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A fast and efficient approach for genomic selection with high-density markers.

ABSTRACT: Recent advances in high-throughput genotyping have motivated genomic selection using high-density markers. However, an increasingly large number of markers brings up both statistical and computational issues and makes it difficult to estimate the breeding values. We propose to apply the penalized orthogonal-components regression (POCRE) method to estimate breeding values. As a supervised dimension reduction method, POCRE sequentially constructs linear combinations of markers, i.e. orthogonal components, such that these components are most closely correlated to the phenotype. Such a dimension reduction is able to group highly correlated predictors and allows for collinear or nearly collinear markers. Different from BayesB, which predetermines hyperparameters, POCRE uses an empirical Bayes thresholding method to obtain data-driven optimal hyperparameters and effectively select important markers when constructing each component. Demonstrated through simulation studies, POCRE greatly reduces the computing time compared with BayesB. On the other hand, unlike fBayesB which slightly sacrifices prediction accuracy for fast computation, POCRE provides similar or even better accuracy of predicting breeding values than BayesB in both simulation studies and real data analyses.

SUBMITTER: Pungpapong V

PROVIDER: S-EPMC3464110 | biostudies-other | 2012 Oct

REPOSITORIES: biostudies-other

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A fast and efficient approach for genomic selection with high-density markers.

Pungpapong Vitara V Muir William M WM Li Xianran X Zhang Dabao D Zhang Min M

G3 (Bethesda, Md.) 20121001 10

Recent advances in high-throughput genotyping have motivated genomic selection using high-density markers. However, an increasingly large number of markers brings up both statistical and computational issues and makes it difficult to estimate the breeding values. We propose to apply the penalized orthogonal-components regression (POCRE) method to estimate breeding values. As a supervised dimension reduction method, POCRE sequentially constructs linear combinations of markers, i.e. orthogonal com ...[more]

PMID: 23050228

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Project description:BACKGROUND:The availability of high-density (HD) marker panels, genome wide variants and sequence data creates an unprecedented opportunity to dissect the genetic basis of complex traits, enhance genomic selection (GS) and identify causal variants of disease. The disproportional increase in the number of parameters in the genetic association model compared to the number of phenotypes has led to further deterioration in statistical power and an increase in co-linearity and false positive rates. At best, HD panels do not significantly improve GS accuracy and, at worst, reduce accuracy. This is true for both regression and variance component approaches. To remedy this situation, some form of single nucleotide polymorphisms (SNP) filtering or external information is needed. Current methods for prioritizing SNP markers (i.e. BayesB, BayesCπ) are sensitive to the increased co-linearity in HD panels which could limit their performance. RESULTS:In this study, the usefulness of FST, a measure of allele frequency variation among populations, as an external source of information in GS was evaluated. A simulation was carried out for a trait with heritability of 0.4. Data was divided into three subpopulations based on phenotype distribution (bottom 5%, middle 90%, top 5%). Marker data were simulated to mimic a 770 K and 1.5 million SNP marker panel. A ten-chromosome genome with 200 K and 400 K SNPs was simulated. Several scenarios with varying distributions for the quantitative trait loci (QTL) effects were simulated. Using all 200 K markers and no filtering, the accuracy of genomic prediction was 0.77. When marker effects were simulated from a gamma distribution, SNPs pre-selected based on the 99.5, 99.0 and 97.5% quantile of the FST score distribution resulted in an accuracy of 0.725, 0.797, and 0.853, respectively. Similar results were observed under other simulation scenarios. Clearly, the accuracy obtained using all SNPs can be easily achieved using only 0.5 to 1% of all markers. CONCLUSIONS:These results indicate that SNP filtering using already available external information could increase the accuracy of GS. This is especially important as next-generation sequencing technology becomes more affordable and accessible to human, animal and plant applications.

Project description:Since 1959 with the proposal of Double Agar Layer (DAL) method for phage detection and quantification, many sophisticated methods have emerged meanwhile. However, many of them are either too complex/expensive or insensitive to replace routine utilization of DAL method in clinical, environmental and industrial environments. For that purpose, we have explored an alternative method for the detection and quantification of bacteriophages that fulfills the criteria of being rapid, simple and inexpensive. In this paper we have developed a method based on the analysis of optical density kinetics in bacterial cultures exposed to phage-containing samples. Although the decrease in optical density caused by cell lysis was one of the first observable consequences of the effect of viral infection in bacterial cultures, the potential of the method for the assessment of phage abundance has never been fully exploited. In this work we carry out a detailed study of optical density kinetics in phage-infected bacterial cultures, as a function of both, phage abundance and initial concentration of the host organisms. In total, 90 different combinations of bacteria/phage concentrations have been used. The data obtained provide valuable information about sensitivity ranges, duration of the assay, percentages of inhibition and type of lysing behavior for each phage concentration. The method described can detect, as few as 10 phage particles per assay volume after a phage incubation period of 3.5h. The duration of the assay can be shortened to 45min at the expense of losing sensitivity and increasing the limit of detection to 108 pfu/ml. Despite using non-sophisticated technology, the method described has shown sensitivity and response time comparable to other high-end methods. The simplicity of the technology and of the analytical steps involved, make the system susceptible of miniaturization and automation for high-throughput applications which can be implemented in routine analysis in many environments.

Project description:BackgroundArray comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome.ResultsThis paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage.ConclusionPanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.

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A fast and efficient approach for genomic selection with high-density markers.

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A fast and efficient approach for genomic selection with high-density markers.

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