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Correct choice is (a) True

To explain I would say: It is available from SEVERAL ANONYMOUS FTP SITES. This interface requires communication with a host UNIX machine running the Genetics Computer Group software. Interface with MS-DOS or Macintosh is possible if the computer is equipped with the appropriate X-Windows CLIENT software.

The CORRECT OPTION is (a) True

Explanation: For example, that there are four GS in the first column of the 10 sequences, then the frequency of G in the first column of the site, FSG = 4/10 = 0.4. This procedure is repeated for each base and each column.

Right choice is (a) the maximization step

To ELABORATE: In step 2, the maximization step, the new counts of bases or AMINO acids for each position in the site found in step 1 are SUBSTITUTED for the previous set. Step 1 is then repeated using these new counts. The cycle is repeated until the algorithm converges on a solution and does not change with further cycles. At that time, the best location of the site in each sequence and the best estimate of the residue composition of each column in the site will be available.

Right option is (b) False

The BEST explanation: In a multidimensional search matrix, for aligning N sequences, an N-dimensional matrix is needed to be filled with alignment scores. For instance, for three sequences, a three-dimensional matrix is REQUIRED to ACCOUNT for all possible alignment scores. Back-tracking is applied through the three-dimensional matrix to FIND the HIGHEST scored path that represents the optimal alignment.

The correct answer is (a) True

For explanation: In this method, the probability of each location is then FOUND by multiplying the odds scores from each column. An even SIMPLER method is to use log odds scores in the matrix. The column scores are then simply ADDED. In this case, the log odds scores must be CONVERTED to odds scores before position probabilities are calculated.

The CORRECT answer is (a) True

The best explanation: The very first sequences to be aligned are the most closely related on the sequence TREE. If these sequences align very well, there will be few errors in the initial alignments. HOWEVER, the more distantly related these sequences, the more errors will be made, and these errors will be propagated to the MSA. There is no simple way to circumvent this PROBLEM. A SECOND problem with the progressive alignment method is the choice of suitable scoring matrices and gap penalties that apply to the set of sequences.

Correct answer is (d) Blocks may be made by SEARCHING for a section of an MSA alignment that is low CONSERVED

The best explanation: LIKE profiles, blocks may be made by searching for a section of an MSA alignment that is highly conserved. HOWEVER, aligned regions may also be found by searching each sequence in turn for similar patterns of the same length. These patterns may include a region with one or a few matching characters followed by a short spacer region of unmatched characters and then by another set of a few matching characters, and so on, until the sequences START to be different.

Right choice is (a) True

BEST 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.

The CORRECT option is (b) Basic idea here is to build up the best alignment by USING optimal ALIGNMENTS of LARGER subsequences

The explanation: In case of Needleman-Wunsch algorithm, the basic idea here is to build up the best alignment by using optimal alignments of SMALLER subsequences. It is based on dynamic programming, a discipline invented by Richard Bellman in 1953.

The correct choice is (b) 10

The explanation is: When EXAMINING the EM program MEME, the size and number of binding sites, the LOCATION in each SEQUENCE, and whether or not the SITE is present in each sequence do not necessarily have to be known. For the present example, the following steps would be used by the EM ALGORITHM to find the most probable location of the binding sites in each of the 10 sequences.

The CORRECT answer is (C) Only one cycle is performed

To explain: 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.

The correct choice is (c) global, more highly CONSERVED

For explanation I would say: Profiles are found by performing the global MSA of a group of sequences and then removing the more highly conserved regions in the alignment into a smaller MSA. A scoring MATRIX for the MSA, CALLED a profile, is then made. The profile is composed of columns MUCH like a mini-MSA and may include matches, mismatches, insertions, and deletions.

Correct choice is (b) False

Easy 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).

Correct CHOICE is (b) False

Explanation: Knowing how many counts to add is a difficult but fortunately solvable problem. On the one hand, if too many pseudocounts are added in comparison to real sequence counts, the pseudocounts will become the DOMINANT influence in the amino acid frequencies and SEARCHES using the motif will not WORK. On the other hand, if there are relatively few real counts, many amino acid VARIATIONS may not be present because of the small sample of sequences.

Right option is (d) Faster, full dynamic programming method

The best explanation: The methods used, might be fast k-tuple or pattern-finding approach similar to FASTA that is useful for MANY sequences and the full dynamic programming method as well. But the option d becomes incorrect as full dynamic programming method is slower as COMPARED to rest of the methods in OPTIONS.

The correct answer is (a) True

Explanation: Probably the most well-known progressive alignment program is CLUSTAL. The stand-alone program, which RUNS on UNIX and MACINTOSH, has two variants, Clustal W and Clustal X. The W version PROVIDES a simple text-based interface and the X version provides a more user-friendly graphical interface.

Correct choice is (b) False

For explanation I would say: Given a multiple alignment of three sequences, the sum of scores is CALCULATED as the sum of the similarity scores of every pair of sequences at each position. The scoring is BASED on the BLOSUM62 matrix. If the total score for the alignment is 5, which MEANS that the alignment is 25 = 32 times more likely to OCCUR among homologous sequences than by random CHANCE.

The correct OPTION is (d) Its drawback is it SLOWS down the alignment of multiple SEQUENCES through a SINGLE step process

Explanation: Progressive alignment speeds up the alignment of multiple sequences through a multistep process further, the scores can either be percent identity or similarity scores based on a particular substitution matrix. Both scores correlate with the evolutionary distances between sequences.

Right ANSWER is (d) Number of gap penalties

The explanation is: In calculating the SP scores, each column is scored by summing the scores for all possible pair wise matches, mismatches and gap COSTS. The SCORE of the entire alignment is the sum of all of the column scores. The score of the entire alignment is the sum of all of the column scores. In that case, option d BECOMES irrelevant choice here.

Right choice is (a) True

Easiest explanation: USE of +1 as a reward for a match, -1 as the penalty for a mismatch, and IGNORING gaps is the scoring scheme of this type of method. Hence, the alignment score is the sum of substitution SCORES and gap penalties in this type of algorithm.

Right answer is (C) To study the PHYSICAL properties of molecules

To explain: To assess whether it is likely that two sequences evolved from the same sequence COMPARISON is required. ALSO, to FIND out which sequences from the database are similar to the sequence at hand, sequence comparison is carried out.

Right answer is (d) The PROGRAM MOTIF doesn’t locate spaced patterns

Easiest explanation: Blocks are found in two steps: FIRST, the program MOTIF described on the previous page is USED to locate spaced patterns. The SECOND step takes the best and most consistent patterns found in step 1 and uses the program MOTOMAT to merge overlapping triplets and extend them, orders the resulting blocks, and chooses those that are in the largest subset of sequences.

Correct answer is (d) MultAlin recalculates global scores

Easiest 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.

Correct option is (c) 81

Explanation: For the 10-residue DNA SEQUENCE EXAMPLE, there are 100 – 20 +1 possible starting sites for a 20-residue-long site. Where the first one is at POSITION 1 in the sequence ENDING one at 20 and the last beginning at position 81 and ending at 100 (there is not enough sequence for a 20-residue-long site beyond position 81).

Right choice is (a) True

Easiest EXPLANATION: The PROGRESSIVE alignment methods use the dynamic PROGRAMMING method. RELATIONSHIPS among the SEQUENCES are modeled by an evolutionary tree in which the outer branches or leaves are the sequences. The tree is based on pair-wise comparisons of the sequences using one of the phylogenetic methods.

Correct ANSWER is (b) False

For explanation: CLUSTAL uses a penalty for opening a gap in a sequence alignment and an additional penalty for extending the gap by one residue. These penalties are user-defined. Gaps found in the initial alignments remain fixed. New gaps INTRODUCED as more SEQUENCES are added also receive this same gap penalty, even when they occur within an existing gap, but the gap penalties for alignment are then modified according to the average match value in the SUBSTITUTION matrix, the percent identity between the sequences, and the sequence lengths.

The correct answer is (C) This scheme is useful in enhancing similar SEQUENCES from DOMINATING the alignment

To explain: This scheme is useful in enhancing similar sequences from dominating the alignment. Further, the weight factor for each sequence is DETERMINED by its branch length on the guide tree. The branch LENGTHS are normalized by how many times sequences share a basal branch from the root of the tree.

Right answer is (b) each column

Easiest explanation: The QUALITY and quantity of INFORMATION PROVIDED by the PSSM also varies for each column in the motif, and this variation profoundly influences the matches found with sequences. This situation can be accurately DESCRIBED by information theory, and the results can be displayed by a colored graph called a sequence logo.

Correct choice is (a) True

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.

Right option is (B) If a given column in 20 sequences has only isoleucine, it is very likely that DIFFERENT AMINO acid will be found in other sequences with that motif because the residue is probably IMPORTANT for function

Easy explanation: The PSSM is constructed by a simple logarithmic TRANSFORMATION of a matrix giving the frequency of each amino acid in the motif. Even more variation may be expected at that position in other sequences, although the more abundant amino acids already found in that column would probably be favored.

The correct choice is (d) The Web page has multiple versions for searching blocks by an EM algorithm

The best explanation: The Web page for two versions of MEME, ParaMEME, a Web program that SEARCHES for blocks by an EM algorithm (Described below), and a similar program MetaMEME (which searches for profiles USING HMMs, described below).The Motif Alignment and Search TOOL (MAST) for searching through databases for matches to MOTIFS.

Right OPTION is (b) False

The explanation: This ALGORITHM has been used to identify both conserved domains in unaligned proteins and protein-binding sites in unaligned DNA sequences (Lawrence and Reilly 1990), including sites that may include GAPS (CARDON and Stormo 1992). Given are a set of sequences that are expected to have a common sequence pattern and may not be easily recognizable by eye.

The correct option is (b) False

Explanation: These methods do not use substitution matrices such as the PAM and BLOSUM matrices to score matches. RATHER, they are based on finding exact matches that have the same SPACING in at least some of the input sequences, and that may be repeated in a GIVEN sequence.

Correct choice is (b) False

For explanation I would say: The GLOBAL sequence alignment is suitable when the two sequences are of SIMILAR length, with a SIGNIFICANT degree of similarity throughout. It GIVES the BEST alignment over the entire length of two sequences.

Right answer is (d) In the inner iteration, the sequences are randomly divided into multiple groups

To explain: In the inner iteration, the sequences are randomly divided into two groups. Randomized alignment is used for each group in the INITIAL cycle, after which the alignment positions in each group are fixed. The two groups, each TREATED as a single SEQUENCE, are then aligned to each other using global dynamic programming. The process is repeated through MANY cycles until the total SP score no longer increases. At this point, the resulting alignment is used to construct a new UPGMA tree.

Right choice is (c) The global pair WISE alignment is not performed using the CLUSTAL program.

The explanation: The global pair wise alignment is performed using the Clustal program. The main difference is that, in processing a query, T-Coffee performs both global and local pair wise alignment for all possible pairs involved. The collection of local and global sequence ALIGNMENTS is pooled to FORM a library. The consistency of the alignments is evaluated.

The correct ANSWER is (B) inner, OUTERMOST

For explanation I would say: Progenitor SEQUENCES represented by the inner branches of the tree are derived by alignment of the outermost sequences. These inner branches will have uncertainties where positions in the outermost sequences are DISSIMILAR.

Right choice is (d) If the sections are not short enough, further divisions are restricted as well

The best I can explain: This is a web-based program that is in fact semi exhaustive because certain STEPS of computation are REDUCED to heuristics. If the sections are not short enough, further divisions are carried out. When the lengths of the sequences reach a predefined threshold, DYNAMIC programming is applied for aligning each set of subsequences. The resulting short alignments are joined together head to TAIL to yield a multiple ALIGNMENT of the entire length of all sequences.

Correct answer is (b) small, almost identical

The explanation is: The number of sequences for producing the MOTIF may be small, highly diverse, or COMPLEX, GIVING rise to a second level of consideration. If the data set is small, then unless the motif has almost identical amino acids in each column, the column frequencies in the motif may not be highly representative of all other occurrences of the motif. In such cases, it is desirable to improve the estimates of the amino acid frequencies by adding extra amino acid counts, called pseudocounts, to OBTAIN a more reasonable DISTRIBUTION of amino acid frequencies in the column.

The correct answer is (a) True

Best explanation: A version of the Profilesearch program, which performs a database search for matches to a profile, is available at the University of Pittsburgh Supercomputer CENTER. A special GRANT application may be NEEDED to use this FACILITY. Profile-generating programs are available by FTP and are included in the Genetics Computer Group suite of programs.

The correct option is (C) weighting

Explanation: The W in CLUSTALW stands for ‘weighting’ to REPRESENT the ability of the program to provide weights to the SEQUENCE and program parameters. CLUSTAL has been around for more than 10 YEARS and lots of improvements in the program have been made.

The correct answer is (d) They are significantly quite less COMPLEX than DNA scoring matrices

For explanation I WOULD say: Protein substitution matrices are significantly more complex than DNA scoring matrices. Proteins are composed of twenty amino acids, and physico-chemical PROPERTIES of individual amino acids vary considerably. A protein substitution matrix can be BASED on any property of amino acids: size, polarity, CHARGE, hydrophobicity.

The correct ANSWER is (b) It is designed to detect global similarities

To elaborate: High-scoring segments, called blocks, AMONG different sequences are then compiled in a progressive manner to ASSEMBLE a full multiple alignment. It places emphasis on block-to-block comparison rather than residue-to-residue comparison. The sequence regions between the blocks are left unaligned. The program has been shown to be especially suitable for aligning divergent sequences with only LOCAL SIMILARITY.

The correct choice is (d) disallowing shading conserved residues in the alignment

The best I can explain: In addition to this, provision of a SUITABLE WINDOWS interface, allowing USE of the mouse to add, delete, or move sequence followed by an UPDATED display of the alignment, is a feature. In addition, there are other types of editing that are COMMONLY performed on MSAs (Multiple Sequence Alignment) program such as, for example, shading conserved residues in the alignment.

Correct choice is (a) True

To explain I would say: The analysis of MSAS (Multiple Sequence ALIGNMENT) for conserved blocks of sequence leads to production of the position-specific scoring matrix or PSSM. The PSSM may be used to SEARCH a sequence to obtain the most probable location or locations of the motif represented by the PSSM. Alternatively, the PSSM may be used to search an entire database to identify additional sequences that also have the same motif.