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}}</ref> A variety of computational algorithms have been applied to the sequence alignment problem. These include slow but formally correct methods like [[dynamic programming]]. These also include efficient, [[heuristic algorithm]]s or [[probability|probabilistic]] methods designed for large-scale database search, that do not guarantee to find best matches.
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Methods of statistical significance estimation for gapped sequence alignments are available in the literature.<ref name="ortet"/><ref name=altschul>{{cite book|author1=Altschul SF |author2=Gish W | year=1996| title=Local Alignment Statistics| journal= Meth.Enz. | volume=266 | pages = 460–480|doi=10.1016/S0076-6879(96)66029-7|pmid=8743700 |series=Methods in Enzymology|isbn=9780121821678}}</ref><ref name=hartmann>{{cite journal| author=Hartmann AK| year=2002| title=Sampling rare events: statistics of local sequence alignments|
journal= Phys. Rev. E| volume=65| page=056102|doi=10.1103/PhysRevE.65.056102| pmid=12059642| issue=5|arxiv=cond-mat/0108201|bibcode=2002PhRvE..65e6102H| s2cid=193085| url=https://www.semanticscholar.org/paper/bedd73ed63f6f8ea1985360f0d725630fe0f3fc3}}</ref><ref name=newberg>{{cite journal| author=Newberg LA | year=2008 | title=Significance of gapped sequence alignments | journal= J Comput Biol| volume=15| pages=1187–1194 | pmid = 18973434 | doi=10.1089/cmb.2008.0125| issue=9| pmc=2737730}}</ref><ref name=eddy>{{cite journal| author=Eddy SR| year=2008 | title=A probabilistic model of local sequence alignment that simplifies statistical significance estimation | journal= PLOS Comput Biol | volume=4| editor1-first=Burkhard| pages=e1000069 | pmid = 18516236| editor1-last=Rost | doi=10.1371/journal.pcbi.1000069| issue=5| pmc=2396288| last2=Rost| first2=Burkhard| bibcode=2008PLSCB...4E0069E| s2cid=15640896 | doi-access=free }}</ref><ref name=bastien>{{cite journal|author1=Bastien O |author2=Aude JC |author3=Roy S |author4=Marechal E | year=2004 | title=Fundamentals of massive automatic pairwise alignments of protein sequences: theoretical significance of Z-value statistics | journal= Bioinformatics | volume=20| issue=4| pages=534–537| pmid = 14990449| doi = 10.1093/bioinformatics/btg440 | doi-access=free }}</ref><ref name=agrawal11>{{cite journal|author1=Agrawal A |author2=Huang X | year=2011| title=Pairwise Statistical Significance of Local Sequence Alignment Using Sequence-Specific and Position-Specific Substitution Matrices|journal= IEEE/ACM Transactions on Computational Biology and Bioinformatics| volume=8| pages=194–205|doi=10.1109/TCBB.2009.69|pmid=21071807 | issue=1|s2cid=6559731 |url=https://www.semanticscholar.org/paper/765f9333d5af7274c0a44b39407f78c1dcdfab0f }}</ref><ref name=agrawal08>{{cite journal| author1=Agrawal A| author2=Brendel VP| author3=Huang X| year=2008| title=Pairwise statistical significance and empirical determination of effective gap opening penalties for protein local sequence alignment| journal=International Journal of Computational Biology and Drug Design| volume=1| pages=347–367| doi=10.1504/IJCBDD.2008.022207| pmid=20063463| url=http://inderscience.metapress.com/content/1558538106522500/| issue=4| url-status=dead| archive-url=https://archive.today/20130128163812/http://inderscience.metapress.com/content/1558538106522500/| archive-date=28 January 2013| df=dmy-all}}</ref>
===Assessment of credibility===
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==Non-biological uses==
The methods used for biological sequence alignment have also found applications in other fields, most notably in [[natural language processing]] and in [[Sequence analysis in social sciences|social sciences]], where the [[Needleman-Wunsch algorithm]] is usually referred to as [[Optimal matching]].<ref>{{cite journal|author1=Abbott A. |author2=Tsay A. | year=2000 | title=Sequence Analysis and Optimal Matching Methods in Sociology, Review and Prospect | journal=Sociological Methods and Research | volume=29|issue=1 | pages=3–33 | doi=10.1177/0049124100029001001|s2cid=121097811 }}</ref> Techniques that generate the set of elements from which words will be selected in natural-language generation algorithms have borrowed multiple sequence alignment techniques from bioinformatics to produce linguistic versions of computer-generated mathematical proofs.<ref name=Barzilay>{{cite
==Software==
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