Sequence Comparison.pdf

Chapter 6
Anatomy of Spaced Seeds
BLAST was developed by Lipman and his collaborators to meet demanding needs
of homology search in the late 1980s. It is based on the filtration technique and
is multiple times faster than the Smith-Waterman algorithm. It first identifies short
exact matches (called seed matches) of a fixed length (usually 11 bases) and then
extends each match to both sides until a drop-off score is reached. Motivated by the
success of BLAST, several other seeding strategies were proposed at about the same
time in the early 2000s. In particular, PatternHunter demonstrates that an optimized
spaced seed improves sensitivity substantially. Accordingly, elucidating the mechanism
that confers power to spaced seeds and identifying good spaced seeds are two
new issues of homology search.
This chapter is divided into six sections. In Section 6.1, we define spaced seeds
and discuss the trade-off between sensitivity and specificity for homology search.
The sensitivity and specificity of a seeding-based program are largely related to
the probability that a seed match is expected to occur by chance, called the hit probability.
Here we study analytically spaced seeds in the Bernoulli sequence model
defined in Section 1.6. Section 6.2 gives a recurrence relation system for calculating
hit probability.
In Section 6.3, we investigate the expected distance µ between adjacent nonoverlapping
seed matches. By estimating µ, we further discuss why spaced seeds
are often more sensitive than the consecutive seed used in BLAST.
A spaced seed has a larger span than the consecutive seed of the same weight.
As a result, it has less hit probability in a small region but surpass the consecutive
seed for large regions. Section 6.4 studies the hit probability of spaced seeds
in asymptotic limit. Section 6.5 describes different methods for identifying good
spaced seeds.
Section 6.6 introduces briefly three generalizations of spaced seeds: transition
seeds, multiple spaced seeds, and vector seeds.
Finally, we conclude the chapter with the bibliographic notes in Section 6.7.
91