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Back-translation for discovering distant protein homologies in the presence of frameshift mutations.

Girdea M, Noe L, Kucherov G - Algorithms Mol Biol (2010)

Bottom Line: Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin.Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level.We developed a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences.

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ABSTRACT

Background: Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level.

Results: We developed a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. Our implementation is freely available at [http://bioinfo.lifl.fr/path/].

Conclusions: Our approach allows to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.

No MeSH data available.


Alignment example. A path (corresponding to a putative DNA sequence) was chosen from each graph so that the match/mismatch ratio is maximized.
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Figure 4: Alignment example. A path (corresponding to a putative DNA sequence) was chosen from each graph so that the match/mismatch ratio is maximized.

Mentions: Given input graphs GA and GB obtained by back-translating proteins PA and PB, the algorithm finds the best scoring local alignment between two DNA sequences comprised in the back-translation graphs (illustrated in Figure 4). The alignment is built by filling each entry M [i, j, (αi, βj)] of a dynamic programming matrix M, where i and j are positions of GA and GB respectively, and (αi, βj) enumerates the possible pairs of nodes that can be found in GA at position i, and in GB at position j, respectively. An example of matrix M is given in Figure 5.


Back-translation for discovering distant protein homologies in the presence of frameshift mutations.

Girdea M, Noe L, Kucherov G - Algorithms Mol Biol (2010)

Alignment example. A path (corresponding to a putative DNA sequence) was chosen from each graph so that the match/mismatch ratio is maximized.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821327&req=5

Figure 4: Alignment example. A path (corresponding to a putative DNA sequence) was chosen from each graph so that the match/mismatch ratio is maximized.
Mentions: Given input graphs GA and GB obtained by back-translating proteins PA and PB, the algorithm finds the best scoring local alignment between two DNA sequences comprised in the back-translation graphs (illustrated in Figure 4). The alignment is built by filling each entry M [i, j, (αi, βj)] of a dynamic programming matrix M, where i and j are positions of GA and GB respectively, and (αi, βj) enumerates the possible pairs of nodes that can be found in GA at position i, and in GB at position j, respectively. An example of matrix M is given in Figure 5.

Bottom Line: Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin.Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level.We developed a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Frameshift mutations in protein-coding DNA sequences produce a drastic change in the resulting protein sequence, which prevents classic protein alignment methods from revealing the proteins' common origin. Moreover, when a large number of substitutions are additionally involved in the divergence, the homology detection becomes difficult even at the DNA level.

Results: We developed a novel method to infer distant homology relations of two proteins, that accounts for frameshift and point mutations that may have affected the coding sequences. We design a dynamic programming alignment algorithm over memory-efficient graph representations of the complete set of putative DNA sequences of each protein, with the goal of determining the two putative DNA sequences which have the best scoring alignment under a powerful scoring system designed to reflect the most probable evolutionary process. Our implementation is freely available at [http://bioinfo.lifl.fr/path/].

Conclusions: Our approach allows to uncover evolutionary information that is not captured by traditional alignment methods, which is confirmed by biologically significant examples.

No MeSH data available.