SiFINeT: A clustering-independent method to identify cell-type-specific feature genes and annotate cells

Single-cell sequencing has provided a means of quantifying cellular omic phenotypes. Identifying cell-type-specific feature genes is a crucial aspect of understanding cellular heterogeneity. Over the past decade, many methods have been developed to identify feature genes; however, these methods either depend on dubious clustering results or fail to annotate cell types with the identified feature genes. We develop a novel clustering-independent method, SiFINeT, to utilize the gene co-expression network topology to identify cell-type-specific feature genes. The identified genes can be used to calculate cellular feature scores and annotate cells with discrete cell types or continuous trajectories. SiFINet outperforms state-of-the-art methods in both feature gene identification and cell-type annotation. SiFINeT has successfully identified new markers in many studies, including new feature genes for senescent cells.