The dissertation presents novel statistically and computationally efficient hypothesis tests for relative similarity and dependency, and precision matrix estimation. The key methodology adopted in this thesis is the class of U-statistic estimators. The class of U-statistics results in a minimum-variance unbiased estimation of a parameter.The first part of the thesis focuses on relative similarity tests applied to the problem of model selection. Probabilistic generative models provide a powerful framework for representing data. Model selection in this generative setting can be challenging. To address this issue, we provide a novel non-parametric hypothesis test of relative similarity and test whether a first candidate model generates a data ...