of my alignments with GCG Pileup, and have found that it gives
>>'visually' correct alignments, anything good or bad you could say about it?...
And I replied to him:
>....Last year when I was posing questions to the net concerning profile
>comparisons Roland Luethy offered the most concrete solution. He had
>written a profile alignment algorithm back when he was working in
>Eisenberg's lab with Gribskov which operates within the GCG environment to
>create a new, merged profile and a consensus alignment from two previous
>profiles. It works rather well and I'm sure he would be happy to send it off
>to you also.
>His e-mail address, as of April 1992, is "rluethy at ulrec2.unil.ch".
>Unfortunately it does not adequately address your points:
>Even though his program does produce a new profile from preexisting, related
>profiles, it does not give any indication, statistically, of "how well" the
>two input profiles compared to each other---it is still a subjective call.
>I suppose one could then ProfileSearch with the new profile and evaluate "z"
>scores of the hits from each of the two families' members.
>Being able to ascertain when enough members are in an alignment would be
>very handy, and, I do agree, one does reach a "point of diminishing returns"
>upon the addition of sequences to an alignment. What we need is some "hot"
>statatician to get involved in this area and produce a nice set of auxillary
>programs which would interpret and analyze profile data and produce nice
>graphical output easily understood by us biology types, all within the GCG
>environment. The whole idea of "how good" is this profile, the "quality" of
>validation, needs to be addressed in a more quantitative and less subjective
>manner as well as the significance of search hits.
Call for help in the area; are there any stat' people listening? :^) !!
>I also like PileUp and have found that of the standard multiple sequence
>alignment programs it and ClustAl seem to do the best jobs, especially if the
>sequences being aligned ARE fairly homologous along their entire lengths. I
>believe many individuals in the area would tend to agree with this statement.
>PIMA also has very strong advantages, especially in highly divergent sequences
>where only patches of homology remain. Unfortunately it does not operate in a
>VMS environment.
Take-home message!!:
>However, in ALL cases careful, subjective and biological evaluation of the
>resultant alignments should be undertaken and, if deemed necessary, the
>alignments should be modified by hand.
Back to software discussion:
>MAlignEd is particularly good at this editing process and can help one to
>decide which adjustments to make in the alignment based on its highlighting
>mode....
Thought you might be interested, Steve Thompson
Steven M. Thompson
Consultant in Molecular Genetics and Sequence Analysis
VADMS (Visualization, Analysis & Design in the Molecular Sciences) Laboratory
Washington State University, Pullman, WA 99164-1224, USA
AT&Tnet: (509) 335-0533 or 335-3179 FAX: (509) 335-0540
BITnet: THOMPSON at WSUVMS1 or STEVET at WSUVM1
INTERnet: THOMPSON at wsuvms1.csc.wsu.edu
