Evidence map›Paper›PMID 31413257›Full record

ArticleNature communications2019

A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing.

Allegra A Petti, Stephen R Williams, Christopher A Miller, Ian T Fiddes, Sridhar N Srivatsan, David Y Chen, Catrina C Fronick, Robert S Fulton, Deanna M Church, Timothy J Ley

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 137 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% 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

137 citing papers in PubMed, 1 synthesis or guideline pooled it, 236 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Allegra A Petti *Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-6884-6107
Stephen R Williams *10x Genomics, Inc., Pleasanton, CA, USA.
Christopher A MillerDivision of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Ian T Fiddes10x Genomics, Inc., Pleasanton, CA, USA.
Sridhar N SrivatsanDivision of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
David Y ChenDivision of Dermatology, Washington University School of Medicine, St. Louis, MO, USA.
Catrina C FronickMcDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Robert S FultonMcDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
Deanna M ChurchInscripta, Inc., Boulder, CO, USA.ORCID http://orcid.org/0000-0003-4264-1853
Timothy J LeyDivision of Oncology, Washington University School of Medicine, St. Louis, MO, USA. timley@wustl.edu.
James S. McDonnell Foundation · US10X Genomics (United States) · USWashington University in St. Louis · US

Funding

Specimen Acquistition and Expression ProfilingP01CA101937 · NCI · WASHINGTON UNIVERSITY · PI PAYTON, JACQUELINE E. · 2003 to 2023
$58.8M
Washington University Paul Calabresi K12 Career Development Award for Clinical OncologyK12CA167540 · NCI · WASHINGTON UNIVERSITY · PI John F. Dipersio, Ramaswamy Govindan · 2012 to 2026
$11.7M
Molecular Pathogenesis of Acute Myeloid LeukemiaR35CA197561 · NCI · WASHINGTON UNIVERSITY · PI Timothy J. Ley · 2015 to 2026
$11.0M
COMPREHENSIVE INFORMATIC ANALYSES OF AML GENOMES AND EPIGENOMESR50CA211782 · NCI · WASHINGTON UNIVERSITY · PI Christopher A Miller · 2017 to 2026
$1.5M
NCI NIH HHS K12 CA167540NCI NIH HHS P01 CA101937NCI NIH HHS R35 CA197561NCI NIH HHS R50 CA211782
6 · The paper itself

Abstract

Virtually all tumors are genetically heterogeneous, containing mutationally-defined subclonal cell populations that often have distinct phenotypes. Single-cell RNA-sequencing has revealed that a variety of tumors are also transcriptionally heterogeneous, but the relationship between expression heterogeneity and subclonal architecture is unclear. Here, we address this question in the context of Acute Myeloid Leukemia (AML) by integrating whole genome sequencing with single-cell RNA-sequencing (using the 10x Genomics Chromium Single Cell 5' Gene Expression workflow). Applying this approach to five cryopreserved AML samples, we identify hundreds to thousands of cells containing tumor-specific mutations in each case, and use the results to distinguish AML cells (including normal-karyotype AML cells) from normal cells, identify expression signatures associated with subclonal mutations, and find cell surface markers that could be used to purify subclones for further study. This integrative approach for connecting genotype to phenotype is broadly applicable to any sample that is phenotypically and genetically heterogeneous.

Indexed as

Gene Expression ProfilingGenomicsGenotypeHumansLeukemia, Myeloid, AcuteMutationPhenotypePolymorphism, Single NucleotideRNASequence Analysis, RNASingle-Cell AnalysisWhole Genome SequencingRNA

Identifiers

PMID31413257
PMCPMC6694122
OpenAlexW2968098426

What Socratic 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 Socratic graph.