Parametric Alignment of Drosophila Genomes 英文参考文献.docVIP

ParametricAlignmentofDrosophilaGenomes Colin N.Dewey1,Peter M.Huggins2,Kevin Woods2,Bernd Sturmfels2,Lior Pachter2* 1 Department of Electrical Engineering and Computer Sciences, University of California Berkeley, Berkeley, California, United States of America, 2 Department of Mathematics,UniversityofCaliforniaBerkeley,Berkeley,California,UnitedStatesofAmerica TheclassicalgorithmsofNeedleman–WunschandSmith–Watermanfindamaximumaposterioriprobabilityalignment for a pair hidden Markov model (PHMM). To process large genomes that have undergone complex genome rearrangements, almost all existing whole genome alignment methods apply fast heuristics to divide genomes into smallpiecesthataresuitableforNeedleman–Wunschalignment.Inthesealignmentmethods,itisstandardpracticeto fix the parameters and to produce a single alignment for subsequent analysis by biologists. As the number of alignmentprogramsappliedonawholegenomescalecontinuestoincrease,sodoesthedisagreementintheirresults. Thealignmentsproducedbydifferentprogramsvarygreatly,especiallyinnon-codingregionsofeukaryoticgenomes where the biologically correct alignment is hard to find. Parametric alignment is one possible remedy. This methodology resolves the issue of robustness to changes in parameters by finding all optimal alignments for all possible parameters in a PHMM. Our main result is the construction of a whole genome parametric alignment of DrosophilamelanogasterandDrosophilapseudoobscura.Thisalignmentdrawsonexistingheuristicsfordividingwhole genomesintosmallpiecesforalignment,anditreliesonadvanceswehavemadeincomputingconvexpolytopesthat allowustoparametricallyalignnon-codingregionsusingbiologicallyrealisticmodels.Wedemonstratetheutilityof our parametric alignment for biological inference by showing that cis-regulatory elements are more conserved betweenDrosophilamelanogasterandDrosophilapseudoobscurathanpreviouslythought.Wealsoshowhowwhole genome parametric alignment can be used to quantitatively assess the depe