Computational tools and Interoperability in Comparative ... - CBS

Conservation of regulatory elements
values.
nb,p
Rb,p = log2(4) + log2
N
L
Rtot = RB,p
p=1
(3.1)
–where b ∈ AT GC iterates through the four bases, p denotes the position in the
alignment, L is the length of the alignment (or width of the matrix), and nb,p is the
number of bases b at position p, and B denotes the nucleotide at position p in the query
sequence. Shultzaberger and co-workers account for the helical facing by introducing the
accessibility, n(d) (equation 3.2) and the gap surprisal, GS(d) (see equation 3.3).
n(d) = 1 + cos[ 2π
(d − c)] (3.2)
w
–where c is the center distance between two binding sites (e.g. optimally spaced), d is
the query distance, w = 10.6 is the distance of a one helix turn of B-form DNA. Finally,
this gives GS(d) as follows:
n(d)
GS(d) = log2
N
(3.3)
–where N is the sum of all n(d) (see equation 3.4). The sign of the GS(d) was changed
from the original equation described by Shultzaberger and co-workers to allow for combining
all scores by addition.
N =
max
d=min
n(d) (3.4)
–where min and max are the boundaries of a given window examined. Finally, summarizing
all Ri and GS(d) values gives the total information of all motifs and all spacers (see
figure 3.5)
Ri(tot) = Ri(m1) + GS(d, m1) + Ri(m2) + ... + GS(d, mn−1) + Ri(mn) (3.5)
3.3.1 Modeling the P1 and P2 in selected enterics
Existing experimentally verified –10 and –35 hexamers (Huerta & Collado-Vides, 2003)
were converted into Rb,p matrices together with data for known UP elements (Estrem
et al., 1998) and FIS binding sites (Hengen et al., 1997). Figure 3.4 shows logo plots of
the information content of these studies. The initial weight matrices founded the basis
for iteratively building the final information model of the P1 and P2 promotor structure,
using the following procedure:
1. E. coli and Shigella genomes
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2. rRNA gene finding and make upstream sequence
3. Apply models based on literature weight matrices
4. Refine weight matrices according to observations
5. Formulate final model