Category: Objective Questions

Bioinformatics MCQs focuses on “Iterative Methods of Multiple Sequence Alignment”.

1. Iterative methods include repeatedly realigning subgroups of the sequences and then by aligning these subgroups into a local alignment of all of the sequences.
A. True
B. False

Answer: B
Explanation: Subgroups are aligned into a global alignment of all of the sequences. The objective is to improve the overall alignment score, such as a sum of pairs score. Selection of these groups may be based on the ordering of the sequences on a phylogenetic tree predicted in a manner similar to that of progressive alignment, separation of one or two of the sequences from the rest, or a random selection of the groups.

2. Which of the following is incorrect regarding PRRP?
A. The program PRRP uses iterative methods to produce an alignment
B. An initial pair-wise alignment is made to predict a tree
C. Only one cycle is performed
D. The whole process is repeated until there is no further increase in the alignment score

Answer: c
Explanation: As mentioned, an initial pair-wise alignment is made to predict a tree, the tree is used to produce weights for making alignments in the same manner as MSA except that the sequences are analyzed for the presence of aligned regions that include gaps rather than being globally aligned, and these regions are iteratively recalculated to improve the alignment score. The best scoring alignment is then used in a new cycle of calculations to predict a new tree, new weights, and new alignments.

3. In the program DIALIGN, pairs of sequences are aligned to locate aligned regions that do not include gaps, much like continuous diagonals in a dot matrix plot.
A. True
B. False

Answer: A
Explanation: The program DIALIGN finds an alignment by a different iterative method. Pairs of sequences are aligned to locate aligned regions that do not include gaps, much like continuous diagonals in a dot matrix plot. Diagonals of various lengths are identified. A consistent collection of weighted diagonals that provides an alignment which is a maximum sum of weights is then found.

4. The Genetic Algorithm method has been recently adapted for MSA(Multiple Sequence Alignment) by Corpet (1998).
A. True
B. False

Answer: B
Explanation: The genetic algorithm is a general type of machine-learning algorithm that has no direct relationship to biology and that was invented by computer scientists. The method has been recently adapted for MSA (Multiple Sequence Alignment) by Notredame and Higgins (1996) in a computer program package called SAGA (Sequence Alignment by Genetic Algorithm).

5. An approach for obtaining a higher-scoring MSA (Multiple Sequence Alignment) by rearranging an existing alignment uses a probability approach called simulated annealing.
A. True
B. False

Answer: A
Explanation: The program MSASA (Multiple Sequence Alignment by Simulated Annealing) starts with a heuristic MSA (Multiple Sequence Alignment). Further, it changes the alignment by following an algorithm designed to identify changes that increase the alignment score.

6. The first step in Genetic Algorithm is arranging the sequences to be aligned in rows.
A. True
B. False

Answer: A
Explanation: The sequences to be aligned are written in rows, as on a page, except that they are made to overlap by a random amount of sequence, up to 50 residues long for sequences about 200 in length. The ends are then padded with gaps. A typical population of 100 of these MSAs is made, although other numbers may be set.

7. The second step in the Genetic Algorithm comprises of scoring of the 100 initial MSAs by the sum of pairs method.
A. True
B. False

Answer: A
Explanation: The 100 initial MSAs are scored by the sum of pairs method, except that both natural and quasi-natural gap-scoring schemes are used. Recall that the best SSP score for a MSA is the minimum one and the one that is closest to the sum of the pair-wise sequence alignment. Standard amino acid scoring matrices and gap opening and extension penalties are used.

8. In Genetic Algorithm, in the mutation process _______
A. sequence is changed
B. gaps are not inserted
C. sequence is not changed
D. gaps are not rearranged

Answer: c
Explanation: In the mutation process, the sequence is not changed (else it would no longer be an alignment), but gaps are inserted and rearranged in an attempt to create a better-scoring MSA. In the gap insertion process, the sequences in a given MSA are divided into two groups based on an estimated phylogenetic tree, and gaps of random length are inserted into random positions in the alignment.

9. The HMM is a statistical model that considers few combinations of matches and gaps to generate an alignment of a set of sequences.
A. True
B. False

Answer: B
Explanation: The HMM is a statistical model that considers all possible combinations of matches, mismatches, and gaps to generate an alignment of a set of sequences. A localized region of similarity, including insertions and deletions, may also be modeled by an HMM. Analysis of sequences by an HMM is discussed on page 185 along with other statistical methods.

10. Which of the following is not true about iterative methods?
A. Genetic Algorithm is method used for under this
B. Hidden Markov Models are used for Multiple Sequence Alignment
C. The objective is to improve the overall alignment score
D. MultAlin recalculates global scores

Answer: D
Explanation: MultAlin (Corpet 1988) recalculates pair-wise scores during the production of a progressive Alignment. In addition, it uses these scores to recalculate the tree, which is then used to refine the alignment in an effort to improve the score.

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Bioinformatics Multiple Choice Questions on “Protein Structure Comparison”.

1. Which of the following is incorrect about protein structure comparison?
A. The comparative approach is important in finding remote protein homologs
B. Protein structures have a much higher degree of conservation than the sequences
C. Protein structures have a much lesser degree of conservation than the sequences
D. Proteins can share common structures even without sequence similarity

Answer: c
Explanation: Structure comparison is one of the fundamental techniques in protein structure analysis. Structure comparison can often reveal distant evolutionary relationships between proteins, which is not feasible using the sequence-based alignment approach alone. In addition, protein structure comparison is a prerequisite for protein structural classification into different fold classes.

2. The intermolecular approach is normally applied to relatively _____ structures.
A. distinctive
B. dissimilar
C. similar
D. different

Answer: c
Explanation: The algorithmic approaches to comparing protein geometric properties can be divided into three categories: the first superposes protein structures by minimizing intermolecular distances; the second relies on measuring intramolecular distances of a structure; and the third includes algorithms that combine both intermolecular and intramolecular approaches.

3. Which of the following is incorrect about intermolecular approach?
A. This procedure starts with identifying equivalent residues or atoms
B. After residue–residue correspondence is established, one of the structures is moved laterally and vertically toward the other structure to allow the two structures to be in the same location
C. The structures are rotated relative to each other around the three-dimensional axes
D. The rotation doesn’t depend on the intermolecular distance

Answer: D
Explanation: The rotation continues until the shortest intermolecular distance is reached. At this point, an optimal superimposition of the two structures is reached. After superimposition, equivalent residue pairs can be identified, which helps to quantitate the fitting between the two structures.

4. The root mean square deviation (RMSD), without the size dependency correction is?
A. (sum_{i=1}^N frac{D_i^2}{N})
B. (sum_{i=1}^N frac{D_i^2}{N + 1})
C. (sum_{i=1}^N frac{D_i^2}{N x N})
D. (sum_{i=1}^N frac{D_i^2}{N – 1})

Answer: A
Explanation: An important measurement of the structure fit during superposition is the distance between equivalent positions on the protein structures. This requires using a least square-fitting function called root mean square deviation (RMSD), which is the square root of the averaged sum of the squared differences of the atomic distances. Here D is the distance between coordinate data points and N is the total number of corresponding residue pairs.

5. The root mean square deviation (RMSD), with the size dependency correction is?
A. (frac{RMSD}{-1.3 + 0.5 ln⁡(N+1)})
B. (frac{RMSD}{-1.3 + 0.5 ln⁡(N x N)})
C. (frac{RMSD}{-1.3 + 0.5 ln⁡(N-1)})
D. (frac{RMSD}{-1.3 + 0.5 ln⁡(N)})

Answer: D
Explanation: In practice, only the distances between Cα carbons of corresponding residues are measured. The goal of structural comparison is to achieve a minimum RMSD. However, the problem with RMSD is that it depends on the size of the proteins being compared. For the same degree of sequence identity, large proteins tend to have higher RMSD values than small proteins when an optimal alignment is reached. Recently, a logarithmic factor has been proposed to correct this size-dependency problem. This new measure is called RMSD100.

6. The intramolecular approach does not depend on sequence similarity between the proteins to be compared.
A. True
B. False

Answer: A
Explanation: The intramolecular approach relies on structural internal statistics and therefore does not depend on sequence similarity between the proteins to be compared. In addition, this method does not generate a physical superposition of structures but instead provides a quantitative evaluation of the structural similarity between corresponding residue pairs.

7. Which of the following is incorrect about the intramolecular approach?
A. The method works by generating a distance matrix between residues of the same protein
B. It generates a string between residues of the same protein
C. In comparing two protein structures, the distance matrices from the two structures are moved relative to each other to achieve maximum overlaps
D. By overlaying two distance matrices, similar intramolecular distance patterns representing similar structure folding regions can be identified

Answer: B
Explanation: For the ease of comparison, each matrix is decomposed into smaller submatrices consisting of hexapeptide fragments. To maximize the similarity regions between two structures, a Monte Carlo procedure is used. By reducing three-dimensional information into two-dimensional information, this strategy identifies overall structural resemblances and common structure cores.

8. Which of the following is incorrect about Multiple Structure Alignment?
A. The alignment strategy is different than the Clustal sequence alignment using a progressive approach
B. All structures are first compared in a pairwise fashion
C. A distance matrix is developed based on structure similarity scores such as RMSD
D. The aligned structures create a median structure that allows other structures to be progressively added for comparison based on the hierarchy described in the guide tree

Answer: A
Explanation: In addition to pairwise alignment, a number of algorithms can also perform multiple structure alignment. The alignment strategy is similar to the Clustal sequence alignment using a progressive approach. When all the structures in the set are added, this eventually creates a multiple structure alignment.

9. Which of the following is incorrect about SSAP?
A. It is a web server that uses an intramolecular distance–based method
B. Matrices are built based on the Cβ distances of all residue pairs
C. Dynamic programming approach is not used here
D. Dynamic programming approach is used

Answer: c
Explanation: When comparing two different matrices, a dynamic programming approach is used to find the path of residue positions with optimal scores. The dynamic programming is applied at two levels, one at a lower level in which all residue pairs between the proteins are compared and another at an upper level in which subsequently identified equivalent residue pairs are processed to refine the matching positions. An SSAP score is reported for structural similarity. A score above 70 indicates a good structural similarity.

10. VAST is a web server that performs alignment using intramolecular approaches only.
A. True
B. False

Answer: B
Explanation: VAST (Vector Alignment Search Tool) is a web server that performs alignment using both the inter- and intramolecular approaches. The superposition is based on information of directionality of secondary structural elements (represented as vectors). Optimal alignment between two structures is defined by the highest degree of vector matches.

Genetic Engineering Multiple Choice Questions on “Reporter Genes”.

1. Promoter-probe vectors are used often. Choose the correct statement for these vectors.
a) They are used for identifying sequences that can function as promoter in vivo
b) It contains a reporter gene which contains its promoter along
c) The reporter gene is having a cloning site
d) After insertion of DNA into the cloning site, selection of plasmids is carried out by blue white screening
Answer: a
Explanation: Promoter- probe vectors are used for identification of sequences that can function as a promoter in vivo. It consists of a reporter gene which is not having its promoter along but other genes such as those for chloramphenicol resistance are present. The reporter gene is preceded by the cloning site and after the insertion of DNA has been done, selection of plasmids is carried out by using chloramphenicol resistance.

2. GFP is one of a marker which is used for screening libraries in hosts other than E. coli. Choose the incorrect statement for GFP.
a) It stands for Green Fluorescent Protein
b) It is obtained from a bio-luminescent jellyfish and produces protein aequorin which emits blue light
c) The blue light is produced because of binding of sodium ions
d) The absorbed blue light produces green light which can be detected further
Answer: c
Explanation: It stands for green fluorescent protein and is obtained from a bio-luminescent jellyfish. The jellyfish produces protein aequorin which produces blue light. This blue light is produced because of binding Calcium ions. The absorbed blue light emits green light which is detected further.

3. Luciferase genes are also used at times for detection. Choose the correct statement for them.
a) They are obtained from fire flies only
b) The detection requires provision of substrate which produces light
c) Enzymes such as beta-galactosidase requires substrate X-gluc to produce light
d) Lucifearse genes are preferred over fluorescent proteins
Answer: b
Explanation: Luciferase genes are not obtained only from fire flies but also from bio-luminescent bacteria and a sea pansy. The section requires a substrate which produces light. Enzymes such as beta-galactosidase requires X-gal for the production of blue light. Fluorescent proteins are more preferable over these because they don’t require substrates like luciferase genes.

4. In case of promoter-probe vectors, the same or related species should be as a vector whose DNA is to be screened.
a) True
b) False
Answer: a
Explanation: For promoter-probe vectors, the same species should be used as a host for the vector whose DNA is to be screened. It is so because a gene which is a promoter in one species may not be a promoter in other gene and thus it becomes difficult to detect.

5. Sequences that can function as origins of replication are called as ___________
a) partial replicating sequences
b) self replicating sequences
c) autonomously replicating sequences
d) modified replicating sequences
Answer: c
Explanation: There are some sequences which can function as origins of replication and they are known as autonomously replicating sequences (ARS). At times, the selection is carried out for these sequences.

6. Screening is often carried out for a sequence that interacts with a protein for which already a clone is present. It is carried out in which host?
a) Bacterial host
b) Fungal host
c) Parasitic host
d) Yeast host
Answer: d
Explanation: Screening is often carried out for a sequence that interacts with a protein for which already a clone is present. This type of screening is often carried out in a yeast host.

7. In two hybrid screening system, the activator binds through _______ domain to a sequence upstream of the gene under its control, and ________ domain stimulates transcription.
a) DNA binding, activation
b) Activation, DNA binding
c) Activation, transcription
d) DNA binding, transcription
Answer: a
Explanation: The two hybrid-screening system is based on the fact that many transcriptional activators consist of two domains, the DNA binding domain and activation domain. The activator binds through the DNA binding domain to a sequence upstream of the gene under its control. The activation domain stimulates transcription.

8. For two hybrid systems, activation domains can be present in different proteins also rather than being on a single protein. A sequence encodes _______ protein for which we want to find an interacting protein.
a) prey
b) bait
c) binding
d) activation
Answer: b
Explanation: Bait protein is the name given to the protein for whom we are looking for an interacting protein. Bait protein is cloned adjacent to the DNA binding protein. The protein interacting with bait protein is called as prey protein and leading to activation of domains.

9. The transcription domain is ________ if some of the bait and prey proteins are non-specific in nature?
a) deactivated
b) activated
c) destroyed
d) may be activated or not
Answer: d
Explanation: If the bait and prey proteins are non-specific in nature, some of them might lead to activation of the transcription domain without the presence of another domain.

10. _____ should enter the cell in the case of activation of the reporter gene for two hybrid system.
a) Bait protein
b) Prey protein
c) Both bait and prey protein
d) Either one of them
Answer: c
Explanation: Both prey and bait proteins should enter inside the cell for activation of the reporter gene for two hybrid system. It is so because activation is based on the interaction of these two proteins.

11. Protein-protein interactions such as in electron transport lead to activation of the reporter gene.
a) True
b) False
Answer: b
Explanation: Protein-protein interactions are weak interactions and thus they are not sufficient for the activation of the reporter gene.