Evidence map›Paper›PMID 34057817›Full record

ArticleMolecular systems biology2021

Joint cell segmentation and cell type annotation for spatial transcriptomics.

Russell Littman, Zachary Hemminger, Robert Foreman, Douglas Arneson, Guanglin Zhang, Fernando Gómez-Pinilla, Xia Yang, Roy Wollman

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
6.6field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 103 citations in OpenAlex.

  1. Spatial Transcriptomics Analysis of Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Applications and development of in situ nucleic acid visualization techniques.Frontiers in bioengineering and biotechnology · 2026
    Review
  13. Artificial Intelligence Revolution in Transcriptomics: From Single Cells to Spatial Atlases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

4 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Russell LittmanDepartment of Integrative Biology and Physiology, UCLA, Los Angeles, CA, USA.
Zachary HemmingerInstitute of Quantitative and Computational Biosciences, UCLA, Los Angeles, CA, USA.
Robert ForemanInstitute of Quantitative and Computational Biosciences, UCLA, Los Angeles, CA, USA.
Douglas ArnesonInstitute of Quantitative and Computational Biosciences, UCLA, Los Angeles, CA, USA.
Guanglin ZhangDepartment of Integrative Biology and Physiology, UCLA, Los Angeles, CA, USA.
Fernando Gómez-PinillaDepartment of Integrative Biology and Physiology, UCLA, Los Angeles, CA, USA.
Xia YangDepartment of Integrative Biology and Physiology, UCLA, Los Angeles, CA, USA.ORCID 0000-0002-3971-038X
Roy WollmanDepartment of Integrative Biology and Physiology, UCLA, Los Angeles, CA, USA.ORCID 0000-0003-3865-2605
University of California, Los Angeles · USQuantitative BioSciences · US

Funding

Precision Medicine Approach: Using genomic information to guide TBI treatmentR01NS111378 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOMEZ-PINILLA, FERNANDO, YANG, XIA · 2020 to 2024
$2.9M
Spatiotemporal Molecular Substrates of TBI at Single Cell ResolutionR01NS117148 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOMEZ-PINILLA, FERNANDO, WOLLMAN, ROY · 2020 to 2024
$2.8M
Biomedical Big Data Training GrantT32CA201160 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PELLEGRINI, MATTEO · 2015 to 2015
$264k
NCI NIH HHS T32 CA201160NINDS NIH HHS R01 NS111378NINDS NIH HHS R01 NS117148
6 · The paper itself

Abstract

RNA hybridization-based spatial transcriptomics provides unparalleled detection sensitivity. However, inaccuracies in segmentation of image volumes into cells cause misassignment of mRNAs which is a major source of errors. Here, we develop JSTA, a computational framework for joint cell segmentation and cell type annotation that utilizes prior knowledge of cell type-specific gene expression. Simulation results show that leveraging existing cell type taxonomy increases RNA assignment accuracy by more than 45%. Using JSTA, we were able to classify cells in the mouse hippocampus into 133 (sub)types revealing the spatial organization of CA1, CA3, and Sst neuron subtypes. Analysis of within cell subtype spatial differential gene expression of 80 candidate genes identified 63 with statistically significant spatial differential gene expression across 61 (sub)types. Overall, our work demonstrates that known cell type expression patterns can be leveraged to improve the accuracy of RNA hybridization-based spatial transcriptomics while providing highly granular cell (sub)type information. The large number of newly discovered spatial gene expression patterns substantiates the need for accurate spatial transcriptomic measurements that can provide information beyond cell (sub)type labels.

Indexed as

Gene Expression ProfilingTranscriptomeAnimalsComputer SimulationMiceNeuronsRNA, MessengerRNA, Messengercell segmentation and annotationscRNAseqsingle cell multiomics integrationspatial differentially expressed genesspatial transcriptomics

Identifiers

PMID34057817
PMCPMC8166214
OpenAlexW3165800492

What OpenQuestion holds

Textmetadata
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.