The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells
Open accessAbstract
Defining the transcriptional dynamics of a temporal process such as cell differentiation is challenging owing to the high variability in gene expression between individual cells. Time-series gene expression analyses of bulk cells have difficulty distinguishing early and late phases of a transcriptional cascade or identifying rare subpopulations of cells, and single-cell proteomic methods rely on a priori knowledge of key distinguishing markers. Here we describe Monocle, an unsupervised algorithm that increases the temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points. Applied to the differentiation of primary human myoblasts, Monocle revealed switch-like changes in expression of key regulatory factors, sequential waves of gene regulation, and expression of regulators that were not known to act in differentiation. We validated some of these predicted regulators in a loss-of function screen. Monocle can in principle be used to recover single-cell gene expression kinetics from a wide array of cellular processes, including differentiation, proliferation and oncogenic transformation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Semi-supervised pseudotime analysis with Monocle 2 (Qiu et al., 2017a, 2017b; Trapnell et al., 2014) aligned microglial cells along a two-branched trajectory (Figure 2A).”
From The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques (2019) · cites this paper as Trapnell et al., 2014
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Monocle is an unsupervised algorithm designed for pseudotime inference analysis, capitalizing on the high variability in gene expression levels.”
From Single-cell sequencing to multi-omics: technologies and applications (2024) · cites this paper as [14]
In the citing paper
“Single cell transcriptome analysis enables the reconstruction of gene expression dynamics along differentiation trajectories (Setty et al., 2016; Shin et al., 2015; Trapnell et al., 2014).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Trapnell et al., 2014
In the citing paper
“Above the level of individual proteins and genomic loci, many recent studies use the technique of single-cell RNA sequencing to generate cell-cell networks, in which nodes represent the RNA expression state of an individual cell, and edges connect pairs of cells that are highly similar (Bendall et al., 2014; Trapnell et al., 2014).”
From Mapping the multiscale structure of biological systems (2021) · cites this paper as Trapnell et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
Self-citationHastie, T., & Tibshirani, R. (1986) · Statistical Science · doi:10.1214/ss/1177013604 · Cited by 12,575
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 12,145
Self-citationIndependent component analysis: algorithms and applications
Hyvärinen, A., & Erkki Oja, A. (2000) · Neural Networks · doi:10.1016/s0893-6080(00)00026-5 · Cited by 8,926
Brown, R. A., Hastie, T. J., & Tibshirani, R. J. (1991) · Biometrics · doi:10.2307/2532174 · Cited by 8,263
Estimation of Relationships for Limited Dependent Variables
Tobin, J. (1958) · Econometrica · doi:10.2307/1907382 · Cited by 6,996
Differential analysis of gene regulation at transcript resolution with RNA-seq
Trapnell, C., Hendrickson, D. G., Sauvageau, M., Goff, L., Rinn, J. L., & Pachter, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2450 · Cited by 3,492
Self-citationChromHMM: automating chromatin-state discovery and characterization
Ernst, J., & Kellis, M. (2012) · Nature Methods · doi:10.1038/nmeth.1906 · Cited by 2,457
Flagged first, then by citations
Cited by
Sorted by citations
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
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
Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055
Reversed graph embedding resolves complex single-cell trajectories
Qiu, X., Mao, Q., Tang, Y., Wang, L., Chawla, R., Pliner, H. A., & Trapnell, C. (2017) · Nature Methods · doi:10.1038/nmeth.4402 · Cited by 5,070
Self-citationLa Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M. E., Lönnerberg, P., Furlan, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0414-6 · Cited by 4,118
Metadata
- Authors
- Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N. J., Livak, K. J., Mikkelsen, T. S., & Rinn, J. L.
- Affiliations
- Broad Institute (US)
- Standard BioTools (United States) (US)
- Corresponding author
- Rinn, John L
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-03-23
- Volume
- 32
- Issue
- 4
- Pages
- 381-386
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4122333
- OpenAlex
- W1984883254
- Cited by
- 7,314
- References
- 43
- Citations by year
- 2026: 990 · 2025: 1109 · 2024: 999 · 2023: 933 · 2022: 849 · 2021: 716 · 2020: 621 · 2019: 389 · 2018: 298 · 2017: 176 · 2016: 139 · 2015: 73 · 2014: 15
- FWCI
- 55.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DP2OD006670, 1DP2OD00667)
- National Human Genome Research Institute (P50HG006193)
- National Institute of General Medical Sciences (P01GM099117)
- 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 › Gene expression and cancer classification
- Keywords
- monocle, single-cell RNA sequencing, cell differentiation, transcriptional dynamics, myogenesis, cell fate determination, gene regulatory networks, gene expression kinetics, loss-of-function screen
- MeSH terms
- Algorithms, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Humans, Transcription Factors, Reproducibility of Results, Gene Expression Profiling, Genomics, Muscle Development, Myoblasts, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
