CellSIUS provides sensitive and specific detection of rare cell populations from complex single cell RNA-seq data
CellSIUS provides sensitive and specific detection of rare cell populations from complex single cell RNA-seq data
Abstract Comprehensive benchmarking of computational methods for single-cell RNA sequencing (scRNA-seq) analysis is scarce. Using a modular workflow and a large dataset with known cell composition, we benchmarked feature selection and clustering methodologies for scRNA-seq data. Results highlighted a methodology gap for rare cell population identification for which we developed CellSIUS (Cell Subtype Identification from Upregulated gene Sets). CellSIUS outperformed existing approaches, enabled the identification of rare cell populations and, in contrast to other methods, simultaneously revealed transcriptomic signatures indicative of the rare cells’ function. We exemplified the use of our workflow and CellSIUS for the characterization of a human pluripotent cell 3D spheroid differentiation protocol recapitulating deep-layer corticogenesis in vitro. Results revealed lineage bifurcation between Cajal-Retzius cells and layer V/VI neurons as well as rare cell populations that differ by migratory, metabolic, or cell cycle status, including a choroid plexus neuroepithelial subgroup, revealing previously unrecognized complexity in human stem cell-derived cellular populations.
Schuierer Sven、Hartkopf Huyen、Nigsch Florian、Mapa Felipa、Waldt Annick、Roma Guglielmo、Keller Caroline Gubser、Cuttat Rachel、Salick Max R.、Neri Marilisa、Raymond Joe、Kaykas Ajamete、Bilican Bilada、Wegmann Rebekka
Novartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical ResearchNovartis Institutes for Biomedical Research
生物科学研究方法、生物科学研究技术细胞生物学分子生物学
Single-cell RNA sequencingdata analysisrare cell typesclusteringsoftwarebenchmarkinghuman pluripotent stem cellscortical developmentchoroid plexuslineage mapping
Schuierer Sven,Hartkopf Huyen,Nigsch Florian,Mapa Felipa,Waldt Annick,Roma Guglielmo,Keller Caroline Gubser,Cuttat Rachel,Salick Max R.,Neri Marilisa,Raymond Joe,Kaykas Ajamete,Bilican Bilada,Wegmann Rebekka.CellSIUS provides sensitive and specific detection of rare cell populations from complex single cell RNA-seq data[EB/OL].(2025-03-28)[2025-05-07].https://www.biorxiv.org/content/10.1101/514950.点此复制
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