IUBio

Gaps and PAMs

Sean Eddy eddy at boulder.Colorado.EDU
Mon Jun 29 08:17:49 EST 1992


gonnet at inf.ethz.ch (Gaston Gonnet) writes:
>yes, I agree, but with "subjective terms" we cannot do science.  The
>least controversial definition of "significance" is one which relates
>the probability of an homology against the (null hypothesis) probability
>of a random coincidence.  As the model of homology gets more precise,
>or you start including information of other nature (e.g. 3-d structure)
>then the probabilities may be computed differently.  But the definition
>remains the same.

Yes, if you're just trying to decide with two sequences are or are
not likely to be homologous. That's not what your paper is about, though.
You argue that your scoring scheme is "better" than another -- i.e.,
produces "more significant" alignments, presumably. What trustworthy
sequence alignments have you compared the two scoring methods on?

>I am afraid that you
>tend to imply that alignment is "black magic" or "art".  I disagree
>strongly with this view.  We should establish models, compute the
>parameters for these models, verify/reject the models against reality
>and move into better models when the old ones become unsuitable to
>describe reality.  This is the way that science makes progress, not
>with "subjective measures".  There are hundreds of examples of this
>methodology in science.

What "reality" are you going to test, for determining the accuracy
of your methods for aligning distantly similar sequences? Is there
a set of sequences with distantly related sequences but similar
enough 3D structures to permit a confident structure-based alignment?
I'd love to know of one (seriously).

- Sean Eddy
- NeXagen, Inc.
- where RNA is our hammer, and everything looks like a nail
- eddy at shaman.nexagen.com




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