Hello ++ Kevin Karplus-- > > You don't want to compute E-values for > the 4 small searches separately---almost nothing will come up as significant. You > want to combine the scores from the separate searches. You can get a rough > approximation by > saying that the p-value for finding the same sequence from query A and query B is > roughly the product of the p-values (this isn't quite > right, but is probably close enough for your purposes). As you mention this technique, can it be applied to multiple hits from a profile method as the profile is being itteratively developed? I know that traditionally this technique was used for family identification. Basically: the more hits you find to your sequence within one family, the more probable it is that your sequence belongs to that family. The product of the p-values (the 'family probability') has to be corrected for the sequence diversity of your family (to weight down identical hits from identical sequences). Has this been done at the profile-profile level? Cheers Dan.