Evidence map›Paper›PMID 37885016›Full record

ArticleGenome biology2023

Pumping the brakes on RNA velocity by understanding and interpreting RNA velocity estimates.

Shijie C Zheng, Genevieve Stein-O'Brien, Leandros Boukas, Loyal A Goff, Kasper D Hansen

Abstract read
In one paragraph

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing 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

47 citing papers in PubMed.

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  12. Artificial Intelligence Revolution in Transcriptomics: From Single Cells to Spatial Atlases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  13. Article
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  17. Reconstructing Waddington's landscape from data.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Shijie C ZhengDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Genevieve Stein-O'BrienDepartment of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Leandros BoukasDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Loyal A GoffDepartment of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. loyalgoff@jhmi.edu.
Kasper D HansenDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. khansen@jhsph.edu.ORCID 0000-0003-0086-0687

Funding

Identification of enteric Juvenile Protective Factors and their role in stimulating neurogenesis in the adult and ageing Enteric Nervous SystemR01AG066768 · NIA · JOHNS HOPKINS UNIVERSITY · PI GOFF, LOYAL ANDREW, KULKARNI, SUBHASH · 2021 to 2025
$3.3M
Analysis of genomics datasets at a massive scaleR01GM121459 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI HANSEN, KASPER DANIEL · 2017 to 2021
$2.3M
Aging dependent transformation of oligodendrocyte precursor cellsR01AG072305 · NIA · JOHNS HOPKINS UNIVERSITY · PI BERGLES, DWIGHT E, GOFF, LOYAL ANDREW · 2021 to 2025
$2.0M
Data Science Tools to Increase Insight in Genomics DataR35GM149323 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Kasper Daniel Hansen · 2023 to 2026
$1.8M
Resolving Spatiotemporal Determinants of Cell Specification in Corticogenesis with Latent Space MethodsR00NS122085 · NINDS · JOHNS HOPKINS UNIVERSITY · PI STEIN-O'BRIEN, GENEVIEVE LAUREN · 2023 to 2025
$697k
Resolving Spatiotemporal Determinants of Cell Specification in Corticogenesis with Latent Space MethodsK99NS122085 · NINDS · JOHNS HOPKINS UNIVERSITY · PI STEIN-O'BRIEN, GENEVIEVE LAUREN · 2021 to 2022
$221k
NIA NIH HHS R01 AG066768NIA NIH HHS R01 AG072305NIGMS NIH HHS R01 GM121459NIGMS NIH HHS R35 GM149323NINDS NIH HHS K99 NS122085NINDS NIH HHS R00 NS122085
6 · The paper itself

Abstract

backgroundRNA velocity analysis of single cells offers the potential to predict temporal dynamics from gene expression. In many systems, RNA velocity has been observed to produce a vector field that qualitatively reflects known features of the system. However, the limitations of RNA velocity estimates are still not well understood.

resultsWe analyze the impact of different steps in the RNA velocity workflow on direction and speed. We consider both high-dimensional velocity estimates and low-dimensional velocity vector fields mapped onto an embedding. We conclude the transition probability method for mapping velocity estimates onto an embedding is effectively interpolating in the embedding space. Our findings reveal a significant dependence of the RNA velocity workflow on smoothing via the k-nearest-neighbors (k-NN) graph of the observed data. This reliance results in considerable estimation errors for both direction and speed in both high- and low-dimensional settings when the k-NN graph fails to accurately represent the true data structure; this is an unknown feature of real data. RNA velocity performs poorly at estimating speed in both low- and high-dimensional spaces, except in very low noise settings. We introduce a novel quality measure that can identify when RNA velocity should not be used.

conclusionsOur findings emphasize the importance of choices in the RNA velocity workflow and highlight critical limitations of data analysis. We advise against over-interpreting expression dynamics using RNA velocity, particularly in terms of speed. Finally, we emphasize that the use of RNA velocity in assessing the correctness of a low-dimensional embedding is circular.

Indexed as

ProbabilityCluster AnalysisRNA velocitySingle-cell RNA sequencing

Identifiers

PMID37885016
PMCPMC10601342

What OpenQuestion holds

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LicenceCC BY
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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.