FEAST: sensitive local alignment with multiple rates of evolution.
We present a pairwise local aligner, FEAST, which uses two new techniques: a sensitive extension algorithm for identifying homologous subsequences, and a descriptive probabilistic alignment model. We also present a new procedure for training alignment parameters and apply it to the human and mouse genomes, producing a better parameter set for these sequences. Our extension algorithm identifies homologous subsequences by considering all evolutionary histories. It has higher maximum sensitivity than Viterbi extensions, and better balances specificity. We model alignments with several submodels, each with unique statistical properties, describing strongly similar and weakly similar regions of homologous DNA. Training parameters using two submodels produces superior alignments, even when we align with only the parameters from the weaker submodel. Our extension algorithm combined with our new parameter set achieves sensitivity 0.59 on synthetic tests. In contrast, LASTZ with default settings achieves sensitivity 0.35 with the same false positive rate. Using the weak submodel as parameters for LASTZ increases its sensitivity to 0.59 with high error. FEAST is available at http://monod.uwaterloo.ca/feast/.
Hudek
Alexander K
AK
David R. Cheriton School of Computer Science, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada. akhudek@cs.uwaterloo.ca
Brown
Daniel G
DG
D000465:Algorithms; D000818:Animals; D001185:Artificial Intelligence; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D008390:Markov Chains; D051379:Mice; D008957:Models, Genetic; D012372:ROC Curve; D016415:Sequence Alignment / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid; D012984:Software
D004247:DNA