Lineage-informed factor analysis reveals heritable programs of single-cell gene expression

Staklinski, Stephen J, Siepel, Adam (September 2026) Lineage-informed factor analysis reveals heritable programs of single-cell gene expression. bioRxiv. ISSN 2692-8205 (Submitted)

PDF 10.64898.2026.09.21.753290.pdf - Submitted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (13MB)

Abstract

Single-cell transcriptomics has transformed our ability to characterize cellular identity, but present-day gene expression profiles capture only a snapshot of a process that unfolds across cell division history. Recent single-cell lineage-tracing technologies make it possible to reconstruct cell division histories for thousands of cells, opening a window into how gene expression evolves. Yet observed gene expression is often redundant, with correlations among genes reflecting underlying latent biological programs and regulatory networks. To capture this structure, we introduce scPFA, a single-cell phylogenetic factor analysis framework that represents gene expression through a small set of latent factors that evolve along lineages under a phylogenetic prior, capturing correlated structure hidden in present-day observations alone. Simulations demonstrate accurate recovery of latent factors and covariance structure across conditions. Applied to developmental and cancer lineage-tracing datasets, the model uncovers biologically interpretable, lineage-associated expression programs. Together, these results demonstrate how lineage-informed factor analysis can reveal temporal biological structure hidden within high-dimensional single-cell data.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > quantitative biology
CSHL Authors:	Siepel, Adam Staklinski, Stephen
Communities:	CSHL labs > Siepel lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	23 September 2026
Date Deposited:	02 Oct 2026 15:47
Last Modified:	02 Oct 2026 15:47
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42333

Actions (login required)

Administrator's edit/view item