Wiener-Granger causality is a well-established concept of causality based on stochasticity and the flow of time, with applications in a broad array of quantitative sciences. The majority of methods used to measure Wiener-Granger causality are based on linear premises and hence insensitive to non-linear signals. Other frameworks based on non-parametric techniques are often computationally expensive and susceptible to overfitting or lack of sensitivity.In this thesis, Paper I investigates the application of linear Wiener-Granger causality to migrating cancer cell data obtained using a Systems Microscopy experimental platform. Paper II represents a review of non-parametric measures based on information theory and discusses a number of related bottlenecks and potential routes of circumvention. Paper III studies the properties of a frequently used non-parametric information theoretical measure for a class of non-Gaussian distributions. Paper IV introduces a new efficient scheme for non-parametric analysis of Wiener-Granger causality based on kernel canonical correlations, and studies the connection between this new scheme and the information theoretical approach. Lastly, Paper V draws upon the results in the preceding paper to discuss non-parametric analysis of Wiener-Granger causality in partially observed systems.Altogether, the work presented in this thesis constitutes a comprehensive review on measures of Wiener-Granger causality in general, and in particular, features new insights on efficient non-parametric analysis of Wiener-Granger causality in high-dimensional settings.