Cell Type and State

For a given cell subset, we typically identified its cell type or state using a combination of methods including examination of differentially expressed genes for a cell subset and scoring cells with gene expression programs curated from existing knowledge. These annotation methods are demonstrated in the tumor toolbox paper and example code is here.

In addition to cell types, we also want to identify cell states or gene expression programs, such as the cytotoxicity program in T cells or the type-I interferon response across multiple immune cell types. To identify cell states or programs, the genes contributing to those programs, and how much each program is expressed in each single cell, we commonly use either non-negative matrix factorization (NMF) or topic modeling. An example of using NMF to identify cell states in COVID-19 lung epithelial cells and fibroblasts is here, and an example of using topic modeling to identify cell states in intestinal immune cells is here.