The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Effects of cell cycle variability on lineage and population measurements of mRNA abundance
Open accessPreprint — published as 10.1098/rsif.2020.0360 · Paper page
Abstract
Many models of gene expression do not explicitly incorporate a cell cycle description. Here we derive a theory describing how mRNA fluctuations for constitutive and bursty gene expression are influenced by stochasticity in the duration of the cell cycle and the timing of DNA replication. Analytical expressions for the moments show that omitting cell cycle duration introduces an error in the predicted mean number of mRNAs that is a monotonically decreasing function of η , which is proportional to the ratio of the mean cell cycle duration and the mRNA lifetime. By contrast, the error in the variance of the mRNA distribution is highest for intermediate values of η consistent with genome-wide measurements in many organisms. Using eukaryotic cell data, we estimate the errors in the mean and variance to be at most 3% and 25%, respectively. Furthermore, we derive an accurate negative binomial mixture approximation to the mRNA distribution. This indicates that stochasticity in the cell cycle can introduce fluctuations in mRNA numbers that are similar to the effect of bursty transcription. Finally, we show that for real experimental data, disregarding cell cycle stochasticity can introduce errors in the inference of transcription rates larger than 10%.
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.
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
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 8×
“145h−1 and N = 4 using the reported cell cycle duration and variability in [19] (see Appendix F), while replication is considered to occur at the middle of the cell cycle (w = 1/2).”
BackgroundMethodInfluential
Flagged first, then by citations
Research works printed but not linked: 57
- 10.1371/journal.pbio.0040309 · DOI · Paper page
- 10.1038/nsmb.1514 · DOI · Paper page
- 10.7554/eLife.12248 · DOI
- N. Van Kampen , Stochastic Processes in Physics and Chemistry. North-Holland Personal Library, Elsevier Science, 2011.
- 2020, Exact solution of stochastic gene expression models with bursting, cell cycle and replication dynamics, Phys. Rev. E, vol, 101, 032403, 10.1103/PhysRevE.101.032403 · DOI
- 10.1073/pnas.1910888117 · DOI
- I. G. Johnston and N. S. Jones , “Closed-form stochastic solutions for non-equilibrium dynamics and inheritance of cellular components over many cell divisions,” Proc. R. Soc. A Math. Phys. Eng. Sci., vol. 471, no. 2180, 2015. · DOI
- 10.1073/pnas.1013171108 · DOI
- 2020, Models of protein production along the cell cycle: An investigation of possible sources of noise, PLoS One, vol, 15, 1
- 10.1016/j.bpj.2014.05.004 · DOI
- P Thomas , “Making sense of snapshot data: Ergodic principle for clonal cell populations,” J. R. Soc. Interface, vol. 14, no. 136, 2017. · DOI
- M. Soltani and A. Singh , “Effects of cell-cycle-dependent expression on random fluctuations in protein levels,” R. Soc. Open Sci., vol. 3, no. 12, 2016. · DOI · Paper page
- 10.1371/journal.pcbi.1004972 · DOI
- 2019, Exactly solvable model of gene expression in a proliferating bacterial cell population with stochastic protein bursts and protein partitioning, Phys. Rev. E, 99, 042416, 10.1103/PhysRevE.99.042416 · DOI
- 10.1007/BF01190834 · DOI
- 10.1098/rsif.2013.0895 · DOI
- E. Gavagnin , S. T. Vittadello , G. Guanasingh , N. K. Haass , M. J. Simpson , T. Rogers , and C. A. Yates , “Synchronised oscillations in growing cell populations are explained by demographic noise,” bioRxiv, 2020. · DOI
- 10.1126/science.aax3072 · DOI
- 2017, A Multi-stage Representation of Cell Proliferation as a Markov Process, Bull. Math. Biol, 79, 2905, 10.1007/s11538-017-0356-4 · DOI
- 10.1073/pnas.1818680116 · DOI
- 10.1126/science.1213230 · DOI
- 10.1093/embo-reports/kve251 · DOI
- 1969, Time-Lapse Cinemicrographic Studies of X-Irradiated HeLa S3 Cells: I. Cell Progression and Cell Disintegration, Biophys. J, 9, 607, 10.1016/S0006-3495(69)86407-6 · DOI
- 10.1038/nmeth.2138 · DOI
- N. Brenner , E. Braun , A. Yoney , L. Susman , J. Rotella , and H. Salman , “Single-cell protein dynamics reproduce universal fluctuations in cell populations,” Eur. Phys. J. E, vol. 38, no. 9, 2015. · DOI
- 10.1038/nature06072 · DOI
- 10.1073/pnas.1811309115 · DOI
- 10.1016/j.cell.2005.04.013 · DOI
- 10.1101/gr.102764.109 · DOI
- 10.4161/cc.8.7.8042 · DOI
- 10.1101/gr.912603 · DOI
- 10.1073/pnas.092538799 · DOI
- 10.1016/S0076-6879(02)50954-X · DOI · Paper page
- 10.1006/jmbi.1999.2710 · DOI
- S. T. Vittadello , S. W. McCue , G. Gunasingh , N. K. Haass , and M. J. Simpson , “Mathematical models incorporating a multi-stage cell cycle replicate normally-hidden inherent synchronization in cell proliferation,” J. R. Soc. Interface, vol. 16, no. 157, 2019. · DOI · Paper page
- 2019, Simulation and inference algorithms for stochastic biochemical reaction networks: from basic concepts to state-of-the-art, J. R. Soc. Interface, 16, 20180943, 10.1098/rsif.2018.0943 · DOI
- 2020, Extrinsic Noise and Heavy-Tailed Laws in Gene Expression, Phys. Rev. Lett, 124, 108101, 10.1103/PhysRevLett.124.108101 · DOI
- 10.1038/ng.821 · DOI
- A. D. Cawte , P. J. Unrau , and D. S. Rueda , “Live cell imaging of single RNA molecules with fluorogenic Mango II arrays,” Nat. Commun., vol. 11, no. 1, 2020. · DOI
- 2018, An improved MS2 system for accurate reporting of the mRNA life cycle, Nat. Methods, 15, 81, 10.1038/nmeth.4502 · DOI
- 2019, Visualizing RNA dynamics in live cells with bright and stable fluorescent RNAs, Nat. Biotechnol, 37, 1287, 10.1038/s41587-019-0249-1 · DOI
- 10.1016/S0300-9084(02)01445-1 · DOI
- 10.1186/1747-1028-5-1 · DOI
- R. Sabi and T. Tuller , “Novel insights into gene expression regulation during meiosis revealed by translation elongation dynamics,” npj Syst. Biol. Appl., vol. 5, no. 1, 2019. · DOI
- 10.1016/j.molcel.2015.03.005 · DOI
- 10.1073/pnas.1322420111 · DOI
- 10.1126/science.1198817 · DOI · Paper page
- 10.1016/j.bpj.2013.12.011. · DOI
- 10.1128/MCB.24.3.945-953.2004 · DOI
- 10.1016/S1534-5807(03)00119-9 · DOI
- 10.1073/pnas.95.15.8660 · DOI
- 10.1093/emboj/cdg168 · DOI
- 10.1016/j.cell.2018.09.056 · DOI
- 10.1242/dev.059923 · DOI
- 10.1073/pnas.1912500117 · DOI
- 10.1126/science.1119623 · DOI · Paper page
- 10.1016/0022-5193(78)90326-0 · DOI
Metadata
- Authors
- Perez-Carrasco, R., Beentjes, C., & Grima, R.
- Affiliations
- University of Oxford (GB)
- University of Edinburgh (GB)
- Corresponding author
- Grima, Ramon
- Venue
- Journal of The Royal Society Interface
- Publisher
- openRxiv
- Published
- 2020-03-25
- Volume
- 17
- Issue
- 168
- Pages
- 20200360-20200360
- ISSN
- 1742-5662 (ISSN-L)
- PMC
- PMC7423421
- OpenAlex
- W3038366933
- Cited by
- 65
- References
- 1
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 14 · 2022: 19 · 2021: 11 · 2020: 2
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of The Royal Society Interface (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Leverhulme Trust (RPG-2018-423)
- Clarendon Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Physical Sciences › Mathematics › Mathematical Physics › Stochastic processes and statistical mechanics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- stochastic gene expression, DNA replication timing, mRNA levels, eukaryotic cells
- MeSH terms
- Cell Cycle, Cell Division, Models, Genetic, RNA, Messenger, Stochastic Processes
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
