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Practical Innovation at BioCon 2003

Poster Session

Hardware accelerated iterative sequence profile search

By Roland Luethy
Ph.D., TimeLogic Corp.

Iterative sequence database searches have been shown to increase sensitivity for detection of distant similarity between protein sequences. The most popular tool for iterative searches is currently PSI-BLAST. Methods using dynamic programming alignment techniques have been generally considered to be too time consuming for iterative searches. TimeLogicıs DeCypher system accelerates such dynamic programming algorithms and makes it feasible to test iterative profile searches. We have implemented an iterative search method using position specific scoring matrices (PSSM) that were created in a similar fashion to the ones used in PSI-BLAST. These PSSMs were used with TimeLogicıs profilesearch implementation on the DeCypher accelerated bioinformatics system. To test the method, the sequences of the ASTRAL SCOP database with less than 40% identity were used to make PSSMs and the resulting profiles were then used to search the same database. Receiver operating characteristics curves were generated to compare the results using the dynamic algorithm based method and PSI-BLAST. Matches were considered correct positives if the superfamily assignment of the query and the match from SCOP were identical. The new method demonstrates an increased sensitivity at low error rates and -- with fixed error rate of 1% -- it finds 11% more true positives than PSI-BLAST.

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