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Scoring Matrices
Shifra Ben-Dor
Irit Orr

Scoring matrices
❆ Sequence alignment and database searching

programs compare sequences to each other
as a series of characters
...

❆ Scoring matrices are used to assign a score
to each comparison of a pair of characters
...

❆ In most cases a positive score is given to

identical or similar character pairs, and a
negative or zero score to dissimilar
character pairs
...
This scoring scheme is not much used
...
This matrix
scores identical bp 3, transitions 2, and
transversions 0
...
g
size, shape or charge of the aa)
...
These
matrices are constructed by analyzing the
substitution frequencies seen in the
alignments of known families of proteins
...

• This score is based on the observed
frequencies of such occurrences in
alignments of evolutionary related proteins
...


Observed Scoring Matrices
• Identities are assigned the most positive

scores
• Frequently observed substitutions also
receive positive scores
• Mismatches , or matches that are unlikely
to have been a result of evolution, are
given negative scores
...

• These ratios are called odds scores
...

• Odds scores and log odds scores are used to
score protein alignments

Different types of matrices
• Observed Scoring Matrices are superior to

simple identity scores, or scores based
solely on chemical propensities of the
amino

• The most frequently used observed log odds

matrices used are the PAM and BLOSUM
matrices
...

❆ Derived from global alignments of very
similar sequences (at least 85% identity), so
that there would be little likelihood of an
observed change being the result of several
successive mutations, but it should reflect
one mutation only
...


❆ An accepted point mutation in a protein is a

replacement of one amino acid by another,
accepted by natural selection
...
To be
accepted, the new amino acid usually must
function in a way similar to the old one: chemical
and physical similarities are found between the
amino acids that are observed to interchange
frequently
...

❆ PAM gives the probability that a given
amino acid will be replaced by any other
particular amino acid after a given
evolutionary interval, in this case 1 accepted
point mutation per 100 amino acids
...
(this
lets us add the scores along a protein instead
of multiplying the probabilities)
❆ The resulting matrix is the “log-odds”
matrix, known as the PAM matrix
...
Greater numbers are greater
distances
...


PAM250
❆ At this evolutionary distance, only one amino acid in

five remains unchanged
...
52% of the
cysteines and 27% of the glycines would still be
unchanged, but only 6% of the highly mutable
asparagines would remain
...
0
...
231049
Expected score = -0
...
354 bits
Lowest score = -8, Highest score = 17
A
2
-2
0
0
-2
0
0
1
-1
-1
-2
-1
-1
-3
1
1
1

R
-2
6
0
-1
-4
1
-1
-3
2
-2
-3
3
0
-4
0
0
-1

N
0
0
2
2
-4
1
1
0
2
-2
-3
1
-2
-3
0
1
0

D
0
-1
2
4
-5
2
3
1
1
-2
-4
0
-3
-6
-1
0
0

C
-2
-4
-4
-5
12
-5
-5
-3
-3
-2
-6
-5
-5
-4
-3
0
-2

Q
0
1
1
2
-5
4
2
-1
3
-2
-2
1
-1
-5
0
-1
-1

E
0
-1
1
3
-5
2
4
0
1
-2
-3
0
-2
-5
-1
0
0

G
1
-3
0
1
-3
-1
0
5
-2
-3
-4
-2
-3
-5
0
1
0

H
-1
2
2
1
-3
3
1
-2
6
-2
-2
0
-2
-2
0
-1
-1

I
-1
-2
-2
-2
-2
-2
-2
-3
-2
5
2
-2
2
1
-2
-1
0

L
-2
-3
-3
-4
-6
-2
-3
-4
-2
2
6
-3
4
2
-3
-3
-2

K
-1
3
1
0
-5
1
0
-2
0
-2
-3
5
0
-5
-1
0
0

M
-1
0
-2
-3
-5
-1
-2
-3
-2
2
4
0
6
0
-2
-2
-1

F
-3
-4
-3
-6
-4
-5
-5
-5
-2
1
2
-5
0
9
-5
-3
-3

P
1
0
0
-1
-3
0
-1
0
0
-2
-3
-1
-2
-5
6
1
0

S
1
0
1
0
0
-1
0
1
-1
-1
-3
0
-2
-3
1
2
1

T
1
-1
0
0
-2
-1
0
0
-1
0
-2
0
-1
-3
0
1
3

W
-6
2
-4
-7
-8
-5
-7
-7
-3
-5
-2
-3
-4
0
-6
-2
-5

Y
-3
-4
-2
-4
0
-4
-4
-5
0
-1
-1
-4
-2
7
-5
-3
-3

V
0
-2
-2
-2
-2
-2
-2
-1
-2
4
2
-2
2
-1
-1
-1
0

B
0
-1
2
3
-4
1
3
0
1
-2
-3
1
-2
-4
-1
0
0

Z
0
0
1
3
-5
3
3
0
2
-2
-3
0
-2
-5
0
0
-1

X
0
-1
0
-1
-3
-1
-1
-1
-1
-1
-1
-1
-1
-2
-1
0
0

*
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8
-8

Pet91 - an updated Dayhoff matrix
❆ Since the family of PAM matrices were

derived from a comparatively small number
of families, many of the possible mutations
were not observed
...
have derived an updated matrix
by examining a very large number of
families, and created the PET91 scoring
matrix
...

❆ First, multiple alignments of short regions
(without gaps) of related sequences were
gathered
...


BLOSUM Matrices
❆ Substitution frequencies for all pairs of

amino acids were calculated between the
groups, this was used to create the log-odds
BLOSUM ( Block Substitution Matrix )
...

❆ Thus, BLOSUM62 means that the

sequences clustered in this block are at
least 62% identical
...


BLOSUM62 MATRIX
#
#
#
#
#
#
A
R
N
D
C
Q
E
G
H
I
L
K
M
F
P
S
T
W
Y

Matrix made by matblas from blosum62
...
0/blocks
...
6979, Expected = -0
...

❆ Lower PAM matrices tend to find short
alignments of highly similar regions
...

❆ For local alignments use BLOSUM matrices
...

❆ BLOSUM matrices with LOW number, are
better for distant sequences
...

❆ When doing global alignment (and database

scanning) of related (similar) sequences use
PAM200 or PAM250
...
g
...

❆ For local database scanning (e
...


Tips…
...




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