Cytocipher determines significantly different populations of cells in single-cell RNA-seq data.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37449901", "kind": "science-record", "revision": 4, "content_hash": "sha256:9c8cf3680cbc46c103a4db23bc573d8d46af685e08df3167d95ff47946760fb6", "created_at": "2026-11-01T19:02:13Z", "updated_at": "2026-11-01T22:09:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Cytocipher determines significantly different populations of cells in single-cell RNA-seq data.", "doi": "10.1093/bioinformatics/btad435", "pmid": "37449901", "authors": ["Brad Balderson", "Michael Piper", "Stefan Thor", "Mikael Bodén"], "journal": "Bioinformatics (Oxford, England)", "year": 2023, "abstract": "MOTIVATION: Identification of cell types using single-cell RNA-seq is revolutionizing the study of multicellular organisms. However, typical single-cell RNA-seq analysis often involves post hoc manual curation to ensure clusters are transcriptionally distinct, which is time-consuming, error-prone, and irreproducible.\nRESULTS: To overcome these obstacles, we developed Cytocipher, a bioinformatics method and scverse compatible software package that statistically determines significant clusters. Application of Cytocipher to normal tissue, development, disease, and large-scale atlas data reveals the broad applicability and power of Cytocipher to generate biological insights in numerous contexts. This included the identification of cell types not previously described in the datasets analysed, such as CD8+ T cell subtypes in human peripheral blood mononuclear cells; cell lineage intermediate states during mouse pancreas development; and subpopulations of luminal epithelial cells over-represented in prostate cancer. Cytocipher also scales to large datasets with high-test performance, as shown by application to the Tabula Sapiens Atlas representing >480 000 cells. Cytocipher is a novel and generalizable method that statistically determines transcriptionally distinct and programmatically reproducible clusters from single-cell data.\nAVAILABILITY AND IMPLEMENTATION: The software version used for this manuscript has been deposited on Zenodo (https://doi.org/10.5281/zenodo.8089546), and is also available via github (https://github.com/BradBalderson/Cytocipher).", "claims": [{"id": "claim-method", "statement": "For a given pair of clusters i and j, two independent Student’s t-tests on enrichment scores determine if they are significantly different (Fig. 1B3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37449901", "locator": "sections[4] \"2.2 Cytocipher cluster-merge\" paragraph 3", "quote": "For a given pair of clusters i and j, two independent Student’s t-tests on enrichment scores determine if they are significantly different (Fig. 1B3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Automatic download of data and reproducible code for the analyses performed are available at https://github.com/BradBalderson/Cytocipher manuscript. Cytocipher is available at https://github.com/BradBalderson/Cytocipher. The software version used for this manuscript has been deposited on Zenodo at https://doi.org/10.5281/zenodo.8089546. The github tutorial includes full code to reproduce the mouse pancreas analysis. All data analysed are publicly available. The E18.5 hypothalamus neuronal subtype data is available in the Gene Expression Omnibus (GEO) database at accession GSE154995 with the cell annotations and UMAP coordinates available in the supplemental data of the original paper (Yaghmaeian Salmani et al. 2022). The E15.5 mouse pancreas data is available in GEO at accession GSE132188 (Bastidas-Ponce et al. 2019). The processed data was downloaded using Scvelo with the scv.datasets.pancreas() function. The human PBMC 3K data are hosted by 10X Genomics, and were downloaded via wget https://cf.10xgenomics.com/samples/cell-exp/1.1.0/pbmc3k/pbmc3k_filtered_gene_bc_matrices.tar.gz. The prostate cancer data was downloaded from http://www.prostatecellatlas.org/ with wget https://cellgeni.cog.sanger.ac.uk/prostatecellatlas/prostate_portal_300921.h5ad. The Tabula Sapiens data is available from figshare https://figshare.com/projects/Tabula_Sapiens/100973 and was downloaded via wget https://figshare.com/ndownloader/files/34702114.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37449901", "locator": "sections[30] \"Data availability\" paragraph 2", "quote": "Automatic download of data and reproducible code for the analyses performed are available at https://github.com/BradBalderson/Cytocipher manuscript. Cytocipher is available at https://github.com/BradBalderson/Cytocipher. The software version used for this manuscript has been deposited on Zenodo at https://doi.org/10.5281/zenodo.8089546. The github tutorial includes full code to reproduce the mouse pancreas analysis. All data analysed are publicly available. The E18.5 hypothalamus neuronal subtype data is available in the Gene Expression Omnibus (GEO) database at accession GSE154995 with the cell annotations and UMAP coordinates available in the supplemental data of the original paper (Yaghmaeian Salmani et al. 2022). The E15.5 mouse pancreas data is available in GEO at accession GSE132188 (Bastidas-Ponce et al. 2019). The processed data was downloaded using Scvelo with the scv.datasets.pancreas() function. The human PBMC 3K data are hosted by 10X Genomics, and were downloaded via wget https://cf.10xgenomics.com/samples/cell-exp/1.1.0/pbmc3k/pbmc3k_filtered_gene_bc_matrices.tar.gz. The prostate cancer data was downloaded from http://www.prostatecellatlas.org/ with wget https://cellgeni.cog.sanger.ac.uk/prostatecellatlas/prostate_portal_300921.h5ad. The Tabula Sapiens data is available from figshare https://figshare.com/projects/Tabula_Sapiens/100973 and was downloaded via wget https://figshare.com/ndownloader/files/34702114."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Cytocipher also scales to large datasets with high-test performance, as shown by application to the Tabula Sapiens Atlas representing >480 000 cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37449901", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Cytocipher also scales to large datasets with high-test performance, as shown by application to the Tabula Sapiens Atlas representing >480 000 cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Cytocipher also scales to large datasets with high-test performance, as shown by application to the Tabula Sapiens Atlas representing >480 000 cells.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37449901"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Cytocipher is available at https://github.com/BradBalderson/Cytocipher. The software version used for this manuscript has been deposited on Zenodo at https://doi.org/10.5281/zenodo.8089546. The github tutorial includes full code to reproduce the mouse pancreas analysis. All data analysed are publicly available. The E18.5 hypothalamus neuronal subtype data is available in the Gene Expression Omnibus (GEO) database at accession GSE154995 with the cell annotations and UMAP coordinates available in the supplemental data of the original paper (Yaghmaeian Salmani et al. 2022). The E15.5 mouse pancreas data is available in GEO at accession GSE132188 (Bastidas-Ponce et al. 2019). The processed data was downloaded using Scvelo with the scv.datasets.pancreas() function. The human PBMC 3K data are hosted by 10X Genomics, and were downloaded via wget https://cf.10xgenomics.com/samples/cell-exp/1.1.0/pbmc3k/pbmc3k_filtered_gene_bc_matrices.tar.gz. The prostate cancer data was downloaded from http://www.prostatecellatlas.org/ with wget https://cellgeni.cog.sanger.ac.uk/prostatecellatlas/prostate_portal_300921.h5ad. The Tabula Sapiens data is available from figshare https://figshare.com/projects/Tabula_Sapiens/100973 and was downloaded via wget https://figshare.com/ndownloader/files/34702114.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Automatic download of data and reproducible code for the analyses performed are available at https://github.com/BradBalderson/Cytocipher manuscript. Cytocipher is available at https://github.com/BradBalderson/Cytocipher. The software version used for this manuscript has been deposited on Zenodo at https://doi.org/10.5281/zenodo.8089546. The github tutorial includes full code to reproduce the mouse pancreas analysis. All data analysed are publicly available. The E18.5 hypothalamus neuronal subtype data is available in the Gene Expression Omnibus (GEO) database at accession GSE154995 with the cell annotations and UMAP coordinates available in the supplemental data of the original paper (Yaghmaeian Salmani et al. 2022). The E15.5 mouse pancreas data is available in GEO at accession GSE132188 (Bastidas-Ponce et al. 2019). The processed data was downloaded using Scvelo with the scv.datasets.pancreas() function. The human PBMC 3K data are hosted by 10X Genomics, and were downloaded via wget https://cf.10xgenomics.com/samples/cell-exp/1.1.0/pbmc3k/pbmc3k_filtered_gene_bc_matrices.tar.gz. The prostate cancer data was downloaded from http://www.prostatecellatlas.org/ with wget https://cellgeni.cog.sanger.ac.uk/prostatecellatlas/prostate_portal_300921.h5ad. 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The prostate cancer data was downloaded from http://www.prostatecellatlas.org/ with wget https://cellgeni.cog.sanger.ac.uk/prostatecellatlas/prostate_portal_300921.h5ad. The Tabula Sapiens data is available from figshare https://figshare.com/projects/Tabula_Sapiens/100973 and was downloaded via wget https://figshare.com/ndownloader/files/34702114.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Automatic download of data and reproducible code for the analyses performed are available at https://github.com/BradBalderson/Cytocipher manuscript. Cytocipher is available at https://github.com/BradBalderson/Cytocipher. The software version used for this manuscript has been deposited on Zenodo at https://doi.org/10.5281/zenodo.8089546. The github tutorial includes full code to reproduce the mouse pancreas analysis. All data analysed are publicly available. The E18.5 hypothalamus neuronal subtype data is available in the Gene Expression Omnibus (GEO) database at accession GSE154995 with the cell annotations and UMAP coordinates available in the supplemental data of the original paper (Yaghmaeian Salmani et al. 2022). The E15.5 mouse pancreas data is available in GEO at accession GSE132188 (Bastidas-Ponce et al. 2019). The processed data was downloaded using Scvelo with the scv.datasets.pancreas() function. The human PBMC 3K data are hosted by 10X Genomics, and were downloaded via wget https://cf.10xgenomics.com/samples/cell-exp/1.1.0/pbmc3k/pbmc3k_filtered_gene_bc_matrices.tar.gz. The prostate cancer data was downloaded from http://www.prostatecellatlas.org/ with wget https://cellgeni.cog.sanger.ac.uk/prostatecellatlas/prostate_portal_300921.h5ad. 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