Alignment of single-cell trajectories to compare cellular expression dynamics
Abstract
Single-cell RNA sequencing and high-dimensional cytometry can be used to generate detailed trajectories of dynamic biological processes such as differentiation or development. Here we present cellAlign, a quantitative framework for comparing expression dynamics within and between single-cell trajectories. By applying cellAlign to mouse and human embryonic developmental trajectories, we systematically delineate differences in the temporal regulation of gene expression programs that would otherwise be masked.
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We now detect genes that vary across a trajectory by regressing gene expression against pseudotime.
“While early approaches to find trajectory‐associated genes involved DE testing between cell clusters along a trajectory (Haghverdi et al, 2016; Alpert et al, 2018), we now detect genes that vary across a trajectory by regressing gene expression against pseudotime.”
From Current best practices in single-cell RNA-seq analysis: a tutorial (2019) · cites this paper as Alpert et al, 2018
Cites
Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N. J., Livak, K. J., Mikkelsen, T. S., & Rinn, J. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2859 · Cited by 7,314 · see citing works
Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells
Yan, L., Yang, M., Guo, H., Yang, L., Wu, J., Li, R., Liu, P., Lian, Y., Zheng, X., Yan, J., et al. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2660 · Cited by 1,740 · see citing works
Braude, P., Bolton, V. N., & Moore, S. S. (1988) · Nature · doi:10.1038/332459a0 · Cited by 1,462 · see citing works
Diffusion pseudotime robustly reconstructs lineage branching
Haghverdi, L., Büttner, M., Wolf, F. A., Buettner, F., & Theis, F. J. (2016) · Nature Methods · doi:10.1038/nmeth.3971 · Cited by 1,385 · see citing works
Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells
Deng, Q., Ramsköld, D., Reinius, B., & Sandberg, R. (2014) · Science · doi:10.1126/science.1245316 · Cited by 1,345 · see citing works
Computing and Visualizing Dynamic Time Warping Alignments inR: ThedtwPackage
Toni Giorgino, A. (2009) · Journal of Statistical Software · doi:10.18637/jss.v031.i07 · Cited by 1,263 · see citing works
Single-cell RNA-seq reveals dynamic paracrine control of cellular variation
Shalek, A. K., Satija, R., Shuga, J., Trombetta, J. J., Gennert, D., Lu, D., Chen, P., Gertner, R. S., Gaublomme, J. T., Yosef, N., et al. (2014) · Nature · doi:10.1038/nature13437 · Cited by 1,000 · see citing works
Bendall, S. C., Davis, K. L., Amir, E.-A. D., Tadmor, M. D., Simonds, E. F., Chen, T. J., Shenfeld, D. K., Nolan, G. P., & Pe’er, D. (2014) · Cell · doi:10.1016/j.cell.2014.04.005 · Cited by 906 · see citing works
The ConsensusPathDB interaction database: 2013 update
Kamburov, A., Stelzl, U., Lehrach, H. R., & Herwig, R. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1055 · Cited by 808 · see citing works
Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis
Shin, J., Berg, D. A., Zhu, Y., Shin, J. Y., Song, J., Bonaguidi, M. A., Enikolopov, G., Nauen, D. W., Christian, K. M., Ming, G.-L., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.07.013 · Cited by 784 · see citing works
Llorens-Bobadilla, E., Zhao, S., Baser, A., Saiz-Castro, G., Zwadlo, K., & Martin-Villalba, A. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.07.002 · Cited by 778 · see citing works
Endogenous Transcription Occurs at the 1-Cell Stage in the Mouse Embryo
Baly, C., Nguyen, E. D., & Debey, P. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1130 · Cited by 300 · see citing works
Yuan, Y., Chen, Y. P., Ni, S., Xu, A. G., Tang, L., Vingron, M., Somel, M., & Khaitovich, P. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-347 · Cited by 33 · see citing works
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Current best practices in single-cell RNA-seq analysis: a tutorial
Luecken, M. D., & Theis, F. J. (2019) · Molecular Systems Biology · doi:10.15252/msb.20188746 · Cited by 2,231 · see citing works
Integrative single-cell analysis
Stuart, T., & Satija, R. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0093-7 · Cited by 1,460 · see citing works
Computational principles and challenges in single-cell data integration
Argelaguet, R., Cuomo, A. S. E., Stegle, O., & Marioni, J. C. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00895-7 · Cited by 472 · see citing works
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Cannoodt, R., Saelens, W., Deconinck, L., & Saeys, Y. (2021) · Nature Communications · doi:10.1038/s41467-021-24152-2 · Cited by 124 · see citing works
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Chen, W. S., Zivanovic, N., van Dijk, D., Wolf, G., Bodenmiller, B., & Krishnaswamy, S. (2020) · Nature Methods · doi:10.1038/s41592-019-0689-z · Cited by 48 · see citing works
- Authors
- Alpert, A., Moore, L. S., Dubovik, T., & Shen-Orr, S. S.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Shen-Orr, Shai S
- ORCID
- Shen-Orr, Shai S
- Venue
- Nature Methods
- Published
- 2018-03-12
- Volume
- 15
- Issue
- 4
- Pages
- 267-270
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- OpenAlex
- W2789661952
- Cited by
- 96
- References
- 13
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 15 · 2023: 10 · 2022: 3 · 2021: 19 · 2020: 8 · 2019: 16 · 2018: 7
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- 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 Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- single-cell RNA sequencing, mass cytometry, gene expression dynamics, embryonic development, cell differentiation, temporal gene regulation, high-dimensional cytometry, mouse embryo, human embryo
- MeSH terms
- Animals, Base Sequence, Cytophotometry, Gene Expression Regulation, Humans, Sequence Analysis, RNA, Mice, Single-Cell Analysis, Transcriptome
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