LOCATOR: feature extraction and spatial analysis of the cancer tissue microenvironment using mass cytometry imaging technologies

Abstract

Motivation

Recent advances in highly multiplexed imaging have provided unprecedented insights into the complex cellular organization of tissues, with many applications in translational medicine. However, downstream analyses of multiplexed imaging data face several technical limitations, and although some computational methods and bioinformatics tools are available, deciphering the complex spatial organization of cellular ecosystems remains a challenging problem. Results

To mitigate this problem, we develop a novel computational tool, LOCATOR (anaLysis Of CAncer Tissue micrOenviRonment), for spatial analysis of cancer tissue microenvironments using data acquired from mass cytometry imaging technologies. LOCATOR introduces a graph-based representation of tissue images to describe features of the cellular organization and deploys downstream analysis and visualization utilities that can be used for data-driven patient-risk stratification. Our case studies using mass cytometry imaging data from two well-annotated breast cancer cohorts re-confirmed that the spatial organization of the tumour-immune microenvironment is strongly associated with the clinical outcome in breast cancer. In addition, we report interesting potential associations between the spatial organization of macrophages and patients’ survival. Our work introduces an automated and versatile analysis tool for mass cytometry imaging data with many applications in future cancer research projects.