SCHiRM: Single Cell Hierarchical Regression Model to detect dependencies in read count data

MotivationModern single cell RNA sequencing (scRNA-seq) technologies have made it possible to measure the RNA content of individual cells. The scRNA-seq data provide us with detailed information about the cellular states but, despite several pioneering efforts, it remains an open research question how regulatory networks could be inferred from these noisy discrete read count data.\n\nResultsHere, we introduce a hierarchical regression model which is designed for detecting dependencies in scRNA-seq and other count data. We model count data using the Poisson-log normal distribution and, by means of our hierarchical formulation, detect the dependencies between genes using linear regression model for the latent, cell-specific gene expression rate parameters. The hierarchical formulation allows us to model count data without artificial data transformations and makes it possible to incorporate normalization information directly into the latent layer of the model. We test the proposed approach using both simulated and experimental data. Our results show that the proposed approach performs better than standard regression techniques in parameter inference task as well as in variable selection task.\n\nAvailabilityAn implementation of the method is available at https://github.com/jeintos/SCHiRM.\n\nContactjukka.intosalmi@aalto.fi, harri.lahdesmaki@aalto.fi