CellO: comprehensive and hierarchical cell type classification of human cells with the Cell Ontology
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Abstract
Cell type annotation is a fundamental task in the analysis of single-cell RNA-sequencing data. In this work, we present CellO, a machine learning-based tool for annotating human RNA-seq data with the Cell Ontology. CellO enables accurate and standardized cell type classification of cell clusters by considering the rich hierarchical structure of known cell types. Furthermore, CellO comes pre-trained on a comprehensive data set of human, healthy, untreated primary samples in the Sequence Read Archive. CellO's comprehensive training set enables it to run out of the box on diverse cell types and achieves competitive or even superior performance when compared to existing state-of-the-art methods. Lastly, CellO's linear models are easily interpreted, thereby enabling exploration of cell-type-specific expression signatures across the ontology. To this end, we also present the CellO Viewer: a web application for exploring CellO's models across the ontology.
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Hierarchies of cell communities inferred from single-cell RNA sequencing data are typically compared to the Cell Ontology to determine which communities correspond to known versus novel cell types.
“Likewise, hierarchies of cell communities inferred from single-cell RNA seq data are typically compared to the CL to determine which communities correspond to known versus novel cell types (Bernstein et al., 2021; Hou et al., 2019).”
From Mapping the multiscale structure of biological systems (2021) · cites this paper as Bernstein et al., 2021
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SciPy 1.0: fundamental algorithms for scientific computing in Python
Virtanen, P., Gommers, R., Oliphant, T. E., Haberland, M., Reddy, T., Cournapeau, D., Burovski, E., Peterson, P., Weckesser, W., Bright, J., et al. (2020) · Nature Methods · doi:10.1038/s41592-019-0686-2 · Cited by 38,430 · see citing works
Robust enumeration of cell subsets from tissue expression profiles
Newman, A. M., Liu, C. L., Green, M. R., Gentles, A. J., Feng, W., Xu, Y., Hoang, C. D., Diehn, M., & Alizadeh, A. A. (2015) · Nature Methods · doi:10.1038/nmeth.3337 · Cited by 12,116 · see citing works
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · see citing works
SCANPY: large-scale single-cell gene expression data analysis
Wolf, F. A., Angerer, P., & Theis, F. J. (2018) · Genome Biology · doi:10.1186/s13059-017-1382-0 · Cited by 8,881 · see citing works
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353 · see citing works
NWChem: A comprehensive and scalable open-source solution for large scale molecular simulations
Valiev, M., Bylaska, E. J., Govind, N., Kowalski, K., Straatsma, T. P., van Dam, H. J. J., Wang, D., Nieplocha, J., Aprà, E., Windus, T. L., et al. (2010) · Computer Physics Communications · doi:10.1016/j.cpc.2010.04.018 · Cited by 5,794 · see citing works
From Louvain to Leiden: guaranteeing well-connected communities
Traag, V. A., Waltman, L., & van Eck, N. J. (2019) · Scientific Reports · doi:10.1038/s41598-019-41695-z · Cited by 5,635 · see citing works
Dimensionality reduction for visualizing single-cell data using UMAP
Becht, E., McInnes, L., Healy, J., Dutertre, C.-A., Kwok, I. W. H., Ng, L. G., Ginhoux, F., & Newell, E. W. (2019) · Nature Biotechnology · doi:10.1038/nbt.4314 · Cited by 5,358 · see citing works
Aran, D., Looney, A. P., Liu, L., Wu, E., Fong, V., Hsu, A., Chak, S., Naikawadi, R. P., Wolters, P. J., Abate, A. R., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0276-y · Cited by 4,984 · see citing works
xCell: digitally portraying the tissue cellular heterogeneity landscape
Aran, D., Hu, Z., & Butte, A. J. (2017) · Genome Biology · doi:10.1186/s13059-017-1349-1 · Cited by 4,397 · see citing works
Leinonen, R., Sugawara, H., & Shumway, M. F. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1019 · Cited by 2,760 · see citing works
The Gene Expression Omnibus Database
Clough, E., & Barrett, T. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3578-9_5 · Cited by 2,493 · see citing works
Smart-seq2 for sensitive full-length transcriptome profiling in single cells
Picelli, S., Björklund, Å. K., Faridani, O. R., Sagasser, S., Winberg, G., & Sandberg, R. (2013) · Nature Methods · doi:10.1038/nmeth.2639 · Cited by 2,358 · see citing works
Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types
Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., Elefant, N., Paul, F., Zaretsky, I., Mildner, A., Cohen, N., Jung, S., Tanay, A., et al. (2014) · Science · doi:10.1126/science.1247651 · Cited by 1,795 · see citing works
Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
Segerstolpe, Å., Palasantza, A., Eliasson, P., Andersson, E.-M., Andréasson, A.-C., Sun, X., Picelli, S., Sabirsh, A., Clausen, M., Bjursell, M. K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.020 · Cited by 1,550 · see citing works
CellMarker: a manually curated resource of cell markers in human and mouse
Zhang, X., Lan, Y., Xu, J., Quan, F., Zhao, E., Deng, C., Luo, T., Xu, L., Liao, G., Yan, M., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky900 · Cited by 1,524 · see citing works
Challenges in unsupervised clustering of single-cell RNA-seq data
Kiselev, V. Y., Andrews, T. S., & Hemberg, M. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0088-9 · Cited by 1,149 · see citing works
Identification and characterization of a fibroblast marker: FSP1.
Strutz, F. M., Okada, H., Lo, C. W., Danoff, T. M., Carone, R. L., Tomaszewski, J. E., & Neilson, E. G. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.130.2.393 · Cited by 1,075 · see citing works
Neuregulin 1 in neural development, synaptic plasticity and schizophrenia
Mei, L., & Xiong, W.-C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2392 · Cited by 1,030 · see citing works
Monaco, G., Lee, B., Xu, W., Mustafah, S., Hwang, Y. Y., Carré, C., Burdin, N., Visan, L., Ceccarelli, M., Poidinger, M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.041 · Cited by 958 · see citing works
Molecular diversity of midbrain development in mouse, human, and stem cells
La Manno, G., Gyllborg, D., Codeluppi, S., Nishimura, K., Salto, C., Zeisel, A., Borm, L. E., Stott, S. R. W., Toledo, E. M., Villaescusa, J. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.027 · Cited by 835 · see citing works
The origin and evolution of cell types
Arendt, D., Musser, J. M., Baker, C. V. H., Bergman, A., Cepko, C., Erwin, D. H., Pavlicev, M., Schlosser, G., Widder, S., Laubichler, M. D., et al. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.127 · Cited by 764 · see citing works
Uberon, an integrative multi-species anatomy ontology
Mungall, C. J., Torniai, C., Gkoutos, G. V., Lewis, S. E., & Haendel, M. A. (2012) · Genome biology · doi:10.1186/gb-2012-13-1-r5 · Cited by 732 · see citing works
A comparison of automatic cell identification methods for single-cell RNA sequencing data
Abdelaal, T., Michielsen, L., Cats, D., Hoogduin, D., Mei, H., Reinders, M. J. T., & Mahfouz, A. (2019) · Genome Biology · doi:10.1186/s13059-019-1795-z · Cited by 628 · see citing works
ENCODE data at the ENCODE portal
Sloan, C. A., Chan, E. T., Davidson, J. M., Malladi, V. S., Strattan, J. S., Hitz, B. C., Gabdank, I., Narayanan, A. K., Ho, M., Lee, B. T., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1160 · Cited by 549 · see citing works
Collin, M. P., McGovern, N. N., & Haniffa, M. A. (2013) · Immunology · doi:10.1111/imm.12117 · Cited by 499 · see citing works
Supervised classification enables rapid annotation of cell atlases
Pliner, H. A., Shendure, J., & Trapnell, C. (2019) · doi:10.1101/538652 · Cited by 498 · see citing works
An expression atlas of human primary cells: inference of gene function from coexpression networks
Mabbott, N. A., Baillie, J. K., Brown, H. K., Freeman, T. C., & Hume, D. A. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-632 · Cited by 477 · see citing works
scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data
Alquicira-Hernández, J., Sathe, A., Ji, H. P., Nguyen, Q. H., & Powell, J. E. (2019) · Genome biology · doi:10.1186/s13059-019-1862-5 · Cited by 474 · see citing works
Regenerative lineages and immune-mediated pruning in lung cancer metastasis
Laughney, A. M., Hu, J., Campbell, N. R., Bakhoum, S. F. W., Setty, M. N., Lavallée, V., Xie, Y., Masilionis, I., Carr, A., Kottapalli, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0750-6 · Cited by 470 · see citing works
Bard, J., Rhee, S. Y., & Ashburner, M. (2005) · Genome biology · doi:10.1186/gb-2005-6-2-r21 · Cited by 416 · see citing works
Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics
Puré, E., & Blomberg, R. (2018) · Oncogene · doi:10.1038/s41388-018-0275-3 · Cited by 394 · see citing works
Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling
Zhang, A. W., O’Flanagan, C. H., Chavez, E. A., Lim, J. L., Ceglia, N., McPherson, A., Wiens, M., Walters, P., Chan, T., Hewitson, B., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0529-1 · Cited by 373 · see citing works
Tan, Y., & Cahan, P. (2019) · Cell Systems · doi:10.1016/j.cels.2019.06.004 · Cited by 352 · see citing works
scCATCH: Automatic Annotation on Cell Types of Clusters from Single-Cell RNA Sequencing Data
Shao, X., Liao, J., Lu, X., Xue, R., Ai, N., & Fan, X. (2020) · iScience · doi:10.1016/j.isci.2020.100882 · Cited by 289 · see citing works
Role of Neuregulin-1/ErbB Signaling in Cardiovascular Physiology and Disease
Lemmens, K., Doggen, K., & Keulenaer, G. W. D. (2007) · Circulation · doi:10.1161/circulationaha.107.690487 · Cited by 288 · see citing works
CHETAH: a selective, hierarchical cell type identification method for single-cell RNA sequencing
de Kanter, J. K., Lijnzaad, P., Candelli, T., Margaritis, T., & Holstege, F. C. P. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz543 · Cited by 274 · see citing works
ACTINN: automated identification of cell types in single cell RNA sequencing
Ma, F., & Pellegrini, M. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btz592 · Cited by 252 · see citing works
Gremse, M., Chang, A., Schomburg, D., Grote, A., Scheer, M. P., Ebeling, C., & Schomburg, D. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq968 · Cited by 173 · see citing works
nVenn: generalized, quasi-proportional Venn and Euler diagrams
Pérez-Silva, J. G., Araujo‐Voces, M., & Quesada, V. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty109 · Cited by 154 · see citing works
The BLUEPRINT Data Analysis Portal
Fernández, J. M., de la Torre, V., Richardson, D., Royo, R., Puiggròs, M., Moncunill, V., Fragkogianni, S., Clarke, L., Flicek, P., Rico, D., et al. (2016) · Cell Systems · doi:10.1016/j.cels.2016.10.021 · Cited by 151 · see citing works
scMatch: a single-cell gene expression profile annotation tool using reference datasets
Hou, R., Denisenko, E., & Forrest, A. R. R. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz292 · Cited by 130 · see citing works
Update of the FANTOM web resource: high resolution transcriptome of diverse cell types in mammals
Lizio, M., Harshbarger, J., Abugessaisa, I., Noguchi, S., Kondo, A., Severin, J., Mungall, C., Arenillas, D. J., Mathelier, A., Medvedeva, Y. A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw995 · Cited by 115 · see citing works
Lieberman, Y., Rokach, L., & Shay, T. (2018) · PLoS ONE · doi:10.1371/journal.pone.0205499 · Cited by 113 · see citing works
Consistent probabilistic outputs for protein function prediction
Obozinski, G., Lanckriet, G. R. G., Grant, C. E., et al. (2008) · Genome biology · doi:10.1186/gb-2008-9-s1-s6 · Cited by 92 · see citing works
MetaSRA: normalized human sample-specific metadata for the Sequence Read Archive
Bernstein, M. N., Doan, A., & Dewey, C. N. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx334 · Cited by 87 · see citing works
Self-citationExplainers: Expert Explorations with Crafted Projections
Gleicher, M. L. (2013) · IEEE Transactions on Visualization and Computer Graphics · doi:10.1109/tvcg.2013.157 · Cited by 80 · see citing works
Self-citationDDX4 (VASA) Is Conserved in Germ Cell Development in Marsupials and Monotremes1
Hickford, D. E., Frankenberg, S., Pask, A. J., Shaw, G., & Renfree, M. B. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.111.091629 · Cited by 72 · see citing works
Pervasive Correlated Evolution in Gene Expression Shapes Cell and Tissue Type Transcriptomes
Liang, C., Musser, J. M., Cloutier, A., Prum, R. O., & Wagner, G. P. (2018) · Genome Biology and Evolution · doi:10.1093/gbe/evy016 · Cited by 58 · see citing works
Prediction of Human Phenotype Ontology terms by means of hierarchical ensemble methods
Notaro, M., Schubach, M., Robinson, P. N., & Valentini, G. (2017) · BMC Bioinformatics · doi:10.1186/s12859-017-1854-y · Cited by 40 · see citing works
Lee, Y.-S., Krishnan, A., Zhu, Q., & Troyanskaya, O. G. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt529 · Cited by 23 · see citing works
Yuan, M., Yang, X., Lin, J., Cao, X., Chen, F., Zhang, X., Li, Z., Zheng, G., Wang, X., Chen, X., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101273 · Cited by 15 · see citing works
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Mapping the multiscale structure of biological systems
Schaffer, L. V., & Ideker, T. (2021) · Cell Systems · doi:10.1016/j.cels.2021.05.012 · Cited by 75 · see citing works
- Authors
- Bernstein, M. N., Ma, Z., Gleicher, M., & Dewey, C. N.
- Affiliations
- Morgridge Institute for Research (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Dewey, Colin N.
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 24
- Issue
- 1
- Pages
- 101913
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC7753962
- OpenAlex
- W3113049731
- Cited by
- 45
- References
- 52
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 4 · 2021: 11 · 2020: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chan Zuckerberg Initiative
- National Institutes of Health
- National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- cell type classification, Cell Ontology, single-cell RNA sequencing, cell type annotation, cello, primary human cells
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