Evidence map›Paper›PMID 31227747›Full record

ArticleScientific reports2019

A Simple Procedure for Creating Scalable Phenotypic Screening Assays in Human Neurons.

BanuPriya Sridharan, Christopher Hubbs, Nerea Llamosas, Murat Kilinc, Fakhar U Singhera, Erik Willems, David R Piper, Louis Scampavia, Gavin Rumbaugh, Timothy P Spicer

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 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

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

  1. Pooled it
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  5. Article
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  8. Review
  9. The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.International journal of molecular sciences · 2021
    Review
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  12. The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
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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

10 authors.

BanuPriya SridharanThe Scripps Research Molecular Screening Center, Department of Molecular Medicine, Scripps Research, Jupiter, Florida, 33458, USA.
Christopher HubbsDepartment of Neuroscience, Scripps Research, Jupiter, Florida, 33458, USA.
Nerea LlamosasDepartment of Neuroscience, Scripps Research, Jupiter, Florida, 33458, USA.
Murat KilincGraduate School of Chemical and Biological Sciences, Scripps Research, Jupiter, Florida, 33458, USA.
Fakhar U SingheraThe Scripps Research Molecular Screening Center, Department of Molecular Medicine, Scripps Research, Jupiter, Florida, 33458, USA.
Erik WillemsCell Biology, Thermo Fisher Scientific, Carlsbad, California, 92008, USA.
David R PiperCell Biology, Thermo Fisher Scientific, Carlsbad, California, 92008, USA.
Louis ScampaviaThe Scripps Research Molecular Screening Center, Department of Molecular Medicine, Scripps Research, Jupiter, Florida, 33458, USA.
Gavin RumbaughThe Scripps Research Molecular Screening Center, Department of Molecular Medicine, Scripps Research, Jupiter, Florida, 33458, USA. grumbaug@scripps.edu.
Timothy P SpicerThe Scripps Research Molecular Screening Center, Department of Molecular Medicine, Scripps Research, Jupiter, Florida, 33458, USA. spicert@scripps.edu.

Funding

Integrated Platform for Discovery and Validation of Probes that Restore Protein Expression in Single-Gene Causes of Autism and Related DisordersR01MH113648 · NIMH · UNIVERSITY OF FLORIDA · PI MILLER, COURTNEY A, RUMBAUGH, GAVIN R · 2017 to 2023
$4.9M
NIMH NIH HHS R01 MH113648
6 · The paper itself

Abstract

Neurons created from human induced pluripotent stem cells (hiPSCs) provide the capability of identifying biological mechanisms that underlie brain disorders. IPSC-derived human neurons, or iNs, hold promise for advancing precision medicine through drug screening, though it remains unclear to what extent iNs can support early-stage drug discovery efforts in industrial-scale screening centers. Despite several reported approaches to generate iNs from iPSCs, each suffer from technological limitations that challenge their scalability and reproducibility, both requirements for successful screening assays. We addressed these challenges by initially removing the roadblocks related to scaling of iNs for high throughput screening (HTS)-ready assays. We accomplished this by simplifying the production and plating of iNs and adapting them to a freezer-ready format. We then tested the performance of freezer-ready iNs in an HTS-amenable phenotypic assay that measured neurite outgrowth. This assay successfully identified small molecule inhibitors of neurite outgrowth. Importantly, we provide evidence that this scalable iN-based assay was both robust and highly reproducible across different laboratories. These streamlined approaches are compatible with any iPSC line that can produce iNs. Thus, our findings indicate that current methods for producing iPSCs are appropriate for large-scale drug-discovery campaigns (i.e. >10e

Indexed as

Biological AssayCell DifferentiationCells, CulturedDrug DiscoveryDrug Evaluation, PreclinicalHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsNeuronal OutgrowthNeuronsPhenotypeReproducibility of Results

Identifiers

PMID31227747
PMCPMC6588600

What OpenQuestion holds

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LicenceCC BY
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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.