Greedy de novo motif discovery to construct motif repositories for bacterial proteomes
Abstract Background Bacterial surfaces are complex systems, constructed from membranes, peptidoglycan and, importantly, proteins. The proteins play crucial roles as critical regulators of how the bacterium interacts with and survive in its environment. A full catalog of the motifs in protein familie...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12859-019-2686-8 |
| _version_ | 1818113814326935552 |
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| author | Hamed Khakzad Johan Malmström Lars Malmström |
| author_facet | Hamed Khakzad Johan Malmström Lars Malmström |
| author_sort | Hamed Khakzad |
| collection | DOAJ |
| description | Abstract Background Bacterial surfaces are complex systems, constructed from membranes, peptidoglycan and, importantly, proteins. The proteins play crucial roles as critical regulators of how the bacterium interacts with and survive in its environment. A full catalog of the motifs in protein families and their relative conservation grade is a prerequisite to target the protein-protein interaction that bacterial surface protein makes to host proteins. Results In this paper, we propose a greedy approach to identify conserved motifs in large sequence families iteratively. Each iteration discovers a motif de novo and masks all occurrences of that motif. Remaining unmasked sequences are subjected to the next round of motif detection until no more significant motifs can be found. We demonstrate the utility of the method through the construction of a proteome-wide motif repository for Group A Streptococcus (GAS), a significant human pathogen. GAS produce numerous surface proteins that interact with over 100 human plasma proteins, helping the bacteria to evade the host immune response. We used the repository to find that proteins part of the bacterial surface has motif architectures that differ from intracellular proteins. Conclusions We elucidate that the M protein, a coiled-coil homodimer that extends over 500 A from the cell wall, has a motif architecture that differs between various GAS strains. As the M protein is known to bind a variety of different plasma proteins, the results indicate that the different motif architectures are responsible for the quantitative differences of plasma proteins that various strains bind. The speed and applicability of the method enable its application to all major human pathogens. |
| first_indexed | 2024-12-11T03:40:49Z |
| format | Article |
| id | doaj.art-aa09d15c51a74dd98d92f94166d2e176 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-11T03:40:49Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-aa09d15c51a74dd98d92f94166d2e1762022-12-22T01:22:08ZengBMCBMC Bioinformatics1471-21052019-04-0120S411010.1186/s12859-019-2686-8Greedy de novo motif discovery to construct motif repositories for bacterial proteomesHamed Khakzad0Johan Malmström1Lars Malmström2Faculty of Science, Institute for Computational Science, University of ZurichDivision of Infection Medicine, Department of Clinical 432 Sciences, Lund UniversityFaculty of Science, Institute for Computational Science, University of ZurichAbstract Background Bacterial surfaces are complex systems, constructed from membranes, peptidoglycan and, importantly, proteins. The proteins play crucial roles as critical regulators of how the bacterium interacts with and survive in its environment. A full catalog of the motifs in protein families and their relative conservation grade is a prerequisite to target the protein-protein interaction that bacterial surface protein makes to host proteins. Results In this paper, we propose a greedy approach to identify conserved motifs in large sequence families iteratively. Each iteration discovers a motif de novo and masks all occurrences of that motif. Remaining unmasked sequences are subjected to the next round of motif detection until no more significant motifs can be found. We demonstrate the utility of the method through the construction of a proteome-wide motif repository for Group A Streptococcus (GAS), a significant human pathogen. GAS produce numerous surface proteins that interact with over 100 human plasma proteins, helping the bacteria to evade the host immune response. We used the repository to find that proteins part of the bacterial surface has motif architectures that differ from intracellular proteins. Conclusions We elucidate that the M protein, a coiled-coil homodimer that extends over 500 A from the cell wall, has a motif architecture that differs between various GAS strains. As the M protein is known to bind a variety of different plasma proteins, the results indicate that the different motif architectures are responsible for the quantitative differences of plasma proteins that various strains bind. The speed and applicability of the method enable its application to all major human pathogens.http://link.springer.com/article/10.1186/s12859-019-2686-8De novo motif discoveryInfectious diseasesGroup A streptococcus |
| spellingShingle | Hamed Khakzad Johan Malmström Lars Malmström Greedy de novo motif discovery to construct motif repositories for bacterial proteomes BMC Bioinformatics De novo motif discovery Infectious diseases Group A streptococcus |
| title | Greedy de novo motif discovery to construct motif repositories for bacterial proteomes |
| title_full | Greedy de novo motif discovery to construct motif repositories for bacterial proteomes |
| title_fullStr | Greedy de novo motif discovery to construct motif repositories for bacterial proteomes |
| title_full_unstemmed | Greedy de novo motif discovery to construct motif repositories for bacterial proteomes |
| title_short | Greedy de novo motif discovery to construct motif repositories for bacterial proteomes |
| title_sort | greedy de novo motif discovery to construct motif repositories for bacterial proteomes |
| topic | De novo motif discovery Infectious diseases Group A streptococcus |
| url | http://link.springer.com/article/10.1186/s12859-019-2686-8 |
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