Evidence map›Paper›PMID 39482463›Full record

ArticleNature methods2024

Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.

Alex R Lederer, Maxine Leonardi, Lorenzo Talamanca, Daniil M Bobrovskiy, Antonio Herrera, Colas Droin, Irina Khven, Hugo J F Carvalho, Alessandro Valente, Albert Dominguez Mantes and 4 more

Abstract read
In one paragraph

Article in Nature methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Alex R LedererLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-6381-5088
Maxine Leonardi *Laboratory of Computational and Systems Biology, Institute of Bioengineering, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-9780-9126
Lorenzo Talamanca *Laboratory of Computational and Systems Biology, Institute of Bioengineering, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-0846-7946
Daniil M BobrovskiyLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-6390-9930
Antonio HerreraLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-6248-1001
Colas DroinLaboratory of Computational and Systems Biology, Institute of Bioengineering, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-1171-2869
Irina KhvenLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Hugo J F CarvalhoLaboratory of Computational and Systems Biology, Institute of Bioengineering, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Alessandro ValenteLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Albert Dominguez MantesLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Pau Mulet ArabíLaboratory of Computational and Systems Biology, Institute of Bioengineering, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Luca PinelloMolecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA, USA.ORCID http://orcid.org/0000-0003-1109-3823
Felix NaefLaboratory of Computational and Systems Biology, Institute of Bioengineering, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. felix.naef@epfl.ch.ORCID http://orcid.org/0000-0001-9786-3037
Gioele La MannoLaboratory of Brain Development and Biological Data Science, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. gioele.lamanno@epfl.ch.ORCID http://orcid.org/0000-0003-1428-8757

Funding

Multiscale exploration of the functional non-coding genomeR35HG010717 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI PINELLO, LUCA · 2019 to 2023
$2.6M
NHGRI NIH HHS R35 HG010717Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030B_201267Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) PZ00P3_193445U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R35HG010717
6 · The paper itself

Abstract

Across biological systems, cells undergo coordinated changes in gene expression, resulting in transcriptome dynamics that unfold within a low-dimensional manifold. While low-dimensional dynamics can be extracted using RNA velocity, these algorithms can be fragile and rely on heuristics lacking statistical control. Moreover, the estimated vector field is not dynamically consistent with the traversed gene expression manifold. To address these challenges, we introduce a Bayesian model of RNA velocity that couples velocity field and manifold estimation in a reformulated, unified framework, identifying the parameters of an explicit dynamical system. Focusing on the cell cycle, we implement VeloCycle to study gene regulation dynamics on one-dimensional periodic manifolds and validate its ability to infer cell cycle periods using live imaging. We also apply VeloCycle to reveal speed differences in regionally defined progenitors and Perturb-seq gene knockdowns. Overall, VeloCycle expands the single-cell RNA sequencing analysis toolkit with a modular and statistically consistent RNA velocity inference framework.

Indexed as

AlgorithmsBayes TheoremCell CycleRNAAnimalsGene Expression RegulationHumansMiceSequence Analysis, RNASingle-Cell AnalysisTranscriptomeRNA

Identifiers

PMID39482463
PMCPMC11621032

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.