Alignments without low-scoring regions

Given a strong match be%een regions of txvo sequences, horn far can the match be meaningfully extended if gaps are all04 in the resdtinrc aknment? The aim is to aviod sear&ix bwond the point th asuseful extension of the a&mm& is l&ly to be found. Without loss of generality, we can restrict attention to the suffixes of the sequences that follow the strong match, which leads to the following formal problem. Given two sequences and a fixed X > 0, align initial portions of the sequences subject to the constraint that no section of the alignment scores below -X. Our results indicate that computing an optimal alignment under this constraint is very expensive. However, less rigorous conditions on the alignment can be guaranked by quite eiiicient algorithms. One of these variants has been implemented in a new release of the Blast suite of database search programs. a b C Figure 1: Graph model of a simple alignment problem. Dark edges (corresponding to aligning identical letters) score 1, and all other edges score -1.