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Motif-Aware PRALINE: Improving the alignment of motif regions
Protein or DNA motifs are sequence regions which possess biological importance. These regions are often highly conserved among homologous sequences. The generation of multiple sequence alignments (MSAs) with a correct alignment of the conserved sequence motifs is still difficult to achieve, due to t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233922/ https://www.ncbi.nlm.nih.gov/pubmed/30383764 http://dx.doi.org/10.1371/journal.pcbi.1006547 |
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author | Dijkstra, Maurits Bawono, Punto Abeln, Sanne Feenstra, K. Anton Fokkink, Wan Heringa, Jaap |
author_facet | Dijkstra, Maurits Bawono, Punto Abeln, Sanne Feenstra, K. Anton Fokkink, Wan Heringa, Jaap |
author_sort | Dijkstra, Maurits |
collection | PubMed |
description | Protein or DNA motifs are sequence regions which possess biological importance. These regions are often highly conserved among homologous sequences. The generation of multiple sequence alignments (MSAs) with a correct alignment of the conserved sequence motifs is still difficult to achieve, due to the fact that the contribution of these typically short fragments is overshadowed by the rest of the sequence. Here we extended the PRALINE multiple sequence alignment program with a novel motif-aware MSA algorithm in order to address this shortcoming. This method can incorporate explicit information about the presence of externally provided sequence motifs, which is then used in the dynamic programming step by boosting the amino acid substitution matrix towards the motif. The strength of the boost is controlled by a parameter, α. Using a benchmark set of alignments we confirm that a good compromise can be found that improves the matching of motif regions while not significantly reducing the overall alignment quality. By estimating α on an unrelated set of reference alignments we find there is indeed a strong conservation signal for motifs. A number of typical but difficult MSA use cases are explored to exemplify the problems in correctly aligning functional sequence motifs and how the motif-aware alignment method can be employed to alleviate these problems. |
format | Online Article Text |
id | pubmed-6233922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62339222018-11-19 Motif-Aware PRALINE: Improving the alignment of motif regions Dijkstra, Maurits Bawono, Punto Abeln, Sanne Feenstra, K. Anton Fokkink, Wan Heringa, Jaap PLoS Comput Biol Research Article Protein or DNA motifs are sequence regions which possess biological importance. These regions are often highly conserved among homologous sequences. The generation of multiple sequence alignments (MSAs) with a correct alignment of the conserved sequence motifs is still difficult to achieve, due to the fact that the contribution of these typically short fragments is overshadowed by the rest of the sequence. Here we extended the PRALINE multiple sequence alignment program with a novel motif-aware MSA algorithm in order to address this shortcoming. This method can incorporate explicit information about the presence of externally provided sequence motifs, which is then used in the dynamic programming step by boosting the amino acid substitution matrix towards the motif. The strength of the boost is controlled by a parameter, α. Using a benchmark set of alignments we confirm that a good compromise can be found that improves the matching of motif regions while not significantly reducing the overall alignment quality. By estimating α on an unrelated set of reference alignments we find there is indeed a strong conservation signal for motifs. A number of typical but difficult MSA use cases are explored to exemplify the problems in correctly aligning functional sequence motifs and how the motif-aware alignment method can be employed to alleviate these problems. Public Library of Science 2018-11-01 /pmc/articles/PMC6233922/ /pubmed/30383764 http://dx.doi.org/10.1371/journal.pcbi.1006547 Text en © 2018 Dijkstra et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Dijkstra, Maurits Bawono, Punto Abeln, Sanne Feenstra, K. Anton Fokkink, Wan Heringa, Jaap Motif-Aware PRALINE: Improving the alignment of motif regions |
title | Motif-Aware PRALINE: Improving the alignment of motif regions |
title_full | Motif-Aware PRALINE: Improving the alignment of motif regions |
title_fullStr | Motif-Aware PRALINE: Improving the alignment of motif regions |
title_full_unstemmed | Motif-Aware PRALINE: Improving the alignment of motif regions |
title_short | Motif-Aware PRALINE: Improving the alignment of motif regions |
title_sort | motif-aware praline: improving the alignment of motif regions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233922/ https://www.ncbi.nlm.nih.gov/pubmed/30383764 http://dx.doi.org/10.1371/journal.pcbi.1006547 |
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