Optimal marker genes for c-separated cell types with SepSolve

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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Abstract

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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