Improved pairwise alignment of genomic dna

Abstract

Graduate School iii Advances in DNA sequencing technology have fueled a rapid increase in the number of sequenced vertebrate genomes, and we anticipate an explosion in the number of genomes sequenced in the near future. Detecting similarities between genomes is a valuable technique in discovering functional elements, and sequence alignment is the primary tool for discovering similarities. The quality of alignments is affected by several user-specified control parameters. The parameters are so little understood that most users simply use default settings. We seek to change that, to have the program automatically infer appropriate parameter choices from statistics derived automatically from the sequences. We introduce a program, INFERZ, which addresses part of the inference problem, inferring substitution and gap scores according to a mathematically sound model. Further, we explore the usefulness of iterating inferred scores to convergence. We test this process on both simulated and actual genomic data, and show that iteration will converge in