GMM-Based Expanded Feature Space as a Way to Extract Useful Information for Rare Cell Subtypes Identification in Single-Cell Mass Cytometry.

Cell subtype identification from mass cytometry data presents a persisting challenge, particularly when dealing with millions of cells. Current solutions are consistently under development, however, their accuracy and sensitivity remain limited, particularly in rare cell-type detection due to frequent downsampling. Additionally, they often lack the capability to analyze large data sets. To overcome these limitations, a new method was suggested to define an extended feature space. When combined with the robust clustering algorithm for big data, it results in more efficient cell clustering. Each marker's intensity distribution is presented as a mixture of normal distributions (Gaussian Mixture Model, GMM), and the expanded space is created by spanning over all obtained GMM components. The projection of the initial flow cytometry marker domain into the expanded space employs GMM-based membership functions. An evaluation conducted on three established cellular identification algorithms (FlowSOM, ClusterX, and PARC) utilizing the most substantial publicly available annotated dataset by Samusik et al. demonstrated the superior performance of the suggested approach in comparison to the standard. Although our approach identified 20 cell clusters instead of the expected 24, their intra-cluster homogeneity and inter-cluster differences were superior to the 24-cluster FlowSOM-based solution.