Crop growth models for the -omics era: the EU-SPICY project

The prediction of phenotypic responses from genetic and environmental information is an area of active research in genetics, physiology and statistics. Rapidly increasing amounts of phenotypic information become available as a consequence of high throughput phenotyping techniques, while more and cheaper genotypic data follow from the development of new genotyping platforms. , A wide array of -omics data can be generated linking genotype and phenotype. Continuous monitoring of environmental conditions has become an accessible option. This wealth of data requires a drastic rethinking of the traditional quantitative genetic approach to modeling phenotypic variation in terms of genetic and environmental differences. Where in the past a single phenotypic trait was partitioned in a genetic and environmental component by analysis of variance techniques, nowadays we desire to model multiple, interrelated and often time dependent, phenotypic traits as a function of genes (QTLs) and environmental inputs, while we would like to include transcription information as well. The EU project 'Smart tools for Prediction and Improvement of Crop Yield' (KBBE-2008-211347), or SPICY, aims at the development of genotype-to-phenotype models that fully integrate genetic, genomic, physiological and environmental information to achieve accurate phenotypic predictions across a wide variety of genetic and environmental configurations. Pepper (Capsicum annuum) is chosen as the model crop, because of the availability of genetically characterized populations and of generic models for continuous crop growth and greenhouse production. In the presentation the objectives and structure of SPICY as well as its philosophy will be discussed

QTLMAS 2009: simulated dataset

Background - The simulation of the data for the QTLMAS 2009 Workshop is described. Objective was to simulate observations from a growth curve which was influenced by a number of QTL. Results - The data consisted of markers, phenotypes and pedigree. Genotypes of 453 markers, distributed over 5 chromosomes of 1 Morgan each, were simulated for 2,025 individuals. From those, 25 individuals were parents of the other 2,000 individuals. The 25 parents were genetically related. Phenotypes were simulated according to a logistic growth curve and were made available for 1,000 of the 2,000 offspring individuals. The logistic growth curve was specified by three parameters. Each parameter was influenced by six Quantitative Trait Loci (QTL), positioned at the five chromosomes. For each parameter, one QTL had a large effect and five QTL had small effects. Variance of large QTL was five times the variance of small QTL. Simulated data was made available at http://www.qtlmas2009.wur.nl/UK/Dataset

Intracranial EEG fluctuates over months after implanting electrodes in human brain.

OBJECTIVE: Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings. APPROACH: Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for the duration of each patient\u27s recording. Metrics to capture post-implantation feature changes and inflexion points were computed on group and individual levels. A linear mixed model was used to characterize transient group-level changes in feature values post-implantation and independent linear models were used to describe individual variability. MAIN RESULTS: A significant decline in features important to seizure detection and prediction algorithms (mean line length, energy, and half-wave), as well as mean power in the Berger and high gamma bands, was observed in many patients over 100 d following implantation. In addition, spatial variability across electrodes declines post-implantation following a similar timeframe. All selected features decreased by 14-50% in the initial 75 d of recording on the group level, and at least one feature demonstrated this pattern in 13 of the 15 patients. Our findings indicate that iEEG signal features demonstrate increased variability following implantation, most notably in the weeks immediately post-implant. SIGNIFICANCE: These findings suggest that conclusions drawn from iEEG, both clinically and for research, should account for spatiotemporal signal variability and that properly assessing the iEEG in patients, depending upon the application, may require extended monitoring

Comparison of analyses of the QTLMAS XIII common dataset. I: genomic selection

Background - Genomic selection, the use of markers across the whole genome, receives increasing amounts of attention and is having more and more impact on breeding programs. Development of statistical and computational methods to estimate breeding values based on markers is a very active area of research. A simulated dataset was analyzed by participants of the QTLMAS XIII workshop, allowing a comparison of the ability of different methods to estimate genomic breeding values. Methods - A best case scenario was analyzed by the organizers where QTL genotypes were known. Participants submitted estimated breeding values for 1000 unphenotyped individuals together with a description of the applied method(s). The submitted breeding values were evaluated for correlation with the simulated values (accuracy), rank correlation of the best 10% of individuals and error in predictions. Bias was tested by regression of simulated on estimated breeding values. Results - The accuracy obtained from the best case scenario was 0.94. Six research groups submitted 19 sets of estimated breeding values. Methods that assumed the same variance for markers showed accuracies, measured as correlations between estimated and simulated values, ranging from 0.75 to 0.89 and rank correlations between 0.58 and 0.70. Methods that allowed different marker variances showed accuracies ranging from 0.86 to 0.94 and rank correlations between 0.69 and 0.82. Methods assuming equal marker variances were generally more biased and showed larger prediction errors. Conclusions - The best performing methods achieved very high accuracies, close to accuracies achieved in a best case scenario where QTL genotypes were known without error. Methods that allowed different marker variances generally outperformed methods that assumed equal marker variances. Genomic selection methods performed well compared to traditional, pedigree only, methods; all methods showed higher accuracies than those obtained for breeding values estimated solely on pedigree relationship

Adding gene transcripts into genomic prediction improves accuracy and reveals sampling time dependence.

Recent developments allowed generating multiple high-quality \u27omics\u27 data that could increase the predictive performance of genomic prediction for phenotypes and genetic merit in animals and plants. Here, we have assessed the performance of parametric and nonparametric models that leverage transcriptomics in genomic prediction for 13 complex traits recorded in 478 animals from an outbred mouse population. Parametric models were implemented using the best linear unbiased prediction, while nonparametric models were implemented using the gradient boosting machine algorithm. We also propose a new model named GTCBLUP that aims to remove between-omics-layer covariance from predictors, whereas its counterpart GTBLUP does not do that. While gradient boosting machine models captured more phenotypic variation, their predictive performance did not exceed the best linear unbiased prediction models for most traits. Models leveraging gene transcripts captured higher proportions of the phenotypic variance for almost all traits when these were measured closer to the moment of measuring gene transcripts in the liver. In most cases, the combination of layers was not able to outperform the best single-omics models to predict phenotypes. Using only gene transcripts, the gradient boosting machine model was able to outperform best linear unbiased prediction for most traits except body weight, but the same pattern was not observed when using both single nucleotide polymorphism genotypes and gene transcripts. Although the GTCBLUP model was not able to produce the most accurate phenotypic predictions, it showed the highest accuracies for breeding values for 9 out of 13 traits. We recommend using the GTBLUP model for prediction of phenotypes and using the GTCBLUP for prediction of breeding values

Prediction performance of linear models and gradient boosting machine on complex phenotypes in outbred mice.

We compared the performance of linear (GBLUP, BayesB, and elastic net) methods to a nonparametric tree-based ensemble (gradient boosting machine) method for genomic prediction of complex traits in mice. The dataset used contained genotypes for 50,112 SNP markers and phenotypes for 835 animals from 6 generations. Traits analyzed were bone mineral density, body weight at 10, 15, and 20 weeks, fat percentage, circulating cholesterol, glucose, insulin, triglycerides, and urine creatinine. The youngest generation was used as a validation subset, and predictions were based on all older generations. Model performance was evaluated by comparing predictions for animals in the validation subset against their adjusted phenotypes. Linear models outperformed gradient boosting machine for 7 out of 10 traits. For bone mineral density, cholesterol, and glucose, the gradient boosting machine model showed better prediction accuracy and lower relative root mean squared error than the linear models. Interestingly, for these 3 traits, there is evidence of a relevant portion of phenotypic variance being explained by epistatic effects. Using a subset of top markers selected from a gradient boosting machine model helped for some of the traits to improve the accuracy of prediction when these were fitted into linear and gradient boosting machine models. Our results indicate that gradient boosting machine is more strongly affected by data size and decreased connectedness between reference and validation sets than the linear models. Although the linear models outperformed gradient boosting machine for the polygenic traits, our results suggest that gradient boosting machine is a competitive method to predict complex traits with assumed epistatic effects

Synchronisation of egg hatching of brown hairstreak (Thecla betulae) and budburst of blackthorn (Prunus spinosa) in a warmer future

Synchronisation of the phenology of insect herbivores and their larval food plant is essential for the herbivores’ fitness. The monophagous brown hairstreak (Thecla betulae) lays its eggs during summer, hibernates as an egg, and hatches in April or May in the Netherlands. Its main larval food plant blackthorn (Prunus spinosa) flowers in early spring, just before the leaves appear. As soon as the Blackthorn opens its buds, and this varies with spring temperatures, food becomes available for the brown hairstreak. However, the suitability of the leaves as food for the young caterpillars is expected to decrease rapidly. Therefore, the timing of egg hatch is an important factor for larval growth. This study evaluates food availability for brown hairstreak at different temperatures. Egg hatch and budburst were monitored from 2004 to 2008 at different sites in the Netherlands. Results showed ample food availability at all monitored temperatures and sites but the degree of synchrony varied strongly with spring temperatures. To further study the effect of temperature on synchronisation, an experiment using normal temperatures of a reference year (T) and temperatures of T + 5°C was carried out in climate chambers. At T + 5°C, both budburst and egg hatch took place about 20 days earlier and thus, on average, elevated temperature did not affect synchrony. However, the total period of budburst was 11 days longer, whereas the period of egg hatching was 3 days shorter. The implications for larval growth by the brown hairstreak under a warmer climate are considered.