A supervised graph-based deep learning algorithm to detect and quantify clustered particles

Considerable efforts are currently being devoted to characterizing the topography of membrane-embedded proteins using combinations of biophysical and numerical analytical approaches. In this work, we present an end-to-end (i.e., human intervention-independent) algorithm consisting of two concatenated binary Graph Neural Network (GNNs) classifiers with the aim of detecting and quantifying dynamic clustering of particles. As the algorithm only needs simulated data to train the GNNs, it is parameter-independent. The GNN-based algorithm is first tested on datasets based on simulated, albeit biologically realistic data, and validated on actual fluorescence microscopy experimental data. Application of the new GNN method is shown to be faster than other currently used approaches for high-dimensional SMLM datasets, with the additional advantage that it can be implemented on standard desktop computers. Furthermore, GNN models obtained via training procedures are reusable. To the best of our knowledge, this is the first application of GNN-based approaches to the analysis of particle aggregation, with potential applications to the study of nanoscopic particles like the nanoclusters of membrane-associated proteins in live cells.