Nucleotide Substitution Matrix With Iupac Nucleotide Ambiguity Codes

Question

[tommivat]

I'm looking for a substitution matrix for aligning short DNA sequences using IUPAC nucleotide ambiguity codes. I would guess there are existing solutions but I haven't found any despite of extensive googling.

Answer 1

[Pierre Lindenbaum]

ftp://ftp.ncbi.nih.gov/blast/matrices/NUC.4.4

#
# This matrix was created by Todd Lowe   12/10/92
#
# Uses ambiguous nucleotide codes, probabilities rounded to
#  nearest integer
#
# Lowest score = -4, Highest score = 5
#
    A   T   G   C   S   W   R   Y   K   M   B   V   H   D   N
A   5  -4  -4  -4  -4   1   1  -4  -4   1  -4  -1  -1  -1  -2
T  -4   5  -4  -4  -4   1  -4   1   1  -4  -1  -4  -1  -1  -2
G  -4  -4   5  -4   1  -4   1  -4   1  -4  -1  -1  -4  -1  -2
C  -4  -4  -4   5   1  -4  -4   1  -4   1  -1  -1  -1  -4  -2
S  -4  -4   1   1  -1  -4  -2  -2  -2  -2  -1  -1  -3  -3  -1
W   1   1  -4  -4  -4  -1  -2  -2  -2  -2  -3  -3  -1  -1  -1
R   1  -4   1  -4  -2  -2  -1  -4  -2  -2  -3  -1  -3  -1  -1
Y  -4   1  -4   1  -2  -2  -4  -1  -2  -2  -1  -3  -1  -3  -1
K  -4   1   1  -4  -2  -2  -2  -2  -1  -4  -1  -3  -3  -1  -1
M   1  -4  -4   1  -2  -2  -2  -2  -4  -1  -3  -1  -1  -3  -1
B  -4  -1  -1  -1  -1  -3  -3  -1  -1  -3  -1  -2  -2  -2  -1
V  -1  -4  -1  -1  -1  -3  -1  -3  -3  -1  -2  -1  -2  -2  -1
H  -1  -1  -4  -1  -3  -1  -3  -1  -3  -1  -2  -2  -1  -2  -1  
D  -1  -1  -1  -4  -3  -1  -1  -3  -1  -3  -2  -2  -2  -1  -1
N  -2  -2  -2  -2  -1  -1  -1  -1  -1  -1  -1  -1  -1  -1  -1

[lh3]

Just beware that this matrix derived from the fasta aligner. It is for distant homology searches. For intra-species alignment, the mismatch penalty is higher than a matching score.

[hcraigwriter]

Is it possible to change the penalties to reflect matches among the IUPACs? If so how?
It penalizes B (C,G,T) , D(A,G,T), H(A,C,T), V(A,C,G) negatively (negative score with all other NTs and ambiguous codes & self) and will be represented as mismatch in the alignment with their respective NTs & itself. For e.g. B will be a mismatch with B and B will be a mismatch with C/G/T.

[tommivat]

Thanks for the spot on answer! My task is aligning human normal - tumor fragments. What kind of penalty would you suggest for opening end extending a gap?

[tflutre]

I just found this answer on EMBOSS mailing list: "NUC4.2 (EDNAMAT) simply scores 5 for a match, and -4 for a mismatch. NUC4.4 (EDNAFULL) scores 5 for a match, but provides appropriate scores for ambiguity codes so that, for example, R:A scores +1 (rounded up average of -4, -4, 5, 5)". These two matrices are handled by the program "water" from EMBOSS, also available online. About defining gap penalties, this book should help: Durbin, R., Eddy, S. R., Krogh, A. & Mitchison, G. Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids (Cambridge University Press, 1998). URL http://www.worldcat.org/isbn/0521629713.