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797 result(s) for "de los Campos, Gustavo"
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Genomic Prediction of Breeding Values when Modeling Genotype × Environment Interaction using Pedigree and Dense Molecular Markers
Genomic selection (GS) has become an important aid in plant and animal breeding. Multienvironment (multitrait) models allow borrowing of information across environments (traits), which could enhance prediction accuracy. This study presents multienvironment (multitrait) models for GS and compares the predictive accuracy of these models with: (i) multienvironment analysis without pedigree and marker information, and (ii) multienvironment pedigree or/and marker-based models. A statistical framework for incorporating pedigree and molecular marker information in models for multienvironment data is described and applied to data that originate from wheat (Triticum aestivum L.) multienvironment trials. Two prediction problems relevant to plant breeders are considered: (CV1) predicting the performance of untested genotypes (“newly” developed lines), and (CV2) predicting the performance of genotypes that have been evaluated in some environments but not in others. Results confirmed the superiority of models using both marker and pedigree information over those based on pedigree information only. Models with pedigree and/or markers had better predictive accuracy than simple linear mixed models that do not include either of these two sources of information. We concluded that the evaluation of such trials can benefit greatly from using multienvironment GS models.
A data-driven simulation platform to predict cultivars’ performances under uncertain weather conditions
In most crops, genetic and environmental factors interact in complex ways giving rise to substantial genotype-by-environment interactions (G×E). We propose that computer simulations leveraging field trial data, DNA sequences, and historical weather records can be used to tackle the longstanding problem of predicting cultivars’ future performances under largely uncertain weather conditions. We present a computer simulation platform that uses Monte Carlo methods to integrate uncertainty about future weather conditions and model parameters. We use extensive experimental wheat yield data ( n  = 25,841) to learn G×E patterns and validate, using left-trial-out cross-validation, the predictive performance of the model. Subsequently, we use the fitted model to generate circa 143 million grain yield data points for 28 wheat genotypes in 16 locations in France, over 16 years of historical weather records. The phenotypes generated by the simulation platform have multiple downstream uses; we illustrate this by predicting the distribution of expected yield at 448 cultivar-location combinations and performing means-stability analyses. Predicting crop performance in environments with limited field testing is challenging. Here the authors combine field experimental, DNA sequence, and weather data to predict genotypes’ future performance. They demonstrate the potential of this approach on a large dataset of wheat grain yield.
Regularized selection indices for breeding value prediction using hyper-spectral image data
High-throughput phenotyping (HTP) technologies can produce data on thousands of phenotypes per unit being monitored. These data can be used to breed for economically and environmentally relevant traits (e.g., drought tolerance); however, incorporating high-dimensional phenotypes in genetic analyses and in breeding schemes poses important statistical and computational challenges. To address this problem, we developed regularized selection indices; the methodology integrates techniques commonly used in high-dimensional phenotypic regressions (including penalization and rank-reduction approaches) into the selection index (SI) framework. Using extensive data from CIMMYT’s (International Maize and Wheat Improvement Center) wheat breeding program we show that regularized SIs derived from hyper-spectral data offer consistently higher accuracy for grain yield than those achieved by standard SIs, and by vegetation indices commonly used to predict agronomic traits. Regularized SIs offer an effective approach to leverage HTP data that is routinely generated in agriculture; the methodology can also be used to conduct genetic studies using high-dimensional phenotypes that are often collected in humans and model organisms including body images and whole-genome gene expression profiles.
Prediction of Genetic Values of Quantitative Traits in Plant Breeding Using Pedigree and Molecular Markers
The availability of dense molecular markers has made possible the use of genomic selection (GS) for plant breeding. However, the evaluation of models for GS in real plant populations is very limited. This article evaluates the performance of parametric and semiparametric models for GS using wheat (Triticum aestivum L.) and maize (Zea mays) data in which different traits were measured in several environmental conditions. The findings, based on extensive cross-validations, indicate that models including marker information had higher predictive ability than pedigree-based models. In the wheat data set, and relative to a pedigree model, gains in predictive ability due to inclusion of markers ranged from 7.7 to 35.7%. Correlation between observed and predictive values in the maize data set achieved values up to 0.79. Estimates of marker effects were different across environmental conditions, indicating that genotype × environment interaction is an important component of genetic variability. These results indicate that GS in plant breeding can be an effective strategy for selecting among lines whose phenotypes have yet to be observed.
HaploBlocker: Creation of Subgroup-Specific Haplotype Blocks and Libraries
The concept of haplotype blocks has been shown to be useful in genetics. Fields of application range from the detection of regions under positive selection to statistical methods that make use of dimension reduction... The concept of haplotype blocks has been shown to be useful in genetics. Fields of application range from the detection of regions under positive selection to statistical methods that make use of dimension reduction. We propose a novel approach (“HaploBlocker”) for defining and inferring haplotype blocks that focuses on linkage instead of the commonly used population-wide measures of linkage disequilibrium. We define a haplotype block as a sequence of genetic markers that has a predefined minimum frequency in the population, and only haplotypes with a similar sequence of markers are considered to carry that block, effectively screening a dataset for group-wise identity-by-descent. From these haplotype blocks, we construct a haplotype library that represents a large proportion of genetic variability with a limited number of blocks. Our method is implemented in the associated R-package HaploBlocker, and provides flexibility not only to optimize the structure of the obtained haplotype library for subsequent analyses, but also to handle datasets of different marker density and genetic diversity. By using haplotype blocks instead of single nucleotide polymorphisms (SNPs), local epistatic interactions can be naturally modeled, and the reduced number of parameters enables a wide variety of new methods for further genomic analyses such as genomic prediction and the detection of selection signatures. We illustrate our methodology with a dataset comprising 501 doubled haploid lines in a European maize landrace genotyped at 501,124 SNPs. With the suggested approach, we identified 2991 haplotype blocks with an average length of 2685 SNPs that together represent 94% of the dataset.
Assessing the burden of COVID-19 in developing countries: systematic review, meta-analysis and public policy implications
IntroductionThe infection fatality rate (IFR) of COVID-19 has been carefully measured and analysed in high-income countries, whereas there has been no systematic analysis of age-specific seroprevalence or IFR for developing countries.MethodsWe systematically reviewed the literature to identify all COVID-19 serology studies in developing countries that were conducted using representative samples collected by February 2021. For each of the antibody assays used in these serology studies, we identified data on assay characteristics, including the extent of seroreversion over time. We analysed the serology data using a Bayesian model that incorporates conventional sampling uncertainty as well as uncertainties about assay sensitivity and specificity. We then calculated IFRs using individual case reports or aggregated public health updates, including age-specific estimates whenever feasible.ResultsIn most locations in developing countries, seroprevalence among older adults was similar to that of younger age cohorts, underscoring the limited capacity that these nations have to protect older age groups.Age-specific IFRs were roughly 2 times higher than in high-income countries. The median value of the population IFR was about 0.5%, similar to that of high-income countries, because disparities in healthcare access were roughly offset by differences in population age structure.ConclusionThe burden of COVID-19 is far higher in developing countries than in high-income countries, reflecting a combination of elevated transmission to middle-aged and older adults as well as limited access to adequate healthcare. These results underscore the critical need to ensure medical equity to populations in developing countries through provision of vaccine doses and effective medications.
A Scale-Corrected Comparison of Linkage Disequilibrium Levels between Genic and Non-Genic Regions
The understanding of non-random association between loci, termed linkage disequilibrium (LD), plays a central role in genomic research. Since causal mutations are generally not included in genomic marker data, LD between those and available markers is essential for capturing the effects of causal loci on localizing genes responsible for traits. Thus, the interpretation of association studies requires a detailed knowledge of LD patterns. It is well known that most LD measures depend on minor allele frequencies (MAF) of the considered loci and the magnitude of LD is influenced by the physical distances between loci. In the present study, a procedure to compare the LD structure between genomic regions comprising several markers each is suggested. The approach accounts for different scaling factors, namely the distribution of MAF, the distribution of pair-wise differences in MAF, and the physical extent of compared regions, reflected by the distribution of pair-wise physical distances. In the first step, genomic regions are matched based on similarity in these scaling factors. In the second step, chromosome- and genome-wide significance tests for differences in medians of LD measures in each pair are performed. The proposed framework was applied to test the hypothesis that the average LD is different in genic and non-genic regions. This was tested with a genome-wide approach with data sets for humans (Homo sapiens), a highly selected chicken line (Gallus gallus domesticus) and the model plant Arabidopsis thaliana. In all three data sets we found a significantly higher level of LD in genic regions compared to non-genic regions. About 31% more LD was detected genome-wide in genic compared to non-genic regions in Arabidopsis thaliana, followed by 13.6% in human and 6% chicken. Chromosome-wide comparison discovered significant differences on all 5 chromosomes in Arabidopsis thaliana and on one third of the human and of the chicken chromosomes.
Factors Affecting the Accuracy of Genotype Imputation in Populations from Several Maize Breeding Programs
Genomic selection and association mapping offer great potential to increase rates of genetic progress in plants. The prediction of genomic breeding values usually requires that missing genotypes be imputed because a proportion of genotypes is usually uncalled by the genotyping algorithm, different individuals may be genotyped using different platforms, or low cost genotyping strategies can involve genotyping some individuals at high density and others at low density. The objective of this paper was to quantify the accuracy of imputation in a maize (Zea mays L.) data set and explore some of the factors that affect it. The factors studied were the density of the low-density platform, level of linkage disequilibrium, minor allele frequency of the marker being imputed, and degree of genetic relationship between the line being imputed and the training population. The accuracy of imputation was high even when only 8774 genotypes constitute the low-density platform. The correlation between the true and imputed genotypes was 0.87. However, there was a dramatic reduction in the accuracy of imputation when the low-density platforms had fewer than 8774 genotypes. Genetic relatedness between an individual having its genotypes imputed and the individuals genotyped with the high-density platform was important. The design of an information nucleus that incorporates imputation for the purposes of implementing genomic selection and association mapping in small independent breeding programs was discussed.
Genomic Prediction of Genotype × Environment Interaction Kernel Regression Models
In genomic selection (GS), genotype × environment interaction (G × E) can be modeled by a marker × environment interaction (M × E). The G × E may be modeled through a linear kernel or a nonlinear (Gaussian) kernel. In this study, we propose using two nonlinear Gaussian kernels: the reproducing kernel Hilbert space with kernel averaging (RKHS KA) and the Gaussian kernel with the bandwidth estimated through an empirical Bayesian method (RKHS EB). We performed single‐environment analyses and extended to account for G × E interaction (GBLUP‐G × E, RKHS KA‐G × E and RKHS EB‐G × E) in wheat (Triticum aestivum L.) and maize (Zea mays L.) data sets. For single‐environment analyses of wheat and maize data sets, RKHS EB and RKHS KA had higher prediction accuracy than GBLUP for all environments. For the wheat data, the RKHS KA‐G × E and RKHS EB‐G × E models did show up to 60 to 68% superiority over the corresponding single environment for pairs of environments with positive correlations. For the wheat data set, the models with Gaussian kernels had accuracies up to 17% higher than that of GBLUP‐G × E. For the maize data set, the prediction accuracy of RKHS EB‐G × E and RKHS KA‐G × E was, on average, 5 to 6% higher than that of GBLUP‐G × E. The superiority of the Gaussian kernel models over the linear kernel is due to more flexible kernels that accounts for small, more complex marker main effects and marker‐specific interaction effects.
Genomic Heritability: What Is It?
Whole-genome regression methods are being increasingly used for the analysis and prediction of complex traits and diseases. In human genetics, these methods are commonly used for inferences about genetic parameters, such as the amount of genetic variance among individuals or the proportion of phenotypic variance that can be explained by regression on molecular markers. This is so even though some of the assumptions commonly adopted for data analysis are at odds with important quantitative genetic concepts. In this article we develop theory that leads to a precise definition of parameters arising in high dimensional genomic regressions; we focus on the so-called genomic heritability: the proportion of variance of a trait that can be explained (in the population) by a linear regression on a set of markers. We propose a definition of this parameter that is framed within the classical quantitative genetics theory and show that the genomic heritability and the trait heritability parameters are equal only when all causal variants are typed. Further, we discuss how the genomic variance and genomic heritability, defined as quantitative genetic parameters, relate to parameters of statistical models commonly used for inferences, and indicate potential inferential problems that are assessed further using simulations. When a large proportion of the markers used in the analysis are in LE with QTL the likelihood function can be misspecified. This can induce a sizable finite-sample bias and, possibly, lack of consistency of likelihood (or Bayesian) estimates. This situation can be encountered if the individuals in the sample are distantly related and linkage disequilibrium spans over short regions. This bias does not negate the use of whole-genome regression models as predictive machines; however, our results indicate that caution is needed when using marker-based regressions for inferences about population parameters such as the genomic heritability.