Global Alignment of Protein Sequences with Position-Specific Scoring Matrices.

National Library Of Medicine

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Abstract

Current local alignment tools are inherently inappropriate for domain retrieval, because complete domains (by definition) are the units conserved in evolution. Thus, retrieval should compare complete domains to protein subsequences, which is semi-global alignment. Accordingly, we developed a semi-global alignment algorithms and statistics. In previous years, Dr. Sergey Sheetlin implemented our method as a dynamic-programming algorithm in a program called GLOBAL, and Dr. Kann showed GLOBAL's retrieval efficacy is competitive with state-of-the-art tools like HMMer (which is noticeably superior to rps-BLAST). GLOBAL is simple enough to be accelerated by the same heuristics used in local alignment methods like BLAST. Accordingly, Dr. Carroll accelerated GLOBAL using the BLAST word-heuristic, speeding it by about an order of magnitude, making its speed competitive with other domain-retrieval tools. As a first step to incorporating GLOBAL code into various BLAST programs, Dr. Carroll is familiarizing himself with the BLAST codes by applying the TAPk to evaluate variations in BLAST retrieval, as reported in Dr. Spouge's project on the evaluation of retrieval efficacy (LM000094). Results on the PSI-semiGLOBAL tool suggest that it makes a useful tool for detecting domain architectures.