Evidence map›Paper›PMID 35969771›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Inferring gene regulation from stochastic transcriptional variation across single cells at steady state.

Anika Gupta, Jorge D Martin-Rufino, Thouis R Jones, Vidya Subramanian, Xiaojie Qiu, Emanuelle I Grody, Alex Bloemendal, Chen Weng, Sheng-Yong Niu, Kyung Hoi Min and 9 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.9field-weighted citation impact, top 3% of its field
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

24 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
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  5. Article
  6. Review
  7. Article
  8. Article
  9. Gene regulatory networks in disease and ageing.Nature reviews. Nephrology · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. A dynamical perspective: moving towards mechanism in single-cell transcriptomics.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

19 authors at 2 institutions in 1 country.

Anika GuptaBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Jorge D Martin-RufinoBroad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0002-7631-5442
Thouis R JonesBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Vidya SubramanianBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Xiaojie QiuWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Emanuelle I GrodyBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Alex BloemendalBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Chen WengBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Sheng-Yong NiuBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Kyung Hoi MinWhitehead Institute for Biomedical Research, Cambridge, MA 02142.
Arnav MehtaBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Kaite ZhangBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Layla SirajBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Aziz Al' KhafajiBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Vijay G SankaranBroad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0003-0044-443X
Soumya RaychaudhuriBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Brian ClearyBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Sharon GrossmanBroad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0001-6422-1134
Eric S LanderBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Broad Institute · USWhitehead Institute for Biomedical Research · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Predicting the impact of genetic variants, genes and pathways on human DiseaseU01HG012009 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ALKES L PRICE, Soumya Raychaudhuri · 2021 to 2026
$4.2M
NHGRI NIH HHS T32 HG002295NHGRI NIH HHS U01 HG012009NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Regulatory relationships between transcription factors (TFs) and their target genes lie at the heart of cellular identity and function; however, uncovering these relationships is often labor-intensive and requires perturbations. Here, we propose a principled framework to systematically infer gene regulation for all TFs simultaneously in cells at steady state by leveraging the intrinsic variation in the transcriptional abundance across single cells. Through modeling and simulations, we characterize how transcriptional bursts of a TF gene are propagated to its target genes, including the expected ranges of time delay and magnitude of maximum covariation. We distinguish these temporal trends from the time-invariant covariation arising from cell states, and we delineate the experimental and technical requirements for leveraging these small but meaningful cofluctuations in the presence of measurement noise. While current technology does not yet allow adequate power for definitively detecting regulatory relationships for all TFs simultaneously in cells at steady state, we investigate a small-scale dataset to inform future experimental design. This study supports the potential value of mapping regulatory connections through stochastic variation, and it motivates further technological development to achieve its full potential.

Indexed as

Gene Expression RegulationModels, BiologicalTranscription FactorsComputer SimulationGene Regulatory NetworksTranscription Factorsgene regulationsingle-cell transcriptomicstranscriptional bursting

Identifiers

PMID35969771
PMCPMC9407670
OpenAlexW4291804529

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.