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. 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).

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Support Year
11
Fiscal Year
2014
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Indirect Cost
Name
National Library of Medicine
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Carroll, Hyrum D; Williams, Alex C; Davis, Anthony G et al. (2015) Improving Retrieval Efficacy of Homology Searches Using the False Discovery Rate. IEEE/ACM Trans Comput Biol Bioinform 12:531-7
Frith, Martin C; Park, Yonil; Sheetlin, Sergey L et al. (2008) The whole alignment and nothing but the alignment: the problem of spurious alignment flanks. Nucleic Acids Res 36:5863-71