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Trajectory-based differential expression analysis for single-cell sequencing data
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Abstract
Trajectory inference has radically enhanced single-cell RNA-seq research by enabling the study of dynamic changes in gene expression. Downstream of trajectory inference, it is vital to discover genes that are (i) associated with the lineages in the trajectory, or (ii) differentially expressed between lineages, to illuminate the underlying biological processes. Current data analysis procedures, however, either fail to exploit the continuous resolution provided by trajectory inference, or fail to pinpoint the exact types of differential expression. We introduce tradeSeq, a powerful generalized additive model framework based on the negative binomial distribution that allows flexible inference of both within-lineage and between-lineage differential expression. By incorporating observation-level weights, the model additionally allows to account for zero inflation. We evaluate the method on simulated datasets and on real datasets from droplet-based and full-length protocols, and show that it yields biological insights through a clear interpretation of the data.
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
UMAP: Uniform Manifold Approximation and Projection
McInnes, L., Healy, J., Saul, N., & Großberger, L. (2018) · Journal of Open Source Software · doi:10.21105/joss.00861 · Cited by 9,826
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
Bullard, J. H., Purdom, E., Hansen, K. D., & Dudoit, S. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-94 · Cited by 1,680
Self-citationA comparison of single-cell trajectory inference methods
Saelens, W., Cannoodt, R., Todorov, H., & Saeys, Y. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0071-9 · Cited by 1,670
Self-citationIdentification of a mesenchymal progenitor cell hierarchy in adipose tissue
Merrick, D., Sakers, A., Irgebay, Z., Okada, C., Calvert, C., Morley, M. P., Percec, I., & Seale, P. (2019) · Science · doi:10.1126/science.aav2501 · Cited by 664
Murphy, A. J., Akhtari, M., Tolani, S., Pagler, T., Bijl, N., Kuo, C.-L., Wang, M., Sanson, M., Abramowicz, S., Welch, C., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57559 · Cited by 521
Research works printed but not linked: 31
- Cannoodt, R., Saelens, W. & Saeys, Y. Computational methods for trajectory inference from single-cell transcriptomics. Eur. J. Immunol. 46, 2496–2506 (2016). · DOI
- Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018). · DOI · Paper page
- Lönnberg, T. et al. Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria. Sci. Immunol. 2, 3 (2017). · DOI · Paper page
- Qiu, X. et al. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979–982 (2017). · DOI · Paper page
- Byrnes, L. E. et al. Lineage dynamics of murine pancreatic development at single-cell resolution. Nat. Commun. 9, 3922 (2018). · DOI
- Herring, C. A. et al. Unsupervised trajectory analysis of single-cell RNA-Seq and imaging data reveals alternative tuft cell origins in the gut. Cell Syst. 6, 37–51 (2018). · DOI
- Nueda, M. J., Tarazona, S. & Conesa, A. Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series. Bioinformatics 30, 2598–2602 (2014). · DOI · Paper page
- Sanavia, T., Finotello, F. & Di Camillo, B. FunPat: function-based pattern analysis on RNA-seq time series data. BMC Genomics 16, S2 (2015). · DOI
- Bacher, R. et al. Trendy: segmented regression analysis of expression dynamics in high-throughput ordered profiling experiments. BMC Bioinform. 19, 380 (2018). · DOI
- Ji, Z. & Ji, H. TSCAN: Pseudo-time reconstruction and evaluation in single-cell RNA-seq analysis. Nucleic Acids Res. 44, e117–e117 (2016). · DOI · Paper page
- Lázaro-Gredilla, M., Van Vaerenbergh, S. & Lawrence, N. D. Overlapping mixtures of Gaussian processes for the data association problem. Pattern Recogn. 45, 1386–1395 (2012). · DOI
- Paul, F. et al. Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell 163, 1663–1677 (2015). · DOI · Paper page
- Fletcher, R. B. et al. Deconstructing olfactory stem cell trajectories at single-cell resolution. Cell Stem Cell 20, 817–830 (2017). · DOI
- Hegg, C. C., Jia, C., Chick, W. S., Restrepo, D. & Hansen, A. Microvillous cells expressing IP3 receptor type 3 in the olfactory epithelium of mice. Eur. J. Neurosci. 32, 1632–1645 (2010). · DOI
- Risso, D., Perraudeau, F., Gribkova, S., Dudoit, S. & Vert, J.-P. A general and flexible method for signal extraction from single-cell RNA-seq data. Nat. Commun. 9, 284 (2018). · DOI · Paper page
- Boukouvalas, A., Hensman, J. & Rattray, M. BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process. Genome Biol. 19, 65 (2018). · DOI
- Alpert, A., Moore, L. S., Dubovik, T. & Shen-Orr, S. S. Alignment of single-cell trajectories to compare cellular expression dynamics. Nat. Methods 15, 267–270 (2018). · DOI · Paper page
- Chen, H. et al. Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM. Nat. Commun. 10, 1903 (2019). · DOI · Paper page
- Wood, S. N., Pya, N. & Säfken, B. Smoothing parameter and model selection for general smooth models. J. Am. Stat. Assoc. 111, 1548–1563 (2016). · DOI · Paper page
- Risso, D. clusterExperiment and RSEC: A Bioconductor package and framework for clustering of single-cell and other large gene expression datasets. PLoS Comput. Biol. 14, e1006378 (2018). · DOI
- Heller, R., Manduchi, E., Grant, G. R. & Ewens, W. J. A flexible two-stage procedure for identifying gene sets that are differentially expressed. Bioinformatics 25, 1019–1025 (2009). · DOI
- Van den Berge, K., Soneson, C., Robinson, M. D. & Clement, L. stageR: a general stage-wise method for controlling the gene-level false discovery rate in differential expression and differential transcript usage. Genome Biol. 18, 151 (2017). · DOI · Paper page
- Lawrence, N. D. Gaussian process latent variable models for visualisation of high dimensional data. in NIPS’03 Proceedings of the 16th International Conference on Neural Information Processing Systems, Advances in neural information processing systems 16, 329–336 (2003).
- Fischer, D. S., Theis, F. J. & Yosef, N. Impulse model-based differential expression analysis of time course sequencing data. Nucleic Acids Res. 46, e119–e119 (2018). · DOI
- McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One 8, e61217 (2013). · DOI · Paper page
- McCarthy, D. J., Chen, Y. & Smyth, G. K. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288–4297 (2012). · DOI · Paper page
- Bolstad, B. M., Irizarry, R. A., Astrand, M. & Speed, T. P. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19, 185–93 (2003). · DOI · Paper page
- Fisher, R. A. Statistical Methods for Research Workers. https://scholar.google.com/scholar_lookup?title=Statisticalmethodsforresearchworkers&author=RA.Fisher&publication_year=1932 (Oliver & Boyd, Edinburgh, 1925).
- Soneson, C. & Robinson, M. D. iCOBRA: open, reproducible, standardized and live method benchmarking. Nat. Methods 13, 283–283 (2016). · DOI
- Kiselev, V. Y. et al. Perturbations of PIP3 signalling trigger a global remodelling of mRNA landscape and reveal a transcriptional feedback loop. Nucleic Acids Res. 43, gkv1015 (2015). · DOI
- Becht, E. et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2019). · DOI · Paper page
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Chaffin, M., Papangeli, I., Simonson, B., Akkad, A.-D., Hill, M. C., Arduini, A., Fleming, S. J., Melanson, M., Hayat, S., Kost-Alimova, M., et al. (2022) · Nature · doi:10.1038/s41586-022-04817-8 · Cited by 418
Triana, S., Vonficht, D., Jopp-Saile, L., Raffel, S., Lutz, R., Leonce, D., Antes, M., Hernández-Malmierca, P., Ordoñez-Rueda, D., Ramasz, B., et al. (2021) · Nature Immunology · doi:10.1038/s41590-021-01059-0 · Cited by 195
FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer
Han, M., Li, F., Zhang, Y., Dai, P., He, J., Li, Y., Zhu, Y., Zheng, J., Huang, H., Bai, F., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.10.011 · Cited by 166
Ellwanger, D. C., Wang, S., Brioschi, S., Shao, Z., Green, L., Case, R., Yoo, D., Weishuhn, D., Rathanaswami, P., Bradley, J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017742118 · Cited by 134
Defining blood-induced microglia functions in neurodegeneration through multiomic profiling
Mendiola, A. S., Yan, Z., Dixit, K., Johnson, J. R., Bouhaddou, M., Meyer-Franke, A., Shin, M.-G., Yong, Y., Agrawal, A., MacDonald, E., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01522-0 · Cited by 124
Spearheading future omics analyses using dyngen, a multi-modal simulator of single cells
Cannoodt, R., Saelens, W., Deconinck, L., & Saeys, Y. (2021) · Nature Communications · doi:10.1038/s41467-021-24152-2 · Cited by 124
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Vanneste, D., Bai, Q., Hasan, S., Peng, W., Pirottin, D., Schyns, J., Maréchal, P., Ruscitti, C., Meunier, M., Liu, Z., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01468-3 · Cited by 111
Generative modeling of single-cell gene expression for dose-dependent chemical perturbations
Kana, O., Nault, R., Filipovic, D., Marri, D., Zacharewski, T., & Bhattacharya, S. (2023) · Patterns · doi:10.1016/j.patter.2023.100817 · Cited by 44
Cross-regional homeostatic and reactive glial signatures in multiple sclerosis
Trobisch, T., Zulji, A., Stevens, N. A., Schwarz, S., Wischnewski, S., Öztürk, M., Perales-Patón, J., Haeussler, M., Saez-Rodriguez, J., Velmeshev, D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02497-2 · Cited by 40
Iturria-Medina, Y., Carbonell, F., Assadi, A., Adewale, Q., Khan, A. F., Baumeister, T. R., & Sanchez-Rodriguez, L. (2021) · Communications Biology · doi:10.1038/s42003-021-02133-x · Cited by 37
Das, S., Rai, A., Merchant, M. L., Cave, M. C., & Rai, S. N. (2021) · Genes · doi:10.3390/genes12121947 · Cited by 35
Fink, M., Njah, K., Patel, S. J., Cook, D. P., Man, V., Ruso, F., Rajan, A., Narimatsu, M., Obersterescu, A., Pye, M. J., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01550-4 · Cited by 33
Beliën, J., Swinnen, S., D’hondt, R., Verdú de Juan, L., Dedoncker, N., Matthys, P., Bauer, J., Vens, C., Moylett, S., & Dubois, B. (2024) · Nature Communications · doi:10.1038/s41467-024-49312-y · Cited by 32
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“14.0) were utilized (Van den Berge et al. 2020).”
Influential
Metadata
- Authors
- Van den Berge, K., Roux de Bézieux, H., Street, K., Saelens, W., Cannoodt, R., Saeys, Y., Dudoit, S., & Clement, L.
- Venue
- Nature Communications
- Published
- 2020-03-05
- Volume
- 11
- Issue
- 1
- Pages
- 1201-1201
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3009370296
- Cited by
- 828
- References
- 11
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- creativecommons.org/licenses/by/4.0 (tdm)
- creativecommons.org/licenses/by/4.0 (vor)
- Funders
- Belgian American Educational Foundation
- Fonds Wetenschappelijk Onderzoek (G062219N, 1246220N, 148095)
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