Gaps and PAMs

goldman at mbcl.rutgers.edu goldman at mbcl.rutgers.edu
Wed Jul 1 14:36:22 EST 1992

In article <1992Jun29.165400.23251 at bas-a.bcc.ac.uk>, ucbcdtj at ucl.ac.uk (David T Jones) writes:
> 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.
> Alignments can be significant and yet be wrong. 
I agree 100%

. large deletion to save net.bandwidth..

> I don't think alignment technology has reached a point where an
> automatic procedure can take as input an entire protein sequence
> databank and generate as output a complete set of accurately aligned protein
> sequence families. The alignments may well be statistically significant,
> and may well look highly plausible, but these observations alone cannot
> guarantee the correctness of alignments.
One only has to look (has someone made this point already?) at the
recently-published yeast chromosome.  They found similarities for only a small
percentage of their ORFs but I would be prepared to bet that the  structures of
many, if not most, of the longer ORFs will turn out to be related to
already-solved structures.

               Adrian Goldman

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