This course focuses on computational methods in cryo-EM, including three-dimensional ab-initio modelling, structure refinement, resolving structural variability of heterogeneous populations, particle picking, model validation, and resolution determination. Special emphasis is given to methods that play a significant role in many other data science applications. These comprise of key elements of statistical inference, image processing, optimization, and dimensionality reduction. The software packages RELION and ASPIRE are routinely used for class demonstration on both simulated and publicly available experimental datasets.