Evidence map›Paper›PMID 32383753›Full record

ArticleNucleic acids research2020

dotdotdot: an automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues.

Kristen R Maynard, Madhavi Tippani, Yoichiro Takahashi, BaDoi N Phan, Thomas M Hyde, Andrew E Jaffe, Keri Martinowich

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
5.3field-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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Article
  7. Applications and development of in situ nucleic acid visualization techniques.Frontiers in bioengineering and biotechnology · 2026
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  8. Transcriptomic Analysis of the Human Habenula in Schizophrenia.The American journal of psychiatry · 2025
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  14. Stimulus-Dependent Expression ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
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  15. Overexpression of theLearning & memory (Cold Spring Harbor, N.Y.) · 2025
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  19. Overexpression of thebioRxiv : the preprint server for biology · 2024
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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

7 authors at 1 institution in 1 country.

Kristen R MaynardLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Madhavi TippaniLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Yoichiro TakahashiLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
BaDoi N PhanLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Thomas M HydeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Andrew E JaffeLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Keri MartinowichLieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
Johns Hopkins University · US

Funding

Epigenomic contribution to the antidepressant responseR21MH118725 · NIMH · LIEBER INSTITUTE, INC. · PI MARTINOWICH, KERI · 2018 to 2019
$513k
NIMH NIH HHS R21 MH118725
6 · The paper itself

Abstract

Multiplex single-molecule fluorescent in situ hybridization (smFISH) is a powerful method for validating RNA sequencing and emerging spatial transcriptomic data, but quantification remains a computational challenge. We present a framework for generating and analyzing smFISH data in complex tissues while overcoming autofluorescence and increasing multiplexing capacity. We developed dotdotdot (https://github.com/LieberInstitute/dotdotdot) as a corresponding software package to quantify RNA transcripts in single nuclei and perform differential expression analysis. We first demonstrate robustness of our platform in single mouse neurons by quantifying differential expression of activity-regulated genes. We then quantify spatial gene expression in human dorsolateral prefrontal cortex (DLPFC) using spectral imaging and dotdotdot to mask lipofuscin autofluorescence. We lastly apply machine learning to predict cell types and perform downstream cell type-specific expression analysis. In summary, we provide experimental workflows, imaging acquisition and analytic strategies for quantification and biological interpretation of smFISH data in complex tissues.

Indexed as

AutomationSingle Molecule ImagingSoftwareAdolescentAdultAnimalsHumansImage Processing, Computer-AssistedIn Situ Hybridization, FluorescenceLipofuscinMachine LearningMaleMiceNeuronsOrgan SpecificityPrefrontal CortexLipofuscinRNA, Messenger

Identifiers

PMID32383753
PMCPMC7293004
OpenAlexW3022553019

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.