Revisiting the Speed-versus-Sensitivity Tradeoff in Pairwise Sequence Search

The Smith-Waterman algorithm is a dynamic programming method for determining optimal local alignments between nucleotide or protein sequences. However, it suffers from quadratic time and space complexity. As a result, many algorithmic and architectural enhancements have been proposed to solve this problem, but at the cost of reduced sensitivity in the algorithms or significant expense in hardware, respectively. Hence, there exists a need to evaluate the tradeoffs between the different solutions. This motivation, coupled with the lack of an evaluation metric to quantify these tradeoffs leads us to formally define and quantify the sensitivity of homology search methods so that tradeoffs between sequence-search solutions can be evaluated in a quantitative manner. As an example, though the BLAST algorithm executes significantly faster than Smith-Waterman, we find that BLAST misses 80% of the significant sequence alignments. This paper then presents a highly efficient parallelization of the Smith-Waterman algorithm on the Cell Broadband Engine, a novel hybrid multicore architecture that drives the PlayStation 3 (PS3) game consoles, and emulates BLAST by repeatedly executing the parallelized Smith-Waterman algorithm to search for a query in a given sequence database. Through an innovative mapping of the optimal Smith-Waterman algorithm onto a cluster of PlayStation 3 nodes, our implementation delivers a 10-fold speed-up over a high-end multicore architecture and an 88-fold speed-up over a non-accelerated PS3. Finally, we compare the performance of our implementation of the Smith-Waterman algorithm to that of BLAST and the canonical Smith-Waterman implementation, based on a combination of three factors — execution time (speed), sensitivity, and the actual cost of deploying each solution. In the end, our parallelized Smith-Waterman algorithm approaches the speed of BLAST while maintaining ideal sensitivity and achieving low cost through the use of PlayStation 3 game consoles.