HIV classification using the coalescent theory.
BACKGROUND
Existing coalescent models and phylogenetic tools based on them are not designed for studying the genealogy of sequences like those of HIV, since in HIV recombinants with multiple cross-over points between the parental strains frequently arise. Hence, ambiguous cases in the classification of HIV sequences into subtypes and circulating recombinant forms (CRFs) have been treated with ad hoc methods in lack of tools based on a comprehensive coalescent model accounting for complex recombination patterns.


RESULTS
We developed the program ARGUS that scores classifications of sequences into subtypes and recombinant forms. It reconstructs ancestral recombination graphs (ARGs) that reflect the genealogy of the input sequences given a classification hypothesis. An ARG with maximal probability is approximated using a Markov chain Monte Carlo approach. ARGUS was able to distinguish the correct classification with a low error rate from plausible alternative classifications in simulation studies with realistic parameters. We applied our algorithm to decide between two recently debated alternatives in the classification of CRF02 of HIV-1 and find that CRF02 is indeed a recombinant of Subtypes A and G.


BACKGROUND
ARGUS is implemented in C++ and the source code is available at http://gobics.de/software.
Bulla
Ingo
I
Abteilung Bioinformatik, Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Goldschmidtstrasse 1, 37077 Göttingen, Germany. ibulla@uni-goettingen.de
Schultz
Anne-Kathrin
AK
Schreiber
Fabian
F
Zhang
Ming
M
Leitner
Thomas
T
Korber
Bette
B
Morgenstern
Burkhard
B
Stanke
Mario
M
D000465:Algorithms; D006678:HIV / Q000145:classification* / Q000235:genetics; D015497:HIV-1 / Q000145:classification; D008390:Markov Chains; D010802:Phylogeny; D017422:Sequence Analysis, DNA
Science. 2003 Jun 13;300(5626):1713
12805540
J Gen Virol. 2005 Dec;86(Pt 12):3281-3290
16298973
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W463-5
16845050
Genetics. 2000 Nov;156(3):1393-401
11063710
Virology. 2001 May 10;283(2):161-6
11336541
J Virol. 1992 Dec;66(12):7576-80
1279208
BMC Bioinformatics. 2009 Apr 27;10:126
19397803
Proc Natl Acad Sci U S A. 1988 Aug;85(16):5997-6001
3413072
J Virol. 2000 Nov;74(22):10752-65
11044120
Nat Rev Genet. 2004 Jan;5(1):52-61
14708016
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7352-7
10377418
Genetics. 2005 Jan;169(1):21-35
15489535
Annu Rev Microbiol. 2001;55:561-90
11544367
J Virol. 2007 Aug;81(16):8543-51
17553886
J Virol. 1999 Jan;73(1):667-75
9847372
Bioinformatics. 2006 May 1;22(9):1064-71
16488909
EMBO J. 1992 Aug;11(8):3135-45
1379178
Virology. 1978 Jun 15;87(2):326-38
208279
J Virol. 1999 Jan;73(1):152-60
9847317
Theor Popul Biol. 1999 Jun;55(3):248-59
10366550
Bioinformatics. 2005 Oct 1;21(19):3797-800
16076886
Science. 2000 Apr 7;288(5463):55-6
10766634
Microbiol Rev. 1992 Mar;56(1):61-79
1579113
J Virol. 2002 Nov;76(22):11273-82
12388687
Bioinformatics. 2004 Feb 12;20(3):407-15
14960467
Theor Popul Biol. 1983 Apr;23(2):183-201
6612631
Bioinformatics. 2006 Mar 15;22(6):768-70
16410317
Virology. 1994 Oct;204(1):462-5
8091680
J Comput Biol. 2002;9(5):747-60
12487762
BMC Bioinformatics. 2006 May 22;7:265
16716226