# Smith-Waterman algorithm

The Smith-Waterman algorithm is a well-known algorithm for performing local sequence alignment; that is, for determining similar regions between two nucleotide or protein sequences. Instead of looking at the total sequence, the Smith-Waterman algorithm compares segments of all possible lengths and optimizes the similarity measure.

## Background

The algorithm was first proposed by Temple Smith and Michael Waterman in 1981.[1] Like the Needleman-Wunsch algorithm, on which it is a variation, Smith-Waterman is a dynamic programming algorithm. As such, it has the desirable property that it is guaranteed to find the optimal local alignment with respect to the scoring system being used (which includes the substitution matrix and the gap-scoring scheme). The main difference to the Needleman-Wunsch algorithm is that negative scoring matrix cells are set to zero, which renders the (thus positively scoring) local alignments visible. Backtracing starts at the highest scoring matrix cell and proceeds until a cell with score zero is encountered, yielding the highest scoring local alignment.

One motivation for local alignment is the difficulty to obtain correct alignments in regions of low similarity between distantly related biological sequences, because mutations have added too much 'noise' in evolutionary times to allow for a meaningful comparison of these regions. Local alignment avoids these regions altogether and focuses on those with a positive score, i.e. those with an evolutionary conserved signal of similarity. A prerequisite for local alignment is a negative expectation score. The expectation score is defined as the average score that the scoring system (substitution matrix and gap penalties) would yield for a random sequence.

Another motivation for using local alignments is that there is a reliable statistical model (developed by Karlin and Altschul) for optimal local alignments. The alignment of unrelated sequences tends to produce optimal local alignment scores which follow an extreme value distribution. This property allows programs to produce an expectation value for the optimal local alignment of two sequences, which is a measure of how often two unrelated sequences would produce an optimal local alignment whose score is greater than or equal to the observed score. Very low expectation values indicate that the two sequences in question might be homologous, meaning they might share a common ancestor.

However, the Smith-Waterman algorithm is fairly demanding of time and memory resources: in order to align two sequences of lengths m and n, O(mn) time and space are required. As a result, it has largely been replaced in practical use by the BLAST algorithm; although not guaranteed to find optimal alignments, BLAST is much more efficient.

An implementation of the Smith-Waterman Algorithm, SSEARCH, is available in the FASTA sequence analysis package from ftp://ftp.virginia.edu/pub/fasta. This implementation includes Altivec accelerated code for PowerPC G4 and G5 processors that speeds up comparisons 10 - 20-fold, using a modification of the Wozniak, 1997 approach[2], making optimal protein database searches quite practical.

## Accelerated versions

### FPGA

Template:Primarysources Other recent work developed by Cray demonstrates acceleration of the Smith-Waterman algorithm using a reconfigurable computing platform based on FPGA chips.[3] The results show up to 28x speed-up over standard microprocessor-based solutions. A FPGA based version of the Smith-Waterman algorithm offered by Progeniq show up to 40x acceleration versus standard software implementation on the same processor.[4]

### GPU

Recent work developed at Lawrence Livermore National Laboratory and the US Department of Energy's Joint Genome Institute accelerates Smith-Waterman local sequence alignment searches using graphics processing units (GPUs) with preliminary results showing a 2x speed-up over software implementations. A similar method is already implemented into the Biofacet software since 1997, with the same speed-up factor [1].

### SSE

A SSE2 vectorization of the algorithm (Farrar, 2007) is now available providing an 8-fold speedup on Intel/AMD processors with SSE2 extensions.[5] When running on Intel processor using the new Intel Core microarchitecture the SSE2 implementation achieves a 20-fold increase.

Danish bioinformatics company CLC bio has achieved speed-ups of close to 200 over standard software implementations with SSE2 on a Intel 2.17 Ghz Core 2 Duo CPU, according to a publicly available white paper.

Accelerated version of the Smith-Waterman algorithm, on Intel and AMD based Linux servers, is supported by the GenCore 6 package, offered by Biocceleration. Performance benchmarks of this software package show up to 10 fold speed acceleration relative to standard software implementation on the same processor.

Currently the only company in bioinformatics to offer both SSE and FPGA solutions accelerating Smith-Waterman, CLC bio has achieved speed-ups of more than 110 over standard software implementations with CLC Bioinformatics Cube.

The TimeLogic DeCypher and CodeQuest systems also accelerate Smith-Waterman and Framesearch using FPGA technology.

## References

1. Smith TF, Waterman MS (1981). "Identification of Common Molecular Subsequences". Journal of Molecular Biology. 147: 195–197. External link in `|title=` (help)
2. Wozniak A (1997). "Using video-oriented instructions to speed up sequence comparison". Comput Appl Biosci. 13 (2): 145–50.
3. Cray Computer Corp, "Smith-Waterman Solution for Life Sciences".
4. Farrar M (2007). "Striped Smith–Waterman speeds database searches six times over other SIMD implementations". Bioinformatics. 23: 156–161.