atheana ritchie

Author information Article notes Copyright and License information Disclaimer. The correct variables are shown in bold. First, none of the modeling techniques specifically identify conditional relationships, which are likely to be ubiquitous in meta-dimensional data. The population is divided into demes across a user-defined number of CPUs for parallelization. RJ For the biological dataset analysis, we applied a variable filtering method before modeling to reduce the noise in the dataset.

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Parameter Ritcchie Genetic effect model No main effects; main stheana interaction effects Effect size a 0. The application can run in parallel with multiple populations and uses the Message Passing Interface MPI for communication. Therefore, the significance level that best distinguishes signal from noise for different types of data is difficult to determine.

Supplementary data are available at Bioinformatics online. Full model detection power is the number of times all of the direct effect variables were identified. For most of the genetic effect models, Lasso has highest power to detect the functional variables.

L1 penalized estimation in the Cox proportional hazards model. Ties are broken using the fitness metrics described later in the text. Frase2 Sarah A. The sequencing of the human genome and significant advancements in high-throughput technology allow for exploratory analyses, which have the goal of interrogating variation at different levels of biological regulation Ideker et al.

The resulting coefficient shrinkage allows for the generation of a parsimonious prediction model.


Fitness is the R 2 value of the model in the testing set. The full model specific detection power was calculated as the number of times both SNPs were identified in the top two variables as determined by the absolute value of the regression coefficient.

For each model, the average fitness balanced accuracyaverage model size number of variables in the best model and various detection powers are shown. This could be a factor in one of the ritvhie criticisms of GWAS—much of the trait variability estimated to be due to genetic factors remains unexplained by the thousands of novel variants identified by these studies Visscher et al.

Data simulation software for whole-genome association and other studies in human genetics.

Atheana Ritchie

Several genetic models were simulated with different effect types, effect sizes and variable counts for a total of 12 models. The overall goal of ATHENA is to provide the user with a platform to flexibly apply the statistical techniques to identify models that may be missed by other methods or any single method alone.

There is no direct correlation between the RJ importance scores and a more interpretable metric such as a P -value.

The filtering-modeling pipeline used here does have certain limitations. Specifically, we used a modified version of the importance score, which takes into account correlated predictor variable i.

Published by Oxford University Press. This could be, in part, due to the manner in which the meta-dimensional data were simulated. Although genome-wide association studies have identified many novel variants associated with hundreds of traits, a large proportion of the estimated trait heritability remains unexplained.

Training begins by generating a random population of binary strings initialized to be functional ANNs or SRs. EV detection power is the number of times the EV was identified in the best model. Detection power is defined as the number of times out of datasets the indicated variable s is identified.


For example, multifactor dimensionality reduction performs an exhaustive analysis of all n-wise interacting loci to generate multilocus predictor models Ritchie et al. Five years of GWAS discovery. For this analysis, fitness is calculated using R 2 for quantitative outcomes, where, for each individual i, y is the observed value, y-hat is the predicted value and y-bar is the mean of the observed values Equation 1.

ANNs are a collection of analog processors that operate in parallel to model the relationship between a set of input variables i. The solutions with the highest fitness are selected for crossover and reproduction, and a new population is generated.

ATHENA: the analysis tool for heritable and environmental network associations

The penetrance functions used to generate the models can be found in Supplementary Table S1. Although they contain many of the same variables, the testing R 2 is substantially greater when the number of variables is reduced in Step 3. For example, genome-wide association studies GWAS calculate the association of each individual single nucleotide polymorphism SNP from a high-throughput genotyping platform with the trait of interest.

If the correlation patterns between the discovery and replication datasets are different, the effect sizes and significance levels will also be different, making exact replication difficult. The P -value is then corrected for all of the statistical tests that were done Watanabe,