Multiparameter persistent homology landscapes identify immune cell spatial patterns in tumors
Cette étude présente une méthode mathématique permettant d'analyser l'organisation spatiale et la densité des cellules immunitaires ayant infiltré des tumeurs
Quantifying and comparing complex spatial biological datasets is crucial for medical applications and remains an active area of research. As datasets become more heterogeneous and complicated, so must the methods that are used to understand them. Multiparameter topology is built upon the assumption that the shape of data depends on multiple parameters, such as scale, outliers, or other parameters (e.g., cell density and oxygen levels in the case of tumors). A key difficulty encountered in multiparameter persistent homology (MPH) is interpreting and comparing data. The present work uses statistical MPH landscapes to overcome this difficulty and quantifies differences in synthetic data of immune cell infiltration as well as clinical tumor histology data of T cells, macrophages, and hypoxia. Highly resolved spatial data of complex systems encode rich and nonlinear information. Quantification of heterogeneous and noisy data—often with outliers, artifacts, and mislabeled points—such as those from tissues, remains a challenge. The mathematical field that extracts information from the shape of data, topological data analysis (TDA), has expanded its capability for analyzing real-world datasets in recent years by extending theory, statistics, and computation. An extension to the standard theory to handle heterogeneous data is multiparameter persistent homology (MPH). Here we provide an application of MPH landscapes, a statistical tool with theoretical underpinnings. MPH landscapes, computed for (noisy) data from agent-based model simulations of immune cells infiltrating into a spheroid, are shown to surpass existing spatial statistics and one-parameter persistent homology. We then apply MPH landscapes to study immune cell location in digital histology images from head and neck cancer. We quantify intratumoral immune cells and find that infiltrating regulatory T cells have more prominent voids in their spatial patterns than macrophages. Finally, we consider how TDA can integrate and interrogate data of different types and scales, e.g., immune cell locations and regions with differing levels of oxygenation. This work highlights the power of MPH landscapes for quantifying, characterizing, and comparing features within the tumor microenvironment in synthetic and real datasets.Anonymized point cloud data have been deposited in GitHub (https://github.com/MultiparameterTDAHistology/SpatialPatterningOfImmuneCells).
Proceedings of the National Academy of Sciences , article en libre accès, 2020