An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1.
Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1) are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such subtypes is helpful in surveillance, epidemiological analysis and d...
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Public Library of Science (PLoS)
2009
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oai:doaj.org-article:36c297325bc346a0ad203065bddcc9b62021-11-25T05:42:50ZAn evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1.1553-734X1553-735810.1371/journal.pcbi.1000581https://doaj.org/article/36c297325bc346a0ad203065bddcc9b62009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19956739/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1) are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such subtypes is helpful in surveillance, epidemiological analysis and detection of novel variants, e.g., circulating recombinant forms in HIV-1. A number of conceptually and technically different techniques have been proposed for determining the subtype of a query sequence, but there is not a universally optimal approach. We present a model-based phylogenetic method for automatically subtyping an HIV-1 (or other viral or bacterial) sequence, mapping the location of breakpoints and assigning parental sequences in recombinant strains as well as computing confidence levels for the inferred quantities. Our Subtype Classification Using Evolutionary ALgorithms (SCUEAL) procedure is shown to perform very well in a variety of simulation scenarios, runs in parallel when multiple sequences are being screened, and matches or exceeds the performance of existing approaches on typical empirical cases. We applied SCUEAL to all available polymerase (pol) sequences from two large databases, the Stanford Drug Resistance database and the UK HIV Drug Resistance Database. Comparing with subtypes which had previously been assigned revealed that a minor but substantial (approximately 5%) fraction of pure subtype sequences may in fact be within- or inter-subtype recombinants. A free implementation of SCUEAL is provided as a module for the HyPhy package and the Datamonkey web server. Our method is especially useful when an accurate automatic classification of an unknown strain is desired, and is positioned to complement and extend faster but less accurate methods. Given the increasingly frequent use of HIV subtype information in studies focusing on the effect of subtype on treatment, clinical outcome, pathogenicity and vaccine design, the importance of accurate, robust and extensible subtyping procedures is clear.Sergei L Kosakovsky PondDavid PosadaEric StawiskiColombe ChappeyArt F Y PoonGareth HughesEsther FearnhillMike B GravenorAndrew J Leigh BrownSimon D W FrostPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 11, p e1000581 (2009) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Sergei L Kosakovsky Pond David Posada Eric Stawiski Colombe Chappey Art F Y Poon Gareth Hughes Esther Fearnhill Mike B Gravenor Andrew J Leigh Brown Simon D W Frost An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. |
| description |
Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1) are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such subtypes is helpful in surveillance, epidemiological analysis and detection of novel variants, e.g., circulating recombinant forms in HIV-1. A number of conceptually and technically different techniques have been proposed for determining the subtype of a query sequence, but there is not a universally optimal approach. We present a model-based phylogenetic method for automatically subtyping an HIV-1 (or other viral or bacterial) sequence, mapping the location of breakpoints and assigning parental sequences in recombinant strains as well as computing confidence levels for the inferred quantities. Our Subtype Classification Using Evolutionary ALgorithms (SCUEAL) procedure is shown to perform very well in a variety of simulation scenarios, runs in parallel when multiple sequences are being screened, and matches or exceeds the performance of existing approaches on typical empirical cases. We applied SCUEAL to all available polymerase (pol) sequences from two large databases, the Stanford Drug Resistance database and the UK HIV Drug Resistance Database. Comparing with subtypes which had previously been assigned revealed that a minor but substantial (approximately 5%) fraction of pure subtype sequences may in fact be within- or inter-subtype recombinants. A free implementation of SCUEAL is provided as a module for the HyPhy package and the Datamonkey web server. Our method is especially useful when an accurate automatic classification of an unknown strain is desired, and is positioned to complement and extend faster but less accurate methods. Given the increasingly frequent use of HIV subtype information in studies focusing on the effect of subtype on treatment, clinical outcome, pathogenicity and vaccine design, the importance of accurate, robust and extensible subtyping procedures is clear. |
| format |
article |
| author |
Sergei L Kosakovsky Pond David Posada Eric Stawiski Colombe Chappey Art F Y Poon Gareth Hughes Esther Fearnhill Mike B Gravenor Andrew J Leigh Brown Simon D W Frost |
| author_facet |
Sergei L Kosakovsky Pond David Posada Eric Stawiski Colombe Chappey Art F Y Poon Gareth Hughes Esther Fearnhill Mike B Gravenor Andrew J Leigh Brown Simon D W Frost |
| author_sort |
Sergei L Kosakovsky Pond |
| title |
An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. |
| title_short |
An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. |
| title_full |
An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. |
| title_fullStr |
An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. |
| title_full_unstemmed |
An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. |
| title_sort |
evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in hiv-1. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/36c297325bc346a0ad203065bddcc9b6 |
| work_keys_str_mv |
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