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Raazesh Sainudiin
Lecturer in Statistics (akin to US Asst. Prof. Tenure Track), University of Canterbury
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Auto-validating von Neumann rejection sampling from small phylogenetic tree spaces.
Algorithms for molecular biology : AMB 2009 Jan; 4
BACKGROUND: In phylogenetic inference one is interested in obtaining samples from the posterior distribution over the tree space on the basis of some observed DNA sequence data. One of the simplest sampling methods is the rejection sampler due to von... expand abstract Neumann. Here we introduce an auto-validating version of the rejection sampler, via interval analysis, to rigorously draw samples from posterior distributions over small phylogenetic tree spaces. RESULTS: The posterior samples from the auto-validating sampler are used to rigorously (i) estimate posterior probabilities for different rooted topologies based on mitochondrial DNA from human, chimpanzee and gorilla, (ii) conduct a non-parametric test of rate variation between protein-coding and tRNA-coding sites from three primates and (iii) obtain a posterior estimate of the human-neanderthal divergence time. CONCLUSION: This solves the open problem of rigorously drawing independent and identically distributed samples from the posterior distribution over rooted and unrooted small tree spaces (3 or 4 taxa) based on any multiply-aligned sequence data. collapse abstract
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Simple models of genomic variation in human SNP density.
BMC genomics 2007 Jan; 8
BACKGROUND: Descriptive hierarchical Poisson models and population-genetic coalescent mixture models are used to describe the observed variation in single-nucleotide polymorphism (SNP) density from samples of size two across the human genome. RESULTS... expand abstract: Using empirical estimates of recombination rate across the human genome and the observed SNP density distribution, we produce a maximum likelihood estimate of the genomic heterogeneity in the scaled mutation rate theta. Such models produce significantly better fits to the observed SNP density distribution than those that ignore the empirically observed recombinational heterogeneities. CONCLUSION: Accounting for mutational and recombinational heterogeneities can allow for empirically sound null distributions in genome scans for "outliers", when the alternative hypotheses include fundamentally historical and unobserved phenomena. collapse abstract
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Relative Contribution of Seed-Transmitted Inoculum to Foliar Populations of Phaeosphaeria nodorum.
Phytopathology 2008 Oct; 97(5)
ABSTRACT A marked-isolate, release-recapture experiment was conducted to assess the relative contributions of seed-transmitted (released isolates) versus all other inocula to foliar and grain populations of Phaeosphaeria nodorum in winter wheat rotat... expand abstracted with nonsusceptible crops in New York and Georgia, United States. Seed infected with two distinct groups of marked isolates of P. nodorum containing rare alleles (identified by amplified fragment length polymorphisms [AFLPs]) and balanced for mating type were planted in experimental field plots in two locations in each state. Recapture was done by isolating P. nodorum from leaves showing necrotic lesions at spring tillering and flowering stages, and mature grains from spikes showing glume blotch. Isolates from these samples were genotyped by AFLPs and categorized as released or nonreleased to infer sources of inoculum. Both infected seed and other sources of the pathogen contributed significant primary inocula to populations recovered from leaves and harvested grain. Seed-transmitted genotypes accounted for a total of 57% of all isolates recovered from inoculated plots, with a range of 15 to 90% of the populations of P. nodorum collected over the season in individual, inoculated plots at the four locations. Plants in the noninoculated control plots also became diseased and 95% or more of the isolates recovered from these plots were nonreleased genotypes. Although other potential sources of P. nodorum within and adjacent to experimental plots were not ruled out, nonreleased genotypes likely were derived from immigrant ascospores potentially from sources at a considerable distance from the plots. Our results suggest that, although reduction of seedborne inoculum of P. nodorum may delay foliar epidemics, this strategy by itself is unlikely to result in high levels of control in eastern North America because of the additional contribution from alternative sources of inoculum. collapse abstract
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Auto-validating von Neumann Rejection Sampling from Small Phylogenetic Tree Spaces
2006 Dec;
In phylogenetic inference one is interested in obtaining samples from the posterior distribution over the tree space on the basis of some observed DNA sequence data. The challenge is to obtain samples from this target distribution without any knowl... expand abstractedge of the normalizing constant. One of the simplest sampling methods is the rejection sampler due to von Neumann. Here we introduce an auto-validating version of the rejection sampler, via interval analysis, to rigorously draw samples from posterior distributions, based on homologous primate mitochondrial DNA, over small phylogenetic tree spaces. collapse abstract
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An Auto-validating Rejection Sampler
2006 Nov;
In Bayesian statistical inference and computationally intensive frequentist inference, one is interested in obtaining samples from a high dimensional, and possibly multi-modal target density. The challenge is to obtain samples from this target with... expand abstractout any knowledge of the normalizing constant. Several approaches to this problem rely on Monte Carlo methods. One of the simplest such methods is the rejection sampler due to von Neumann. Here we introduce an auto-validating version of the rejection sampler via interval analysis. We show that our rejection sampler does provide us with independent samples from a large class of target densities in a guaranteed manner. We illustrate the efficiency of the sampler by theory and by examples in up to 10 dimensions. Our sampler is immune to the `pathologies' of some infamous densities including the witch's hat and can rigorously draw samples from piece-wise Euclidean spaces of small phylogenetic trees. collapse abstract
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Identification of physicochemical selective pressure on protein encoding nucleotide sequences.
BMC bioinformatics 2006 Jan; 7
BACKGROUND: Statistical methods for identifying positively selected sites in protein coding regions are one of the most commonly used tools in evolutionary bioinformatics. However, they have been limited by not taking the physiochemical properties of... expand abstract amino acids into account. RESULTS: We develop a new codon-based likelihood model for detecting site-specific selection pressures acting on specific physicochemical properties. Nonsynonymous substitutions are divided into substitutions that differ with respect to the physicochemical properties of interest, and those that do not. The substitution rates of these two types of changes, relative to the synonymous substitution rate, are then described by two parameters, gamma and omega respectively. The new model allows us to perform likelihood ratio tests for positive selection acting on specific physicochemical properties of interest.The new method is first used to analyze simulated data and is shown to have good power and accuracy in detecting physicochemical selective pressure. We then re-analyze data from the class-I alleles of the human Major Histocompatibility Complex (MHC) and from the abalone sperm lysine. CONCLUSION: Our new method allows a more flexible framework to identify selection pressure on particular physicochemical properties. collapse abstract
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Detecting site-specific physicochemical selective pressures: applications to the Class I HLA of the human major histocompatibility complex and the SRK of the plant sporophytic self-incompatibility system.
Journal of molecular evolution 2005 Mar; 60(3)
Models of codon substitution are developed that incorporate physicochemical properties of amino acids. When amino acid sites are inferred to be under positive selection, these models suggest the nature and extent of the physicochemical properties und... expand abstracter selection. This is accomplished by first partitioning the codons on the basis of some property of the encoded amino acids. This partition is used to parametrize the rates of property-conserving and property-altering base substitutions at the codon level by means of finite mixtures of Markov models that also account for codon and transition:transversion biases. Here, we apply this method to two positively selected receptors involved in ligand-recognition: the class I alleles of the human major histocompatibility complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the sporophytic self-incompatibility system (SSI) in cruciferous plants (Brassicaceae), whose structure is unknown. Through likelihood ratio tests we demonstrate that at some sites, the positively selected MHC and SRK proteins are under physicochemical selective pressures to alter polarity, volume, polarity and/or volume, and charge to various extents. An empirical Bayes approach is used to identify sites that may be important for ligand recognition in these proteins. collapse abstract
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Microsatellite mutation models: insights from a comparison of humans and chimpanzees.
Genetics 2004 Sep; 168(1)
Using genomic data from homologous microsatellite loci of pure AC repeats in humans and chimpanzees, several models of microsatellite evolution are tested and compared using likelihood-ratio tests and the Akaike information criterion. A proportional-... expand abstractrate, linear-biased, one-phase model emerges as the best model. A focal length toward which the mutational and/or substitutional process is linearly biased is a crucial feature of microsatellite evolution. We find that two-phase models do not lead to a significantly better fit than their one-phase counterparts. The performance of models based on the fit of their stationary distributions to the empirical distribution of microsatellite lengths in the human genome is consistent with that based on the human-chimp comparison. Microsatellites interrupted by even a single point mutation exhibit a twofold decrease in their mutation rate when compared to pure AC repeats. In general, models that allow chimps to have a larger per-repeat unit slippage rate and/or a shorter focal length compared to humans give a better fit to the human-chimp data as well as the human genomic data. collapse abstract