High order expression dependencies finely resolve cryptic states and subtypes in single cell data

Abel Jansma, Yuelin Yao, Jareth Wolfe, Luigi Del Debbio, Sjoerd Viktor Beentjes, Chris P Ponting*, Ava Khamseh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Single cells are typically typed by clustering into discrete locations in reduced dimensional
transcriptome space. Here we introduce Stator, a data-driven method that identifies cell
(sub)types and states without relying on cells’ local proximity in transcriptome space. Stator labels the same single cell multiply, not just by type and sub-type, but also by state such as activation, maturity or cell cycle sub-phase, through deriving higher-order gene expression dependencies from a sparse gene-by-cell expression matrix. Stator’s finer resolution is clear from analyses of mouse embryonic brain, and human healthy or diseased liver. Rather than only coarse-scale labels of cell type, Stator further resolves cell types into subtypes, and these subtypes into stages of maturity and/or cell cycle phases, and yet further into portions of these phases. Among cryptically homogeneous embryonic cells, for example, Stator finds 34 distinct radial glia states whose gene expression forecasts their future GABAergic or glutamatergic neuronal fate. Further, Stator’s fine resolution of liver cancer states reveals expression programmes that predict patient survival. We provide Stator as a Nextflow pipeline and ShinyApp.
Original languageEnglish
JournalMolecular Systems Biology
DOIs
Publication statusPublished - 2 Jan 2025

Keywords / Materials (for Non-textual outputs)

  • higher-order gene expression dependencies, single-cell transcriptomics, structure learning, cell state, cell cycle phases

Fingerprint

Dive into the research topics of 'High order expression dependencies finely resolve cryptic states and subtypes in single cell data'. Together they form a unique fingerprint.

Cite this