Implications of avoiding overlap between training and testing data sets when evaluating genomic predictions of genetic merit

The aim of this study was to evaluate and quantify the importance of avoiding overlap between training and testing subsets of data when evaluating the effectiveness of predictions of genetic merit based on genetic markers. Genomic selection holds great potential for increasing the accuracy of selection in young bulls and is likely to lead quickly to more widespread use of these young bulls with a shorter generation interval and faster genetic improvement. Practical implementations of genomic selection in dairy cattle commonly involve results of national genetic evaluations being used as the dependent variable to evaluate the predictive ability of genetic markers. Selection index theory was used to demonstrate how ignoring correlations among errors of prediction between animals in training and testing sets could result in overestimates of accuracy of genomic predictions. Correlations among errors of prediction occur when estimates of genetic merit of training animals used in prediction are taken from the same genetic evaluation as estimates for validation of animals. Selection index theory was used to show a substantial degree of error correlation when animals used for testing genomic predictions are progeny of training animals, when heritability is low, and when the number of recorded progeny for both training and testing animals is low. Even when training involves a dependent variable that is not influenced by the progeny records of testing animals (i.e., historic proofs), error correlations can still result from records of relatives of training animals contributing to both the historic proofs and the predictions of genetic merit of testing animals. A simple simulation was used to show how an error correlation could result in spurious confirmation of predictive ability that was overestimated in the training population because of ascertainment bias. Development of a method of testing genomic selection predictions that allows unbiased testing when training and testing variables are estimated breeding values from the same genetic evaluation would simplify training and testing of genomic predictions. In the meantime, a 4-step approach for separating records used for training from those used for testing after correction of fixed effects is suggested when use of progeny averages of adjusted records (e.g., daughter yield deviations) would result in inefficient use of the information available in the data.</p

Sensitivity analysis in a market with memory

A general market model with memory is considered in terms of stochastic functional differential equations. We aim at representation formulae for the sensitivity analysis of the dependence of option prices on the memory. This implies a generalization of the concept of delta.Comment: Withdrawn by the authors due to an error in equation (2.6). A new work is in preparatio

BlogForever D2.6: Data Extraction Methodology

This report outlines an inquiry into the area of web data extraction, conducted within the context of blog preservation. The report reviews theoretical advances and practical developments for implementing data extraction. The inquiry is extended through an experiment that demonstrates the effectiveness and feasibility of implementing some of the suggested approaches. More specifically, the report discusses an approach based on unsupervised machine learning that employs the RSS feeds and HTML representations of blogs. It outlines the possibilities of extracting semantics available in blogs and demonstrates the benefits of exploiting available standards such as microformats and microdata. The report proceeds to propose a methodology for extracting and processing blog data to further inform the design and development of the BlogForever platform

Calculation of multiple-trait sire reliability for traits included in a dairy cattle fertility index

The advent of genetic evaluations for fertility traits in the UK offers valuable information to farmers that can be used to control fertility problems and safeguard against involuntary culling. In addition to estimated genetic merit, proof reliabilities are required to make correct use of this genetic information. Exact reliabilities, based on the inverse of the coefficient matrix, cannot be estimated for large data sets because of computational restrictions. A method to calculate approximate reliabilities was implemented based on a six-trait sire model. Traits considered were interval between first and second calving, interval between first calving and first service, non-return rate 56 days post first service, number of inseminations per conception, daily milk yield at test nearest day 110 and body condition score. Sire reliabilities were calculated in four steps. Firstly, the number of effective daughters was calculated for each bull, separately for each trait, based on total number of daughters and daughter distribution across herd-year-seasons. Secondly, multiple-trait reliabilities were calculated, based on bull daughter contribution, applying selection index theory on independent daughter groups. Thirdly, (great-) grand-daughter contribution was added to the reliability of each bull, using daughter-based reliability of sons and maternal grandsons. An adjustment was made to account for the probability of bull and son or grandson having daughters in the same herd-year-season. Without the adjustment, reliabilities were inflated by proportionately 0·15 to 0·25. Finally, parent (sire and maternal grandsire) contribution was added to the reliability of each bull. The procedure was first tested on a data subset of 28 061 cow records from 285 bulls. Approximate reliabilities were compared with exact estimates based on the inverse of the coefficient matrix. Mean absolute differences ranged from 0·014 to 0·020 for the six traits and correlation between exact and approximate estimates neared unity. In a full-scale application, sire reliability for the fertility traits increased by proportionately 0·47 to 0·79 over single-trait estimates and the number of bulls with a reliability of 0·60 or more increased by 42 to 115%

Thermodynamic glass transition in a spin glass without time-reversal symmetry

Spin glasses are a longstanding model for the sluggish dynamics that appears at the glass transition. However, spin glasses differ from structural glasses for a crucial feature: they enjoy a time reversal symmetry. This symmetry can be broken by applying an external magnetic field, but embarrassingly little is known about the critical behaviour of a spin glass in a field. In this context, the space dimension is crucial. Simulations are easier to interpret in a large number of dimensions, but one must work below the upper critical dimension (i.e., in d<6) in order for results to have relevance for experiments. Here we show conclusive evidence for the presence of a phase transition in a four-dimensional spin glass in a field. Two ingredients were crucial for this achievement: massive numerical simulations were carried out on the Janus special-purpose computer, and a new and powerful finite-size scaling method.Comment: 10 pages, 6 figure

Genomic selection: the option for new robustness traits?

Genomic selection is rapidly becoming the state-of-the-art genetic selection methodology in dairy cattle breeding schemes around the world. The objective of this paper was to explore possibilities to apply genomic selection for traits related to dairy cow robustness. Deterministic simulations indicate that replacing progeny testing with genomic selection may favour genetic response for production traits at the expense of robustness traits, owing to a disproportional change in accuracies obtained across trait groups. Nevertheless, several options are available to improve the accuracy of genomic selection for robustness traits. Moreover, genomic selection opens up the opportunity to begin selection for new traits using specialised reference populations of limited size where phenotyping of large populations of animals is currently prohibitive. Reference populations for such traits may be nucleus-type herds, research herds or pooled data from (international) research experiments or research herds. The RobustMilk project has set an example for the latter approach, by collating international data for progesterone-based traits, feed intake and energy balance-related traits. Reference population design, both in terms of relatedness of the animals and variability in phenotypic performance, is important to optimise the accuracy of genomic selection. Use of indicator traits, combined with multi-trait genomic prediction models, can further contribute to improved accuracy of genomic prediction for robustness traits. Experience to date indicates that for newly recorded robustness traits that are negatively correlated with the main breeding goal, cow reference populations of =10 000 are required when genotyping is based on medium- or high-density single-nucleotide polymorphism arrays. Further genotyping advances (e.g. sequencing) combined with post-genomics technologies will enhance the opportunities for (genomic) selection to improve cow robustness

An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein

A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen-whose native state is susceptible to the formation of a proto-oligomeric intermediate-we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states

Janus II: a new generation application-driven computer for spin-system simulations

This paper describes the architecture, the development and the implementation of Janus II, a new generation application-driven number cruncher optimized for Monte Carlo simulations of spin systems (mainly spin glasses). This domain of computational physics is a recognized grand challenge of high-performance computing: the resources necessary to study in detail theoretical models that can make contact with experimental data are by far beyond those available using commodity computer systems. On the other hand, several specific features of the associated algorithms suggest that unconventional computer architectures, which can be implemented with available electronics technologies, may lead to order of magnitude increases in performance, reducing to acceptable values on human scales the time needed to carry out simulation campaigns that would take centuries on commercially available machines. Janus II is one such machine, recently developed and commissioned, that builds upon and improves on the successful JANUS machine, which has been used for physics since 2008 and is still in operation today. This paper describes in detail the motivations behind the project, the computational requirements, the architecture and the implementation of this new machine and compares its expected performances with those of currently available commercial systems.Comment: 28 pages, 6 figure

Nature of the spin-glass phase at experimental length scales

We present a massive equilibrium simulation of the three-dimensional Ising spin glass at low temperatures. The Janus special-purpose computer has allowed us to equilibrate, using parallel tempering, L=32 lattices down to T=0.64 Tc. We demonstrate the relevance of equilibrium finite-size simulations to understand experimental non-equilibrium spin glasses in the thermodynamical limit by establishing a time-length dictionary. We conclude that non-equilibrium experiments performed on a time scale of one hour can be matched with equilibrium results on L=110 lattices. A detailed investigation of the probability distribution functions of the spin and link overlap, as well as of their correlation functions, shows that Replica Symmetry Breaking is the appropriate theoretical framework for the physically relevant length scales. Besides, we improve over existing methodologies to ensure equilibration in parallel tempering simulations.Comment: 48 pages, 19 postscript figures, 9 tables. Version accepted for publication in the Journal of Statistical Mechanic

The three dimensional Ising spin glass in an external magnetic field: the role of the silent majority

We perform equilibrium parallel-tempering simulations of the 3D Ising Edwards-Anderson spin glass in a field. A traditional analysis shows no signs of a phase transition. Yet, we encounter dramatic fluctuations in the behaviour of the model: Averages over all the data only describe the behaviour of a small fraction of it. Therefore we develop a new approach to study the equilibrium behaviour of the system, by classifying the measurements as a function of a conditioning variate. We propose a finite-size scaling analysis based on the probability distribution function of the conditioning variate, which may accelerate the convergence to the thermodynamic limit. In this way, we find a non-trivial spectrum of behaviours, where a part of the measurements behaves as the average, while the majority of them shows signs of scale invariance. As a result, we can estimate the temperature interval where the phase transition in a field ought to lie, if it exists. Although this would-be critical regime is unreachable with present resources, the numerical challenge is finally well posed.Comment: 42 pages, 19 figures. Minor changes and added figure (results unchanged