Sequence alignment: Difference between revisions

Revision as of 16:21, 25 August 2023

Revision as of 00:51, 27 August 2023

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In database searches such as BLAST, statistical methods can determine the likelihood of a particular alignment between sequences or sequence regions arising by chance given the size and composition of the database being searched. These values can vary significantly depending on the search space. In particular, the likelihood of finding a given alignment by chance increases if the database consists only of sequences from the same organism as the query sequence. Repetitive sequences in the database or query can also distort both the search results and the assessment of statistical significance; BLAST automatically filters such repetitive sequences in the query to avoid apparent hits that are statistical artifacts.

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 | yeartitle=1996|Computer titleMethods for Macromolecular Sequence Analysis |chapter=&#91;27&#93; Local Alignmentalignment Statisticsstatistics | year=1996| 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>