Evidence map›Paper›PMID 35176222›Full record

ArticleCell stem cell2022

Whole-genome analysis of human embryonic stem cells enables rational line selection based on genetic variation.

Florian T Merkle, Sulagna Ghosh, Giulio Genovese, Robert E Handsaker, Seva Kashin, Daniel Meyer, Konrad J Karczewski, Colm O'Dushlaine, Carlos Pato, Michele Pato and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

29 citing papers in PubMed, 57 citations in OpenAlex.

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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

13 authors at 5 institutions in 3 countries.

Florian T MerkleDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Wellcome - MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: fm436@medschl.cam.ac.uk.
Sulagna GhoshDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Giulio GenoveseStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Robert E HandsakerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Seva KashinStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel MeyerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Konrad J KarczewskiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Colm O'DushlaineStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Carlos PatoDepartment of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA; Department of Psychiatry, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA.
Michele PatoDepartment of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA; Department of Psychiatry, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA.
Daniel G MacArthurDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Centre for Population Genomics, Garvan Institute of Medical Research, and UNSW Sydney, Sydney, NSW, Australia; Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Steven A McCarrollStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mccarroll@genetics.med.harvard.edu.
Kevin EgganDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: kevin.eggan@bmrn.com.
Broad Institute · USHarvard University · USJohnson University · USRutgers, The State University of New Jersey · USWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

African Ancestry Genomic Psychiatry CohortR01MH104964 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2015 to 2024
$16.7M
Latino Ancestry Genomic Psychiatry CohortR01MH123451 · NIMH · SUNY DOWNSTATE MEDICAL CENTER · PI BIGDELI, TIM BERNARD, FANOUS, AYMAN H · 2020 to 2025
$7.1M
Cellular models of hypocretin neuron loss in narcolepsyK99NS083713 · NINDS · HARVARD UNIVERSITY · PI MERKLE, FLORIAN TOBIAS · 2013 to 2014
$178k
Howard Hughes Medical InstituteMedical Research Council MC_UU_00014/5Medical Research Council MC_UU_12012/1Medical Research Council MC_UU_12012/5Medical Research Council MR/P501967/1Medical Research Council MR/R015724/1NIMH NIH HHS R01 MH104964NIMH NIH HHS R01 MH123451NINDS NIH HHS K99 NS083713Wellcome TrustWellcome Trust 211221/Z/18/Z
6 · The paper itself

Abstract

Despite their widespread use in research, there has not yet been a systematic genomic analysis of human embryonic stem cell (hESC) lines at a single-nucleotide resolution. We therefore performed whole-genome sequencing (WGS) of 143 hESC lines and annotated their single-nucleotide and structural genetic variants. We found that while a substantial fraction of hESC lines contained large deleterious structural variants, finer-scale structural and single-nucleotide variants (SNVs) that are ascertainable only through WGS analyses were present in hESC genomes and human blood-derived genomes at similar frequencies. Moreover, WGS allowed us to identify SNVs associated with cancer and other diseases that could alter cellular phenotypes and compromise the safety of hESC-derived cellular products transplanted into humans. As a resource to enable reproducible hESC research and safer translation, we provide a user-friendly WGS data portal and a data-driven scheme for cell line maintenance and selection.

Indexed as

Human Embryonic Stem CellsGenetic VariationGenome, HumanHumansNucleotidesWhole Genome SequencingNucleotidesembryonic stem cellgenetic variantgenomicspluripotentrational selectionresourcewhole-genome sequencing

Identifiers

PMID35176222
PMCPMC8900618
OpenAlexW4213359145

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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.