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doi:10.1534/genetics.106.066258
A more recent version of this article appeared on April 1, 2007.
REGULAR RESEARCH PAPERS |
Phylogenetic Mapping of Recombination Hot-Spots in HIV via Spatially Smoothed Change-Point Processes
Vladimir N. Minin 1, Karin S. Dorman 2, Fang Fang 2 and Marc A. Suchard 1*
1 David Geffen School of Medicine at UCLA
2 Iowa State University
* To whom correspondence should be addressed. E-mail: msuchard{at}ucla.edu.
Submitted on September 29, 2006
Revised on December 4, 2006
Accepted on 22 December 2006
We present a Bayesian framework for inferring spatial preferences of recombination from multiple putative recombinant nucleotide sequences. Phylogenetic recombination detection has been an active area of research for the last 15 years. However, only recently attempts of summarizing information from several instances of recombination have been made. We propose a hierarchical model that allows for simultaneous inference of recombination break-point locations and spatial variation in recombination frequency. The dual multiple change-point model for phylogenetic recombination detection resides at the lowest level of our hierarchy under the umbrella of a common prior on break-point locations. The hierarchical prior allows for information about spatial preferences of recombination to be shared among individual datasets. To overcome the sparseness of break-point data, dictated by the modest number of available recombinant sequences, we a priori impose a biologically relevant correlation structure on recombination location log-odds via a Gaussian Markov random field hyper-prior. To examine the capabilities of our model to recover spatial variation in recombination frequency, we simulate recombination from a predefined distribution of break-point locations. We then proceed with the analysis of 42 HIV intersubtype gag recombinants and identify a putative recombination hot-spot.
Key Words: Change-point model, Gaussian Markov random field, HIV, Phylogenetics, Recombination
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