Evidence map›Paper›PMID 31118500›Full record

ArticleScientific reports2019

Multiplexed detection of RNA using MERFISH and branched DNA amplification.

Chenglong Xia, Hazen P Babcock, Jeffrey R Moffitt, Xiaowei Zhuang

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
–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

112 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
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  11. A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  12. Article
  13. Article
  14. Dissecting Normal and Abnormal Human Kidney Development Using Multiomics.Journal of the American Society of Nephrology : JASN · 2026
    Review
  15. Developing a Robust Multiround HCR-FISH Method Modified for Caenorhabditis elegans.Genes to cells : devoted to molecular & cellular mechanisms · 2026
    Article
  16. Mapping multipathology via spatial omic integration.Current opinion in biotechnology · 2026
    Review
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  18. Review
  19. Review
  20. Article

52 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

4 authors.

Chenglong XiaHoward Hughes Medical Institute, Department of Chemistry and Chemical Biology, and Department of Physics, Harvard University, Cambridge, MA, 02138, USA.
Hazen P BabcockCenter for Advanced Imaging, Harvard University, Cambridge, MA, 02138, USA.ORCID http://orcid.org/0000-0003-4835-3692
Jeffrey R MoffittProgram in Cellular and Molecular Medicine, Boston Children's Hospital; Department of Microbiology, Harvard Medical School, Boston, MA, 02115, USA. jeffrey.moffitt@childrens.harvard.edu.ORCID http://orcid.org/0000-0002-3836-3101
Xiaowei ZhuangHoward Hughes Medical Institute, Department of Chemistry and Chemical Biology, and Department of Physics, Harvard University, Cambridge, MA, 02138, USA. zhuang@chemistry.harvard.edu.ORCID http://orcid.org/0000-0002-6034-7853

Funding

Generation of novel cell type specific mouse genetic toolsU19MH114830 · NIMH · ALLEN INSTITUTE · PI TOLIAS, ANDREAS · 2017 to 2021
$64.7M
In situ transcriptome imaging in single cellsR01MH113094 · NIMH · HARVARD UNIVERSITY · PI DULAC, CATHERINE, ZHUANG, XIAOWEI · 2016 to 2020
$5.1M
Howard Hughes Medical InstituteNIMH NIH HHS R01 MH113094NIMH NIH HHS U19 MH114830
6 · The paper itself

Abstract

Multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows simultaneous imaging of numerous RNA species in their native cellular environment and hence spatially resolved single-cell transcriptomic measurements. However, the relatively modest brightness of signals from single RNA molecules can become limiting in a number of applications, such as increasing the imaging throughput, imaging shorter RNAs, and imaging samples with high degrees of background, such as some tissue samples. Here, we report a branched DNA (bDNA) amplification approach for MERFISH measurements. This approach produces a drastic signal increase in RNA FISH samples without increasing the fluorescent spot size for individual RNAs or increasing the variation in brightness from spot to spot, properties that are important for MERFISH imaging. Using this amplification approach in combination with MERFISH, we demonstrated RNA imaging and profiling with a near 100% detection efficiency. We further demonstrated that signal amplification improves MERFISH performance when fewer FISH probes are used for each RNA species, which should allow shorter RNAs to be imaged. We anticipate that the combination of bDNA amplification with MERFISH should facilitate many other applications and extend the range of biological questions that can be addressed by this technique in both cell culture and tissues.

Indexed as

Cell Line, TumorGene Expression ProfilingHigh-Throughput Screening AssaysHumansImage Processing, Computer-AssistedIn Situ Hybridization, FluorescenceNucleic Acid Amplification TechniquesOsteosarcomaRNARNA, NeoplasmSingle-Cell AnalysisRNARNA, Neoplasm

Identifiers

PMID31118500
PMCPMC6531529

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Registered trials

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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.