Evidence map›Paper›PMID 37645893›Full record

ArticlebioRxiv : the preprint server for biology2024

Deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial sections.

Patrick G Schupp, Samuel J Shelton, Daniel J Brody, Rebecca Eliscu, Brett E Johnson, Tali Mazor, Kevin W Kelley, Matthew B Potts, Michael W McDermott, Eric J Huang and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Patrick G SchuppDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.ORCID 0000-0001-5885-2386
Samuel J SheltonDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Daniel J BrodyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Rebecca EliscuDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Brett E JohnsonDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Tali MazorDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Kevin W KelleyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Matthew B PottsDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Michael W McDermottDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Eric J HuangDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Daniel A LimDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Russell O PieperDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Mitchel S BergerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Joseph F CostelloDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Joanna J PhillipsDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
Michael C OldhamDepartment of Neurological Surgery, University of California, San Francisco, San Francisco,California, USA.
University of California, San Francisco · US

Funding

Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
3-D spatial approach to discover genomic effectors of immunosuppression during malignant transformationR01CA244838 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F · 2020 to 2024
$2.7M
Decoding the molecular basis of cellular identity in adult malignant gliomasR01CA244621 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OLDHAM, MICHAEL CLARK · 2020 to 2024
$2.1M
Heparan sulfate proteoglycans as critical regulators of brain cancer malignancyR01NS081117 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PHILLIPS, JOANNA · 2012 to 2016
$1.7M
NCI NIH HHS R01 CA244621NCI NIH HHS R01 CA244838NCI NIH HHS T32 CA151022NINDS NIH HHS R01 NS081117
6 · The paper itself

Abstract

Tumors may contain billions of cells including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that is consistently expressed by astrocytoma truncal clones, including

Identifiers

PMID37645893
PMCPMC10461981
OpenAlexW4381855920

What OpenQuestion holds

Textmetadata
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.