Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons
Profile hidden Markov models (HMMs) are a powerful way of modeling biological sequence diversity and constitute a very sensitive approach to detecting divergent sequences. Here, we report the development of protocols for the rational design of profile HMMs. These methods were implemented on TABAJARA...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/2/519 |
| _version_ | 1797617788198584320 |
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| author | Liliane S. Oliveira Alejandro Reyes Bas E. Dutilh Arthur Gruber |
| author_facet | Liliane S. Oliveira Alejandro Reyes Bas E. Dutilh Arthur Gruber |
| author_sort | Liliane S. Oliveira |
| collection | DOAJ |
| description | Profile hidden Markov models (HMMs) are a powerful way of modeling biological sequence diversity and constitute a very sensitive approach to detecting divergent sequences. Here, we report the development of protocols for the rational design of profile HMMs. These methods were implemented on TABAJARA, a program that can be used to either detect all biological sequences of a group or discriminate specific groups of sequences. By calculating position-specific information scores along a multiple sequence alignment, TABAJARA automatically identifies the most informative sequence motifs and uses them to construct profile HMMs. As a proof-of-principle, we applied TABAJARA to generate profile HMMs for the detection and classification of two viral groups presenting different evolutionary rates: bacteriophages of the <i>Microviridae</i> family and viruses of the <i>Flavivirus</i> genus. We obtained conserved models for the generic detection of any <i>Microviridae</i> or <i>Flavivirus</i> sequence, and profile HMMs that can specifically discriminate <i>Microviridae</i> subfamilies or <i>Flavivirus</i> species. In another application, we constructed Cas1 endonuclease-derived profile HMMs that can discriminate CRISPRs and casposons, two evolutionarily related transposable elements. We believe that the protocols described here, and implemented on TABAJARA, constitute a generic toolbox for generating profile HMMs for the highly sensitive and specific detection of sequence classes. |
| first_indexed | 2024-03-11T08:00:44Z |
| format | Article |
| id | doaj.art-6ea8278ddac74c389a5349c06d103afc |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T08:00:44Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-6ea8278ddac74c389a5349c06d103afc2023-11-16T23:50:07ZengMDPI AGViruses1999-49152023-02-0115251910.3390/v15020519Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and CasposonsLiliane S. Oliveira0Alejandro Reyes1Bas E. Dutilh2Arthur Gruber3Department of Parasitology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, SP, BrazilMax Planck Tandem Group in Computational Biology, Department of Biological Sciences, Universidad de los Andes, Bogotá 111711, ColombiaInstitute of Biodiversity, Faculty of Biological Sciences, Cluster of Excellence Balance of the Microverse, Friedrich-Schiller-University Jena, 07743 Jena, GermanyDepartment of Parasitology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, SP, BrazilProfile hidden Markov models (HMMs) are a powerful way of modeling biological sequence diversity and constitute a very sensitive approach to detecting divergent sequences. Here, we report the development of protocols for the rational design of profile HMMs. These methods were implemented on TABAJARA, a program that can be used to either detect all biological sequences of a group or discriminate specific groups of sequences. By calculating position-specific information scores along a multiple sequence alignment, TABAJARA automatically identifies the most informative sequence motifs and uses them to construct profile HMMs. As a proof-of-principle, we applied TABAJARA to generate profile HMMs for the detection and classification of two viral groups presenting different evolutionary rates: bacteriophages of the <i>Microviridae</i> family and viruses of the <i>Flavivirus</i> genus. We obtained conserved models for the generic detection of any <i>Microviridae</i> or <i>Flavivirus</i> sequence, and profile HMMs that can specifically discriminate <i>Microviridae</i> subfamilies or <i>Flavivirus</i> species. In another application, we constructed Cas1 endonuclease-derived profile HMMs that can discriminate CRISPRs and casposons, two evolutionarily related transposable elements. We believe that the protocols described here, and implemented on TABAJARA, constitute a generic toolbox for generating profile HMMs for the highly sensitive and specific detection of sequence classes.https://www.mdpi.com/1999-4915/15/2/519viral classificationviral detectionprofile HMMssequence classesmutual information theorysequence entropy |
| spellingShingle | Liliane S. Oliveira Alejandro Reyes Bas E. Dutilh Arthur Gruber Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons Viruses viral classification viral detection profile HMMs sequence classes mutual information theory sequence entropy |
| title | Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons |
| title_full | Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons |
| title_fullStr | Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons |
| title_full_unstemmed | Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons |
| title_short | Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons |
| title_sort | rational design of profile hmms for sensitive and specific sequence detection with case studies applied to viruses bacteriophages and casposons |
| topic | viral classification viral detection profile HMMs sequence classes mutual information theory sequence entropy |
| url | https://www.mdpi.com/1999-4915/15/2/519 |
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