Biology Reference
In-Depth Information
Fig. 1 Schematic overview of the profile preprocessing (a) and the pre-profile alignment (b) routines.
For details, see text. Adapted from ref.
8
be recognized by global alignment, PRALINE offers a number of
strategies to address evolutionary divergent alignment situations.
Pre-profile processing is an optimization method aimed at mini-
mizing error propagation during progressive alignment by includ-
ing prior knowledge about the other sequences during alignment
[
7
]. In this method each of the input sequences is represented as a
preprocessed profile (pre-profile) instead of a single sequence. For
each input sequence a master-slave alignment is constructed by
stacking other input sequences whose pairwise global alignment
score against the master sequence is higher than a user-specified
threshold (Fig.
1
). The user can determine whether to include
distant sequences in the pre-profile or not to use an alignment
score threshold value. Although distant sequences might contrib-
ute significant information, there is the chance that they contribute
noise due to the fact that alignment error is known to increase
super-linearly with sequence distance [
14
].
PRALINE allows the alignment score threshold value to be
specified as a factor relating to the sequence lengths:
S
2.2 Global
Pre-profile
Preprocessing
tL
, where
L
is the length of the shortest sequence in the alignment and
t
is the
alignment score threshold. This means that the alignment score
S
should be at least as high as the threshold score multiplied by
L
in
order to become included in the pre-profile such that the average
score over
L
positions is at least
t
. Using a score threshold which is
linearly related to alignment length is in agreement with observa-
tions made for global alignments of random sequences [
8
,
15
].
The pre-profiles in PRALINE further incorporate position-
specific gap penalties, enabling increased matching of distant
sequences and likely placement of gaps outside ungapped core
regions in the pre-profiles during progressive alignment.