Evidence map›Paper›PMID 38365907›Full record

ArticleScientific reports2024

Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids.

Davide Capauto, Yifan Wang, Feinan Wu, Scott Norton, Jessica Mariani, Fumitaka Inoue, Gregory E Crawford, Nadav Ahituv, Alexej Abyzov, Flora M Vaccarino

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  8. Just a SNP away: The future ofCell insight · 2025
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  11. AnFrontiers in genetics · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 2 countries.

Davide Capauto *Child Study Center, Yale University, New Haven, CT, 06520, USA.
Yifan Wang *Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Feinan WuChild Study Center, Yale University, New Haven, CT, 06520, USA.
Scott NortonChild Study Center, Yale University, New Haven, CT, 06520, USA.
Jessica MarianiChild Study Center, Yale University, New Haven, CT, 06520, USA.
Fumitaka InoueInstitute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan.
Gregory E CrawfordDepartment of Pediatrics, Duke University, Durham, NC, 27708, USA.
Nadav AhituvDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Alexej AbyzovDepartment of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA. abyzov.alexej@mayo.edu.
Flora M VaccarinoChild Study Center, Yale University, New Haven, CT, 06520, USA. flora.vaccarino@yale.edu.
Yale University · USMayo Clinic · USDuke University · USKyoto University · JPUniversity of California, San Francisco · USYale Cancer Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Neurobiology of Autism With MacrocephalyR01MH109648 · NIMH · YALE UNIVERSITY · PI VACCARINO, FLORA M · 2016 to 2021
$3.3M
Massively parallel characterization of psychiatric disease associated regulatory elements in defined cell typesU01MH116438 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, POLLARD, KATHERINE S. · 2018 to 2021
$2.7M
High Performance Computing Instrumentation for the Yale Center for Genome AnalysisS10OD030363 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2022 to 2022
$1.2M
3/3 Chromatin regulation during brain development and in ASDR56MH114901 · NIMH · DUKE UNIVERSITY · PI CRAWFORD, GREGORY E · 2018 to 2018
$356k
2/3 Chromatin regulation during brain development and in ASDR56MH114899 · NIMH · MAYO CLINIC ROCHESTER · PI ABYZOV, ALEXEJ · 2018 to 2018
$130k
NCATS NIH HHS UL1 TR001863NIH HHS S10 OD030363NIMH NIH HHS R01 MH109648NIMH NIH HHS R56 MH114899NIMH NIH HHS R56 MH114901NIMH NIH HHS U01 MH116438
6 · The paper itself

Abstract

Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ~ 7000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ~ 35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neurodevelopment. The temporal specificity was further supported by the correlation of activity with gene expression. Our findings provide a valuable gene regulatory resource to the scientific community.

Indexed as

Gene Expression RegulationRegulatory Sequences, Nucleic AcidEnhancer Elements, GeneticHumansOrganoidsProsencephalon

Identifiers

PMID38365907
PMCPMC10873509
OpenAlexW4391876226

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.