Editing Sequence analysis (section)

==Profile comparison==
In 1987, Michael Gribskov, Andrew McLachlan, and [[David Eisenberg]] introduced the method of profile comparison for identifying distant similarities between proteins.<ref name="pmid3474607">{{cite journal |author1=Gribskov M |author2=McLachlan AD |author3=Eisenberg D |title=Profile analysis: detection of distantly related proteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=13 |pages=4355–8 |date=July 1987 |pmid=3474607 |pmc=305087 |doi= 10.1073/pnas.84.13.4355|bibcode = 1987PNAS...84.4355G |doi-access=free }}</ref> Rather than using a single sequence, profile methods use a multiple sequence alignment to encode a profile which contains information about the conservation level of each residue. These profiles can then be used to search collections of sequences to find sequences that are related. Profiles are also known as Position Specific Scoring Matrices (PSSMs). In 1993, a probabilistic interpretation of profiles was introduced by [[Anders Krogh]] and colleagues using [[hidden Markov models]].<ref name="pmid7584370">{{cite journal |author1=Brown M |author2=Hughey R |author3=Krogh A |author4=Mian IS |author5=Sjölander K |author6=Haussler D |title=Using Dirichlet mixture priors to derive hidden Markov models for protein families |journal=Proc Int Conf Intell Syst Mol Biol |volume=1 |pages=47–55 |year=1993 |pmid=7584370 }}</ref><ref name="pmid8107089">{{cite journal |author1=Krogh A |author2=Brown M |author3=Mian IS |author4=Sjölander K |author5=Haussler D |title=Hidden Markov models in computational biology. Applications to protein modeling |journal=J. Mol. Biol. |volume=235 |issue=5 |pages=1501–31 |date=February 1994 |pmid=8107089 |doi=10.1006/jmbi.1994.1104 |s2cid=2160404 }}</ref> These models have become known as profile-HMMs.

In recent years,{{When|date=February 2013}} methods have been developed that allow the comparison of profiles directly to each other. These are known as profile-profile comparison methods.<ref name="pmid21998158">{{cite journal |author1=Ye X |author2=Wang G |author3=Altschul SF |title=An assessment of substitution scores for protein profile-profile comparison |journal=Bioinformatics |volume=27 |issue=24 |pages=3356–63 |date=December 2011 |pmid=21998158 |doi=10.1093/bioinformatics/btr565 |pmc=3232366}}</ref>