[ssml] Re: Sequence defined domains?

Dan Bolser dmb at mrc-dunn.cam.ac.uk
Fri Nov 28 05:54:36 EST 2003

Thanks very much for this reply. It sounds very interesting. I think I have to do some
more reading!

One last question though...

Can I ask if you use a partiular sequence similarity matrix to generate multiple
allignments from a single seed, and then develop a profile from that initial multiple
allignment, or if you bootstrap your profile from near identical matches to the seed?

How does the quality of the inital multiple allignment affect the  later developement
of the HMM on a given database?

Is the resulting HMM robust to inital matches (or choice of similarity matrix)?

Above I am talking about itterative profile building, rather than profile searhcing.

Sorry if this question makes no sense,


<quote who="Kevin Karplus">
> The SAM T99 and T2K scripts use an A2M alignment as a seed.  That
> alignment is often a single sequence, but it can be any multiple alignment. Upper
> and lower case letters are used for identifying the alignment columns and
> insertions respectively ("-" is used for a gap in an
> alignment column, and "." may be used to pad insertions).
> If you provide a sequence as a seed that has a large insertion in the middle, the
> constructed HMM will favor having insertions at that
> point, and the target99 or target2k script will (usually) construct a pretty good
> HMM for recognizing the split domain, without any further guidance.
> Occassionally, the target99 or target2k script will have "model drift" in which
> the HMM no longer aligns the initial sequence the way we would want---this causes
> problems in about 1% of the HMMs we build, but may be a bigger problem in
> split-domain HMMs.  The next version of SAM will, I hope, have some new features
> to fix this
> problem (I have some ideas on how to fix it, but am waiting for
> Richard Hughey to implement them, or for a grad student to volunteer to implement
> them).
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