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      Genome scans for detecting footprints of local adaptation using a Bayesian factor model

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          Abstract

          A central part of population genomics consists of finding genomic regions implicated in local adaptation. Population genomic analyses are based on genotyping numerous molecular markers and looking for outlier loci in terms of patterns of genetic differentiation. One of the most common approach for selection scan is based on statistics that measure population differentiation such as \(F_{ST}\). However they are important caveats with approaches related to \(F_{ST}\) because they require grouping individuals into populations and they additionally assume a particular model of population structure. Here we implement a more flexible individual-based approach based on Bayesian factor models. Factor models capture population structure with latent variables called factors, which can describe clustering of individuals into populations or isolation-by-distance patterns. Using hierarchical Bayesian modeling, we both infer population structure and identify outlier loci that are candidates for local adaptation. As outlier loci, the hierarchical factor model searches for loci that are atypically related to population structure as measured by the latent factors. In a model of population divergence, we show that the factor model can achieve a 2-fold or more reduction of false discovery rate compared to the software BayeScan or compared to a \(F_{ST}\) approach. We analyze the data of the Human Genome Diversity Panel to provide an example of how factor models can be used to detect local adaptation with a large number of SNPs. The Bayesian factor model is implemented in the open-source PCAdapt software.

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          Interpreting principal component analyses of spatial population genetic variation.

          Nearly 30 years ago, Cavalli-Sforza et al. pioneered the use of principal component analysis (PCA) in population genetics and used PCA to produce maps summarizing human genetic variation across continental regions. They interpreted gradient and wave patterns in these maps as signatures of specific migration events. These interpretations have been controversial, but influential, and the use of PCA has become widespread in analysis of population genetics data. However, the behavior of PCA for genetic data showing continuous spatial variation, such as might exist within human continental groups, has been less well characterized. Here, we find that gradients and waves observed in Cavalli-Sforza et al.'s maps resemble sinusoidal mathematical artifacts that arise generally when PCA is applied to spatial data, implying that the patterns do not necessarily reflect specific migration events. Our findings aid interpretation of PCA results and suggest how PCA can help correct for continuous population structure in association studies.
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            A Bayesian missing value estimation method for gene expression profile data.

            Gene expression profile analyses have been used in numerous studies covering a broad range of areas in biology. When unreliable measurements are excluded, missing values are introduced in gene expression profiles. Although existing multivariate analysis methods have difficulty with the treatment of missing values, this problem has received little attention. There are many options for dealing with missing values, each of which reaches drastically different results. Ignoring missing values is the simplest method and is frequently applied. This approach, however, has its flaws. In this article, we propose an estimation method for missing values, which is based on Bayesian principal component analysis (BPCA). Although the methodology that a probabilistic model and latent variables are estimated simultaneously within the framework of Bayes inference is not new in principle, actual BPCA implementation that makes it possible to estimate arbitrary missing variables is new in terms of statistical methodology. When applied to DNA microarray data from various experimental conditions, the BPCA method exhibited markedly better estimation ability than other recently proposed methods, such as singular value decomposition and K-nearest neighbors. While the estimation performance of existing methods depends on model parameters whose determination is difficult, our BPCA method is free from this difficulty. Accordingly, the BPCA method provides accurate and convenient estimation for missing values. The software is available at http://hawaii.aist-nara.ac.jp/~shige-o/tools/.
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              Genome-wide scans for footprints of natural selection

              Detecting recent selected ‘genomic footprints’ applies directly to the discovery of disease genes and in the imputation of the formative events that molded modern population genetic structure. The imprints of historic selection/adaptation episodes left in human and animal genomes allow one to interpret modern and ancestral gene origins and modifications. Current approaches to reveal selected regions applied in genome-wide selection scans (GWSSs) fall into eight principal categories: (I) phylogenetic footprinting, (II) detecting increased rates of functional mutations, (III) evaluating divergence versus polymorphism, (IV) detecting extended segments of linkage disequilibrium, (V) evaluating local reduction in genetic variation, (VI) detecting changes in the shape of the frequency distribution (spectrum) of genetic variation, (VII) assessing differentiating between populations (F ST), and (VIII) detecting excess or decrease in admixture contribution from one population. Here, we review and compare these approaches using available human genome-wide datasets to provide independent verification (or not) of regions found by different methods and using different populations. The lessons learned from GWSSs will be applied to identify genome signatures of historic selective pressures on genes and gene regions in other species with emerging genome sequences. This would offer considerable potential for genome annotation in functional, developmental and evolutionary contexts.
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                Author and article information

                Journal
                2014-02-21
                2014-02-26
                Article
                1402.5321
                860651f4-4180-4ecc-9c61-aae80d40a88a

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

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                Custom metadata
                62P10
                q-bio.PE stat.AP

                Evolutionary Biology,Applications
                Evolutionary Biology, Applications

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