Evidence map›Paper›PMID 30765193›Full record

ArticleMolecular cell2019

Unravelling Intratumoral Heterogeneity through High-Sensitivity Single-Cell Mutational Analysis and Parallel RNA Sequencing.

Alba Rodriguez-Meira, Gemma Buck, Sally-Ann Clark, Benjamin J Povinelli, Veronica Alcolea, Eleni Louka, Simon McGowan, Angela Hamblin, Nikolaos Sousos, Nikolaos Barkas and 5 more

Abstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
187citing 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

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

  1. Pooled it
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  14. The Role and Impact of Non-driver Gene Mutations in Myelofibrosis.Current hematologic malignancy reports · 2026
    Review
  15. Sabotaged Integral HSC Heterogeneity Underlies Essential Thrombocythemia Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  16. Article
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  20. Article

127 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Alba Rodriguez-MeiraHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Gemma BuckHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Sally-Ann ClarkFlow Cytometry Facility, Medical Research Council, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Benjamin J PovinelliHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Veronica AlcoleaHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Eleni LoukaHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Simon McGowanMedical Research Council Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Angela HamblinNational Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK.
Nikolaos SousosHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Nikolaos BarkasHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Alice GiustacchiniHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Bethan PsailaHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK.
Sten Eirik W JacobsenHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Department of Cell and Molecular Biology, Wallenberg Institute for Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
Supat ThongjueaMedical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Adam J MeadHaematopoietic Stem Cell Biology Laboratory, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, UK. Electronic address: adam.mead@imm.ox.ac.uk.

Funding

Regulation by post-translation modifications in response to stressR35GM118104 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TOCZYSKI, DAVID PAUL · 2016 to 2025
$7.2M
Cancer Research UK 26988Cancer Research UK 27125Cancer Research UK 27723Cancer Research UK 28051Cancer Research UK 29034Medical Research Council G0501838Medical Research Council G0801073Medical Research Council G0902418Medical Research Council G84/6443Medical Research Council MC_PC_12020Medical Research Council MC_UU_00016/15Medical Research Council MC_UU_00016/5Medical Research Council MC_UU_12009/16Medical Research Council MC_UU_12009/5Medical Research Council MR/L006340/1Medical Research Council MR/M00919X/1NIGMS NIH HHS R35 GM118104
6 · The paper itself

Abstract

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving transcriptional heterogeneity. However, its application to studying cancerous tissues is currently hampered by the lack of coverage across key mutation hotspots in the vast majority of cells; this lack of coverage prevents the correlation of genetic and transcriptional readouts from the same single cell. To overcome this, we developed TARGET-seq, a method for the high-sensitivity detection of multiple mutations within single cells from both genomic and coding DNA, in parallel with unbiased whole-transcriptome analysis. Applying TARGET-seq to 4,559 single cells, we demonstrate how this technique uniquely resolves transcriptional and genetic tumor heterogeneity in myeloproliferative neoplasms (MPN) stem and progenitor cells, providing insights into deregulated pathways of mutant and non-mutant cells. TARGET-seq is a powerful tool for resolving the molecular signatures of genetically distinct subclones of cancer cells.

Indexed as

Genetic HeterogeneityHigh-Throughput Nucleotide SequencingMutationSequence Analysis, RNASingle-Cell AnalysisBiomarkers, TumorDNA Mutational AnalysisHumansJurkat CellsK562 CellsLeukemiaReproducibility of ResultsSchizosaccharomycesBiomarkers, TumorcancerhematopoiesisHeterogeneityleukemiamutationsmyeloproliferative neoplasmsequencingsingle-cellTARGET-seqtranscriptomics

Identifiers

PMID30765193
PMCPMC6436961

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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.