This set of Bioinformatics Questions and Answers for Experienced people focuses on “Use of Scoring Matrices and Gap Penalties in Sequence Alignments”.
1. In scoring matrices, for convenience, odds scores are converted to log odds scores.
a) True
b) False
View Answer
Explanation: The odds scores are converted to log odds scores so that the values for amino acid pairs in an alignment may be summed to obtain the log odds score of the alignment. In this case, the logarithms are calculated to the base 2 and multiplied by 2 to give values designated as half-bits (a bit is the unit of an odds score that has been converted to a logarithm to the base 2). The value of 4 indicates that the 4 amino acid alignment is 2(4/2) = 4 four-fold more likely than expected by chance.
2. Which of the following doesn’t describe PAM matrices?
a) This family of matrices lists the likelihood of change from one amino acid to another in homologous protein sequences during evolution
b) There is presently no other type of scoring matrix that is based on such sound evolutionary principles as are these matrices
c) Even though they were originally based on a relatively small data set, the PAM matrices remain a useful tool for sequence alignment
d) It stands for Percent Altered Mutation
View Answer
Explanation: PAM stands for Percent Accepted Mutation. In this, each matrix gives the changes expected for a given period of evolutionary time, evidenced by decreased sequence similarity as genes encoding the same protein diverge with increased evolutionary time.
3. The assumption in this evolutionary model is that the amino acid substitutions observed over short periods of evolutionary history can be extrapolated to longer distances.
a) True
b) False
View Answer
Explanation: The BLOSUM matrices are based on scoring substitutions found over a range of evolutionary periods and reveal that substitutions are not always as predicted by the PAM model. The purpose of assumption in this evolutionary model is to make predictions.
4. Which of the following is untrue about the modification of PAM matrices?
a) At one time, the PAM250 scoring matrix was modified in an attempt to improve the alignment obtained
b) All scores for matching a particular amino acid were normalized to the same mean and standard deviation, and all amino acid identities were given the same score to provide an equal contribution for each amino acid in a sequence alignment
c) This took place in 1976
d) These modifications were included as the default matrices for the GCG sequence alignment programs in versions 8 and earlier and are optional in later versions
View Answer
Explanation: This event took place in 1986 by Gribskov and Burgess. However, they are not recommended because they will not give an optimal alignment that is in accordance with the evolutionary model.
5. The Dayhoff model of protein evolution is not a Markov process.
a) True
b) False
View Answer
Explanation: The Dayhoff Model of Protein Evolution as Used in PAM Matrices is a Markov process. In Analysis of the Dayhoff Model, each amino acid site in a protein can change at any time to any of the other 20 amino acids with probabilities given by the PAM table, and the changes that occur at each site are independent of the amino acids found at other sites in the protein and depend only on the current amino acid at the site.
6. Which of the following is true regarding the assumptions in the method of constructing the Dayhoff scoring matrix?
a) it is assumed that each amino acid position is equally mutable
b) it is assumed that each amino acid position is not equally mutable
c) it is assumed that each amino acid position is not mutable at all
d) sites do not vary in their degree of mutability
View Answer
Explanation: In this process, first, it is assumed that each amino acid position is equally mutable, whereas, in fact, sites vary considerably in their degree of mutability. Mutagenesis hot spots are well known in molecular genetics, and variations in mutability of different amino acid sites in proteins are well known.
7. The more conserved amino acids in similar proteins from different species are ones that play an essential role in structure and function and the less conserved are in sites that can vary without having a significant effect on function.
a) True
b) False
View Answer
Explanation: There are many factors that influence both the location and types of amino acid changes that occur in proteins. Wilbur (1985) has tested the Markov model of evolution and has shown that it can be valid if certain changes are made in the way that the PAM matrices are calculated.
8. A gap opening penalty for any gap (g) and a gap extension penalty for each element in the gap (r) are most often used, to give a total gap score wx, according to the equation ______
a) wx – rx = -g
b) wx = g – rx
c) wx = g + rx
d) wx + g + rx = 0
View Answer
Explanation: wx = g + rx is the equation where x is the length of the gap. in some formulations of the gap penalty, the equation wx = g + r (x – 1) is used. Thus, the gap extension penalty is not added to the gap opening penalty until the gap size is 2.
9. In the GCG and FASTA program suites, the scoring matrix itself is formatted in a way that includes default ______
a) gap additions
b) alignment scores
c) score penalties
d) gap penalties
View Answer
Explanation: These program suites include default gap penalties. When deciding gap penalties for local alignment programs, a consideration is that the penalties should be large enough to provide a local alignment of the sequences.
10. In case of the varying alignment, penalizing gaps heavily might occur. Then the best scoring local alignment between the sequences will be one that optimizes the score between matches and mismatches, without any gaps.
a) True
b) False
View Answer
Explanation: If both mismatches and gaps are heavily penalized, the resulting alignment will also be a local alignment that contains the longest region of exact matches. In the above two cases, the alignment score of the highest-scoring local alignment will increase as the logarithm of the length of the sequences. Under these same conditions, the score of the corresponding global alignment between the sequences will be negative.
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