Borozan, Bartol and Prusina, Tomislav and Borozan, Luka and Severdija, Domagoj and Rojas Ringeling, Francisca and Matijevic, Domagoj and Canzar, Stefan (2025) Optimal marker genes for c-separated cell types with SepSolve. GENOME RESEARCH, 35 (12). pp. 2770-2780. ISSN 1088-9051, 1549-5469
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The identification of cell types in single-cell RNA-seq studies relies on the distinct expression signature of marker genes. A small set of target genes is also needed to design probes for targeted spatial transcriptomic experiments and to target proteins in single-cell spatial proteomics or for cell sorting. Although traditional approaches have relied on testing one gene at a time for differential expression between a given cell type and the rest, more recent methods have highlighted the benefits of a joint selection of markers that together distinguish all pairs of cell types simultaneously. However, existing methods either consider all pairs of individual cells, which becomes intractable even for medium-sized data sets, or ignore intra-cell-type expression variation entirely by collapsing all cells of a given type to a single representative. Here, we address these limitations and propose to find a small set of genes such that cell types are c-separated in the selected dimensions, a notion introduced previously in learning a mixture of Gaussians. To this end, we formulate a linear program that naturally takes into account expression variation within cell types without including each pair of individual cells in the model, leading to a highly stable set of marker genes that allow to accurately discriminate between cell types and that can be computed to optimality efficiently.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SELECTION |
| Subjects: | 000 Computer science, information & general works > 004 Computer science 500 Science > 570 Life sciences |
| Divisions: | Informatics and Data Science > Department Computational Life Science > Algorithmische Bioinformatik (Prof. Dr. Stefan Canzar) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Oct 2026 06:25 |
| Last Modified: | 01 Oct 2026 06:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66450 |
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