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      Nonparametric Method for Genomics-Based Prediction of Performance of Quantitative Traits Involving Epistasis in Plant Breeding

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          Abstract

          Genomic selection (GS) procedures have proven useful in estimating breeding value and predicting phenotype with genome-wide molecular marker information. However, issues of high dimensionality, multicollinearity, and the inability to deal effectively with epistasis can jeopardize accuracy and predictive ability. We, therefore, propose a new nonparametric method, pRKHS, which combines the features of supervised principal component analysis (SPCA) and reproducing kernel Hilbert spaces (RKHS) regression, with versions for traits with no/low epistasis, pRKHS-NE, to high epistasis, pRKHS-E. Instead of assigning a specific relationship to represent the underlying epistasis, the method maps genotype to phenotype in a nonparametric way, thus requiring fewer genetic assumptions. SPCA decreases the number of markers needed for prediction by filtering out low-signal markers with the optimal marker set determined by cross-validation. Principal components are computed from reduced marker matrix (called supervised principal components, SPC) and included in the smoothing spline ANOVA model as independent variables to fit the data. The new method was evaluated in comparison with current popular methods for practicing GS, specifically RR-BLUP, BayesA, BayesB, as well as a newer method by Crossa et al., RKHS-M, using both simulated and real data. Results demonstrate that pRKHS generally delivers greater predictive ability, particularly when epistasis impacts trait expression. Beyond prediction, the new method also facilitates inferences about the extent to which epistasis influences trait expression.

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          Most cited references18

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          Genomic-assisted prediction of genetic value with semiparametric procedures.

          Semiparametric procedures for prediction of total genetic value for quantitative traits, which make use of phenotypic and genomic data simultaneously, are presented. The methods focus on the treatment of massive information provided by, e.g., single-nucleotide polymorphisms. It is argued that standard parametric methods for quantitative genetic analysis cannot handle the multiplicity of potential interactions arising in models with, e.g., hundreds of thousands of markers, and that most of the assumptions required for an orthogonal decomposition of variance are violated in artificial and natural populations. This makes nonparametric procedures attractive. Kernel regression and reproducing kernel Hilbert spaces regression procedures are embedded into standard mixed-effects linear models, retaining additive genetic effects under multivariate normality for operational reasons. Inferential procedures are presented, and some extensions are suggested. An example is presented, illustrating the potential of the methodology. Implementations can be carried out after modification of standard software developed by animal breeders for likelihood-based or Bayesian analysis.
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            Reproducing kernel hilbert spaces regression methods for genomic assisted prediction of quantitative traits.

            Reproducing kernel Hilbert spaces regression procedures for prediction of total genetic value for quantitative traits, which make use of phenotypic and genomic data simultaneously, are discussed from a theoretical perspective. It is argued that a nonparametric treatment may be needed for capturing the multiple and complex interactions potentially arising in whole-genome models, i.e., those based on thousands of single-nucleotide polymorphism (SNP) markers. After a review of reproducing kernel Hilbert spaces regression, it is shown that the statistical specification admits a standard mixed-effects linear model representation, with smoothing parameters treated as variance components. Models for capturing different forms of interaction, e.g., chromosome-specific, are presented. Implementations can be carried out using software for likelihood-based or Bayesian inference.
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              Accuracy of genomic selection using different methods to define haplotypes.

              Genomic selection uses total breeding values for juvenile animals, predicted from a large number of estimated marker haplotype effects across the whole genome. In this study the accuracy of predicting breeding values is compared for four different models including a large number of markers, at different marker densities for traits with heritabilities of 50 and 10%. The models estimated the effect of (1) each single-marker allele [single-nucleotide polymorphism (SNP)1], (2) haplotypes constructed from two adjacent marker alleles (SNP2), and (3) haplotypes constructed from 2 or 10 markers, including the covariance between haplotypes by combining linkage disequilibrium and linkage analysis (HAP_IBD2 and HAP_IBD10). Between 119 and 2343 polymorphic SNPs were simulated on a 3-M genome. For the trait with a heritability of 10%, the differences between models were small and none of them yielded the highest accuracies across all marker densities. For the trait with a heritability of 50%, the HAP_IBD10 model yielded the highest accuracies of estimated total breeding values for juvenile and phenotyped animals at all marker densities. It was concluded that genomic selection is considerably more accurate than traditional selection, especially for a low-heritability trait.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                30 November 2012
                : 7
                : 11
                : e50604
                Affiliations
                [1 ]Department of Crop Sciences and the Illinois Plant Breeding Center, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                [2 ]Department of Statistics; University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
                Cleveland Clinic Lerner Research Institute, United States of America
                Author notes

                Competing Interests: Monsanto Company provided funding, which was used to support a fellowship (including annual stipend) for graduate student and first author XS. However, this funding was provided as a gift to the University of Illinois at Urbana-Champaign and Monsanto did not have any part in selection of XS as a fellowship awardee. Monsanto did/does not have any involvement in the conduct of this study or ownership in the data or results that were produced in the work outlined in this paper. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: XS RHM. Performed the experiments: XS. Analyzed the data: XS PM RHM. Contributed reagents/materials/analysis tools: XS RHM. Wrote the paper: XS PM RHM.

                [¤]

                Current address: Dow AgroSciences, Indianapolis, Indiana, United States of America

                Article
                PONE-D-12-24974
                10.1371/journal.pone.0050604
                3511520
                23226325
                6c00b031-5f9b-4bb7-a521-250c85e6c8a9
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 August 2012
                : 25 October 2012
                Page count
                Pages: 11
                Funding
                X. Sun was supported in his graduate studies as a Monsanto Fellow in Plant Breeding through a gift from Monsanto Company to the University of Illinois. P. Ma was supported by the National Science Foundation grant DMS 0800631, CAREER award DMS 1055815, and the Office of Science (BER), U.S. Department of Energy. R.H. Mumm was supported in part by the Agriculture and Food Research Initiative Competitive from the USDA National Institute of Food and Agriculture, grant award 2010-85117-20532, with additional funding from Hatch, award ILLU-802-354. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Agriculture
                Agricultural Biotechnology
                Marker-Assisted Selection
                Biology
                Computational Biology
                Genomics
                Genome Analysis Tools
                Trait Locus Analysis
                Population Modeling
                Plant Science
                Agronomy
                Plant Breeding
                Computer Science
                Computerized Simulations
                Mathematics
                Statistics
                Statistical Methods

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                Uncategorized

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