Evidence map›Paper›PMID 30245212›Full record

ArticleStem cell reports2018

Reproducibility of Molecular Phenotypes after Long-Term Differentiation to Human iPSC-Derived Neurons: A Multi-Site Omics Study.

Viola Volpato, James Smith, Cynthia Sandor, Janina S Ried, Anna Baud, Adam Handel, Sarah E Newey, Frank Wessely, Moustafa Attar, Emma Whiteley and 32 more

Abstract read
In one paragraph

Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
–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

101 citing papers in PubMed.

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  17. Advancements in theFrontiers in toxicology · 2025
    Review
  18. Article
  19. Article
  20. Article

41 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

42 authors.

Viola VolpatoDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT UK.
James SmithGurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Cynthia SandorDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT UK.
Janina S RiedNeuroscience Discovery, Biology Department, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Anna BaudCentre for Translational Omics, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Adam HandelDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT UK.
Sarah E NeweyDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Frank WesselyDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT UK.
Moustafa AttarWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Emma WhiteleyDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Satyan ChintawarNuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX3 9DU, UK.
An VerheyenJanssen Research and Development, Beerse 2340, Belgium.
Thomas BartaInstitute of Genetic Medicine, Newcastle University, Newcastle NE1 3BZ, UK.
Majlinda LakoInstitute of Genetic Medicine, Newcastle University, Newcastle NE1 3BZ, UK.
Lyle ArmstrongInstitute of Genetic Medicine, Newcastle University, Newcastle NE1 3BZ, UK.
Caroline MuschetHelmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg 85764, Germany.
Anna ArtatiHelmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg 85764, Germany.
Carlo CusulinRoche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
Klaus ChristensenRoche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
Christoph PatschRoche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
Eshita SharmaWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Jerome NicodWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Philip BrownjohnGurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Victoria StubbsGurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Wendy E HeywoodCentre for Translational Omics, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Paul GissenMRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Roberta De FilippisNeuroscience Discovery, Biology Department, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Katharina JanssenNeuroscience Discovery, Biology Department, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Peter ReinhardtNeuroscience Discovery, Biology Department, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Jerzy AdamskiHelmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg 85764, Germany.
Ines RoyauxJanssen Research and Development, Beerse 2340, Belgium.
Pieter J PeetersJanssen Research and Development, Beerse 2340, Belgium.
Georg C TerstappenNeuroscience Discovery, Biology Department, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
Martin GrafRoche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
Frederick J LiveseyGurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK.
Colin J AkermanDepartment of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Kevin MillsCentre for Translational Omics, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Rory BowdenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
George NicholsonDepartment of Statistics, University of Oxford, Oxford OX1 3LB, UK.
Caleb WebberDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT UK. Electronic address: caleb.webber@dpag.ox.ac.uk.
M Zameel CaderNuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX3 9DU, UK. Electronic address: zameel.cader@ndcn.ox.ac.uk.
Viktor LakicsNeuroscience Discovery, Biology Department, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany. Electronic address: viktor.lakics@abbvie.com.

Funding

Medical Research Council MC_PC_16034Medical Research Council MC_UP_A320_1004Medical Research Council MC_UU_12021/4Medical Research Council MR/L023784/1Medical Research Council MR/R011338/1Parkinson's UK J-0901
6 · The paper itself

Abstract

Reproducibility in molecular and cellular studies is fundamental to scientific discovery. To establish the reproducibility of a well-defined long-term neuronal differentiation protocol, we repeated the cellular and molecular comparison of the same two iPSC lines across five distinct laboratories. Despite uncovering acceptable variability within individual laboratories, we detect poor cross-site reproducibility of the differential gene expression signature between these two lines. Factor analysis identifies the laboratory as the largest source of variation along with several variation-inflating confounders such as passaging effects and progenitor storage. Single-cell transcriptomics shows substantial cellular heterogeneity underlying inter-laboratory variability and being responsible for biases in differential gene expression inference. Factor analysis-based normalization of the combined dataset can remove the nuisance technical effects, enabling the execution of robust hypothesis-generating studies. Our study shows that multi-center collaborations can expose systematic biases and identify critical factors to be standardized when publishing novel protocols, contributing to increased cross-site reproducibility.

Indexed as

Cell DifferentiationCell LineFactor Analysis, StatisticalGene Expression RegulationGenotypeHumansInduced Pluripotent Stem CellsNeuronsPhenotypeProteomicsReproducibility of ResultsTranscriptomecortical neuronscross-site experimental variationgene expression profileinduced pluripotent stem cellmolecular profilingproteomic profilespublic-private partnershipreproducibilitysingle-cell sequencingstembancc

Identifiers

PMID30245212
PMCPMC6178242

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.