A Deep Learning Approach to Assessing Cell Identity in Stem Cell-Based Embryo Models

Since the generation of embryoid bodies from embryonic stem cells (ESCs), three-dimensional differentiation has been used to mimic developmental processes. To what extent do these in vitro cell types reflect the cells generated by the embryo? We used deep learning (DL) to develop an integrated model of early human development leveraging existing single-cell RNA-seq (scRNA-seq) and using scvi-tools to both integrate and classify cell types. This tool can interrogate in vitro cell types and assign them both identity and provide an entropy score for the reliability of this classification. In this protocol we explain how to use state-of-the-art tools and our associated, publicly available DL models for early embryonic development to explore phenotypes and cell types derived in vitro. Our tools represent an important new resource to interrogate stem cell-based embryo models and the fidelity with which they recapitulate development.