Measuring Global Credibility with Application to Local Sequence Alignment 英文参考文献.docVIP

MeasuringGlobalCredibilitywithApplicationtoLocal SequenceAlignment Bobbie-JoM.Webb-Robertson1*,LeeAnnMcCue1,CharlesE.Lawrence2 1Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, Washington, United States of America, 2Department of Applied MathematicsandtheCenterofComputationalMolecularBiology,BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica Abstract Computational biology is replete with high-dimensional (high-D) discrete prediction and inference problems, including sequencealignment,RNAstructureprediction,phylogeneticinference,motiffinding,predictionofpathways,andmodel selection problems in statistical genetics. Even though prediction and inference in these settings are uncertain, little attentionhasbeenfocusedonthedevelopmentofglobalmeasuresofuncertainty.Regardlessoftheprocedureemployed to produce a prediction, when a procedure delivers a single answer, that answer is a point estimate selected from the solutionensemble,thesetofallpossiblesolutions.Forhigh-Ddiscretespace,theseensemblesareimmense,andthusthere is considerable uncertainty. We recommend the use of Bayesian credibility limits to describe this uncertainty, where a (12a)%, 0#a#1, credibility limit is the minimum Hamming distance radius of a hyper-sphere containing (12a)% of the posterior distribution. Because sequence alignment is arguably the most extensively used procedure in computational biology, we employ it here to make these general concepts more concrete. The maximum similarity estimator (i.e., the alignmentthatmaximizesthelikelihood)andthecentroidestimator(i.e.,thealignmentthatminimizesthemeanHamming distance from the posterior weighted ensemble of alignments) are used to demonstrate the application of Bayesian credibility limits to alignment estimators. Application of Bayesian credibility limits to the alignment of 20 human/rodent orthologoussequencepairsand125orthologoussequencepairsfromsixShewanellaspeciesshowsthatcredibilitylimitsof theali