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Efficient algorithms for analyzing segmental duplications with deletions and inversions in genomes.doc

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Efficient algorithms for analyzing segmental duplications with deletions and inversions in genomes

Kahnetal.AlgorithmsforMolecularBiology2010,5:11 /content/5/1/11 RESEARCH OpenAccess Efficientalgorithmsforanalyzingsegmental duplicationswithdeletionsandinversionsin genomes CrystalLKahn1*,ShayMozes1*,BenjaminJRaphael1,2* Abstract Background:Segmentalduplications,orlow-copyrepeats,arecommoninmammaliangenomes.Inthehuman genome,mostsegmentalduplicationsaremosaicscomprisedofmultipleduplicatedfragments.Thiscomplex genomicorganizationcomplicatesanalysisoftheevolutionaryhistoryofthesesequences.Onemodelproposedto explainthismosaicpatternsisamodelofrepeatedaggregationandsubsequentduplicationofgenomic sequences. Results:Wedescribeapolynomial-timeexactalgorithmtocomputeduplicationdistance,agenomicdistance definedasthemostparsimoniouswaytobuildatargetstringbyrepeatedlycopyingsubstringsofafixedsource string.Thisdistancemodelstheprocessofrepeatedaggregationandduplication.Wealsodescribeextensionsof thisdistancetoincludecertaintypesofsubstringdeletionsandinversions.Finally,weprovideadescriptionofa sequenceofduplicationeventsasacontext-freegrammar(CFG). Conclusion:Thesenewgenomicdistanceswillpermitmorebiologicallyrealisticanalysesofsegmental duplicationsingenomes. Introduction maketheunderlyingcomputationalproblemsmoredif- Genomesevolveviamanytypesofmutationsrangingin ficult.Forinstance,computingreversaldistanceingen- scalefromsinglenucleotidemutationstolargegenome omeswith duplicated segments isNP-hard [3]. Models rearrangements. Computational models of these muta- thatincludebothduplicationsandothertypesofmuta- tional processes allow researchers to derive similarity tions - such as inversions - often result in similarity measuresbetweengenomesequencesandtoreconstruct measures that cannot be computed efficiently. Thus, evolutionaryrelationshipsbetweengenomes.Forexam- mostcurrentapproachesforduplicationanalysisrelyon ple, considering chromosomal inversions as the only heuristics,approximationalgorithms,orrestrictedmod- typeofmutationleadstotheso-calledrevers