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PRISM-GEP: Viewing Single-Cell Expression through the Lens of Topic Modeling
Yanir Buznah1, Tal Ishon1, Uri Shaham1
1Bar-Ilan University, Ramat Gan, Israel.
Motivation:
Gene-expression programs (GEPs) are the co-regulated gene modules whose coordinated activity encodes biological processes. Recovering them from single-cell RNA-seq is hard because regulation is many-to-many. A cell can run several programs at once, and a gene can take part in several. Methods that resolve programs along a trajectory break this structure by assigning each gene to a single program.
Results:
PRISM-GEP discovers overlapping gene-expression programs with Latent Dirichlet Allocation, giving it a prior estimated from gene co-expression in place of the flat default it normally assumes. No reference dataset or pathway database is required. Across 15 human and mouse datasets, PRISM-GEP matches specialized factorizations such as cNMF and scHPF on Gene Ontology Biological Process metrics. Over the 43 rankable dataset-by-metric entries its mean rank is level with the best, and unlike every specialized method it never ranks last. The same co-expression geometry orders the genes within each program, recovering developmental cascades on par with GeneTrajectory.
Availability And Implementation:
The implementation of our methods, including all code, datasets, and experimental workflows, is available in Python at https://github.com/shaham-lab/PRISM-GEP. The version used in this paper is archived at https://doi.org/10.5281/zenodo.22659056.
Contact:
Uri Shaham, Bar-Ilan University.
Supplementary Information:
Supplementary data are available at Bioinformatics online.
