| Autor: |
Oliveira LS; Department of Parasitology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil., Reyes A; Max Planck Tandem Group in Computational Biology, Department of Biological Sciences, Universidad de los Andes, Bogotá 111711, Colombia.; The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, MO 63108, USA., Dutilh BE; Institute of Biodiversity, Faculty of Biological Sciences, Cluster of Excellence Balance of the Microverse, Friedrich-Schiller-University Jena, 07743 Jena, Germany.; Theoretical Biology and Bioinformatics, Science for Life, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.; European Virus Bioinformatics Center, Leutragraben 1, 07743 Jena, Germany., Gruber A; Department of Parasitology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil.; European Virus Bioinformatics Center, Leutragraben 1, 07743 Jena, Germany. |
| Abstrakt: |
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 Microviridae family and viruses of the Flavivirus genus. We obtained conserved models for the generic detection of any Microviridae or Flavivirus sequence, and profile HMMs that can specifically discriminate Microviridae subfamilies or Flavivirus 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. |
