Phylogenetic mapping of recombination hotspots in human immunodeficiency virus via spatially smoothed change-point processes

被引:27
作者
Minin, Vladimir N.
Dorman, Karin S.
Fang, Fang
Suchard, Marc A.
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA
[4] Iowa State Univ, Bioinformat & Computat Biol Program, Ames, IA 50011 USA
[5] Iowa State Univ, Dept Stat, Ames, IA 50011 USA
[6] Iowa State Univ, Dept Genet Cell & Dev Biol, Ames, IA 50011 USA
关键词
D O I
10.1534/genetics.106.066258
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 to summarize information from several instances of recombination have been made. We propose a hierarchical model that allows for simultaneous inference of recombination breakpoint 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 breakpoint locations. The hierarchical prior allows for information about spatial preferences of recombination to be shared among individual data sets. To overcome the sparseness of breakpoint 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 hyperprior. To examine the capabilities of our model to recover spatial variation in recombination frequency, we simulate recombination from a predefined distribution of breakpoint locations. We then proceed with the analysis of 42 human immunodeficiency virus (HIV) intersubtype gag recombinants and identify a putative recombination hotspot.
引用
收藏
页码:1773 / 1785
页数:13
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