18,247 research outputs found
Genomic selection in rubber tree breeding: A comparison of models and methods for managing G×E interactions
Several genomic prediction models combining genotype × environment (G×E) interactions have recently been developed and used for genomic selection (GS) in plant breeding programs. G×E interactions reduce selection accuracy and limit genetic gains in plant breeding. Two data sets were used to compare the prediction abilities of multienvironment G×E genomic models and two kernel methods. Specifically, a linear kernel, or GB (genomic best linear unbiased predictor [GBLUP]), and a nonlinear kernel, or Gaussian kernel (GK), were used to compare the prediction accuracies (PAs) of four genomic prediction models: 1) a single-environment, main genotypic effect model (SM); 2) a multienvironment, main genotypic effect model (MM); 3) a multienvironment, single-variance G×E deviation model (MDs); and 4) a multienvironment, environment-specific variance G×E deviation model (MDe). We evaluated the utility of genomic selection (GS) for 435 individual rubber trees at two sites and genotyped the individuals via genotyping-by-sequencing (GBS) of single-nucleotide polymorphisms (SNPs). Prediction models were used to estimate stem circumference (SC) during the first 4 years of tree development in conjunction with a broad-sense heritability (H2) of 0.60. Applying the model (SM, MM, MDs, and MDe) and kernel method (GB and GK) combinations to the rubber tree data revealed that the multienvironment models were superior to the single-environment genomic models, regardless of the kernel (GB or GK) used, suggesting that introducing interactions between markers and environmental conditions increases the proportion of variance explained by the model and, more importantly, the PA. Compared with the classic breeding method (CBM), methods in which GS is incorporated resulted in a 5-fold increase in response to selection for SC with multienvironment GS (MM, MDe, or MDs). Furthermore, GS resulted in a more balanced selection response for SC and contributed to a reduction in selection time when used in conjunction with traditional genetic breeding programs. Given the rapid advances in genotyping methods and their declining costs and given the overall costs of large-scale progeny testing and shortened breeding cycles, we expect GS to be implemented in rubber tree breeding programs
A Quadratically Regularized Functional Canonical Correlation Analysis for Identifying the Global Structure of Pleiotropy with NGS Data
Investigating the pleiotropic effects of genetic variants can increase
statistical power, provide important information to achieve deep understanding
of the complex genetic structures of disease, and offer powerful tools for
designing effective treatments with fewer side effects. However, the current
multiple phenotype association analysis paradigm lacks breadth (number of
phenotypes and genetic variants jointly analyzed at the same time) and depth
(hierarchical structure of phenotype and genotypes). A key issue for high
dimensional pleiotropic analysis is to effectively extract informative internal
representation and features from high dimensional genotype and phenotype data.
To explore multiple levels of representations of genetic variants, learn their
internal patterns involved in the disease development, and overcome critical
barriers in advancing the development of novel statistical methods and
computational algorithms for genetic pleiotropic analysis, we proposed a new
framework referred to as a quadratically regularized functional CCA (QRFCCA)
for association analysis which combines three approaches: (1) quadratically
regularized matrix factorization, (2) functional data analysis and (3)
canonical correlation analysis (CCA). Large-scale simulations show that the
QRFCCA has a much higher power than that of the nine competing statistics while
retaining the appropriate type 1 errors. To further evaluate performance, the
QRFCCA and nine other statistics are applied to the whole genome sequencing
dataset from the TwinsUK study. We identify a total of 79 genes with rare
variants and 67 genes with common variants significantly associated with the 46
traits using QRFCCA. The results show that the QRFCCA substantially outperforms
the nine other statistics.Comment: 64 pages including 12 figure
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
Bayesian Approximate Kernel Regression with Variable Selection
Nonlinear kernel regression models are often used in statistics and machine
learning because they are more accurate than linear models. Variable selection
for kernel regression models is a challenge partly because, unlike the linear
regression setting, there is no clear concept of an effect size for regression
coefficients. In this paper, we propose a novel framework that provides an
effect size analog of each explanatory variable for Bayesian kernel regression
models when the kernel is shift-invariant --- for example, the Gaussian kernel.
We use function analytic properties of shift-invariant reproducing kernel
Hilbert spaces (RKHS) to define a linear vector space that: (i) captures
nonlinear structure, and (ii) can be projected onto the original explanatory
variables. The projection onto the original explanatory variables serves as an
analog of effect sizes. The specific function analytic property we use is that
shift-invariant kernel functions can be approximated via random Fourier bases.
Based on the random Fourier expansion we propose a computationally efficient
class of Bayesian approximate kernel regression (BAKR) models for both
nonlinear regression and binary classification for which one can compute an
analog of effect sizes. We illustrate the utility of BAKR by examining two
important problems in statistical genetics: genomic selection (i.e. phenotypic
prediction) and association mapping (i.e. inference of significant variants or
loci). State-of-the-art methods for genomic selection and association mapping
are based on kernel regression and linear models, respectively. BAKR is the
first method that is competitive in both settings.Comment: 22 pages, 3 figures, 3 tables; theory added; new simulations
presented; references adde
Kernel-based aggregation of marker-level genetic association tests involving copy-number variation
Genetic association tests involving copy-number variants (CNVs) are
complicated by the fact that CNVs span multiple markers at which measurements
are taken. The power of an association test at a single marker is typically
low, and it is desirable to pool information across the markers spanned by the
CNV. However, CNV boundaries are not known in advance, and the best way to
proceed with this pooling is unclear. In this article, we propose a
kernel-based method for aggregation of marker-level tests and explore several
aspects of its implementation. In addition, we explore some of the theoretical
aspects of marker-level test aggregation, proposing a permutation-based
approach that preserves the family-wise error rate of the testing procedure,
while demonstrating that several simpler alternatives fail to do so. The
empirical power of the approach is studied in a number of simulations
constructed from real data involving a pharmacogenomic study of gemcitabine,
and compares favorably with several competing approaches
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