State-of-the art experimental data promises exquisite insight into the spatial heterogeneity in tissue samples. However, the high level of detail in such data is contrasted with a lack of methods that allow an analysis that fully exploits the available spatial information. Persistent Homology (PH) has been very successfully applied to many biological datasets, but it is typically limited to the analysis of single species data. In the first part of my talk, I will highlight two novel techniques in relational PH that we develop to encode spatial heterogeneity of multi species data. Our approaches are based on Dowker complexes and Witness complexes. We apply the methods to synthetic images generated by an agent-based model of tumour-immune cell interactions. We demonstrate that relational PH features can extract biological insight, including the dominant immune cell phenotype (an important predictor of patient prognosis) and the parameter regimes of a data-generating model. I will present an extension to our pipeline which combines graph neural networks (GNN) with local relational PH and significantly enhances the performance of the GNN on the synthetic data. In the second part of the talk, I will showcase a noise-robust extension of Reani and Bobrowski’s cycle registration algorithm (2023) to reconstruct 3D brain atlases of Drosophila flies from a sequence of μ-CT images.