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      RDP3: a flexible and fast computer program for analyzing recombination

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          Abstract

          Summary: RDP3 is a new version of the RDP program for characterizing recombination events in DNA-sequence alignments. Among other novelties, this version includes four new recombination analysis methods (3SEQ, VISRD, PHYLRO and LDHAT), new tests for recombination hot-spots, a range of matrix methods for visualizing over-all patterns of recombination within datasets and recombination-aware ancestral sequence reconstruction. Complementary to a high degree of analysis flow automation, RDP3 also has a highly interactive and detailed graphical user interface that enables more focused hands-on cross-checking of results with a wide variety of newly implemented phylogenetic tree construction and matrix-based recombination signal visualization methods. The new RDP3 can accommodate large datasets and is capable of analyzing alignments ranging in size from 1000×10 kilobase sequences to 20×2 megabase sequences within 48 h on a desktop PC.

          Availability: RDP3 is available for free from its web site http://darwin.uvigo.es/rdp/rdp.html

          Contact: darrenpatrickmartin@ 123456gmail.com

          Supplementary information: The RDP3 program manual contains detailed descriptions of the various methods it implements and a step-by-step guide describing how best to use these.

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          Multiple sequence alignment with the Clustal series of programs.

          R Chenna (2003)
          The Clustal series of programs are widely used in molecular biology for the multiple alignment of both nucleic acid and protein sequences and for preparing phylogenetic trees. The popularity of the programs depends on a number of factors, including not only the accuracy of the results, but also the robustness, portability and user-friendliness of the programs. New features include NEXUS and FASTA format output, printing range numbers and faster tree calculation. Although, Clustal was originally developed to run on a local computer, numerous Web servers have been set up, notably at the EBI (European Bioinformatics Institute) (http://www.ebi.ac.uk/clustalw/).
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            Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination.

            K Lole, R Bollinger, R S Paranjape … (1999)
            The development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-genome data are particularly limited for HIV-1 subtype C, currently the most commonly transmitted subtype in India and worldwide. Likewise, little is known about sequence variation of HIV-1 in India, the country facing the largest burden of HIV worldwide. Therefore, the objective of this study was to clone and characterize the complete genome of HIV-1 from seroconverters infected with subtype C variants in India. Cocultured HIV-1 isolates were obtained from six seroincident individuals from Pune, India, and virtually full-length HIV-1 genomes were amplified, cloned, and sequenced from each. Sequence analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, nef, and the 3' long terminal repeat as determined by both maximal chi2 analysis and phylogenetic bootstrapping. Sequences were compared for preservation of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-1LAI sequence, 38% of well-defined CTL epitopes were identical. The proportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, characterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env. Because these clones were obtained from Indian seroconverters, they are likely to facilitate vaccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.
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              The fine-scale structure of recombination rate variation in the human genome.

              Gilean McVean, Simon Myers, Sarah Hunt … (2004)
              The nature and scale of recombination rate variation are largely unknown for most species. In humans, pedigree analysis has documented variation at the chromosomal level, and sperm studies have identified specific hotspots in which crossing-over events cluster. To address whether this picture is representative of the genome as a whole, we have developed and validated a method for estimating recombination rates from patterns of genetic variation. From extensive single-nucleotide polymorphism surveys in European and African populations, we find evidence for extreme local rate variation spanning four orders in magnitude, in which 50% of all recombination events take place in less than 10% of the sequence. We demonstrate that recombination hotspots are a ubiquitous feature of the human genome, occurring on average every 200 kilobases or less, but recombination occurs preferentially outside genes.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Bioinformatics
                Journal ID (publisher-id): bioinformatics
                Journal ID (hwp): bioinfo
                Title: Bioinformatics
                Publisher: Oxford University Press
                ISSN (Print): 1367-4803
                ISSN (Electronic): 1367-4811
                Publication date (Print): 1 October 2010
                Publication date (Electronic): 26 August 2010
                Publication date PMC-release: 26 August 2010
                Volume: 26
                Issue: 19
                Pages: 2462-2463
                Affiliations
                1Computational Biology Group, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 2Centre for High Performance Computing, Rosebank, Cape Town, South Africa, 3Department of Microbiology and Immunology, Rega Institute, K.U. Leuven, Belgium, 4School of Computing Sciences, University of East Anglia, Norwich, NR4 7TJ, UK, 5Department of Biochemistry, Genetics and Immunology, University of Vigo, Spain and 6CIRAD, UMR 53 PVBMT CIRAD-Université de la Réunion, Pôle de Protection des Plantes, Ligne Paradis, La Réunion
                Author notes
                * To whom correspondence should be addressed.

                Associate Editor: Martin Bishop

                Article
                Publisher ID: btq467
                DOI: 10.1093/bioinformatics/btq467
                PMC ID: 2944210
                PubMed ID: 20798170
                SO-VID: fdbdc28a-85b6-4ebd-8955-fea8d8e04088
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 5 July 2010
                Date revision received : 8 August 2010
                Date accepted : 10 August 2010
                Categories
                Subject: Applications Note
                Subject: Sequence Analysis

                ScienceOpen disciplines: Bioinformatics & Computational biology
                Data availability:
                ScienceOpen disciplines: Bioinformatics & Computational biology

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