Evidence map›Paper›PMID 37864274›Full record

ArticleGenome biology2023

Performance of computational algorithms to deconvolve heterogeneous bulk ovarian tumor tissue depends on experimental factors.

Ariel A Hippen, Dalia K Omran, Lukas M Weber, Euihye Jung, Ronny Drapkin, Jennifer A Doherty, Stephanie C Hicks, Casey S Greene

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 43 citations in OpenAlex.

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  13. NADCell death & disease · 2025
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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

8 authors at 5 institutions in 1 country.

Ariel A HippenDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.
Dalia K OmranPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lukas M WeberDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Euihye JungPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ronny DrapkinPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jennifer A DohertyHuntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Stephanie C HicksDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Casey S GreeneDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. casey.s.greene@cuanschutz.edu.ORCID http://orcid.org/0000-0001-8713-9213
Cancer Research Center · USJohns Hopkins University · USTranslational Therapeutics (United States) · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Utah · US

Funding

SPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Ronny I DRAPKIN, IE-MING SHIH · 2018 to 2026
$20.5M
Characterization of high-grade serous ovarian cancer subtypes via single-cell profilingR01CA237170 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DOHERTY, JENNIFER A., GREENE, CASEY S · 2019 to 2024
$3.0M
NCI NIH HHS P50 CA228991NCI NIH HHS R01 CA237170
6 · The paper itself

Abstract

backgroundSingle-cell gene expression profiling provides unique opportunities to understand tumor heterogeneity and the tumor microenvironment. Because of cost and feasibility, profiling bulk tumors remains the primary population-scale analytical strategy. Many algorithms can deconvolve these tumors using single-cell profiles to infer their composition. While experimental choices do not change the true underlying composition of the tumor, they can affect the measurements produced by the assay.

resultsWe generated a dataset of high-grade serous ovarian tumors with paired expression profiles from using multiple strategies to examine the extent to which experimental factors impact the results of downstream tumor deconvolution methods. We find that pooling samples for single-cell sequencing and subsequent demultiplexing has a minimal effect. We identify dissociation-induced differences that affect cell composition, leading to changes that may compromise the assumptions underlying some deconvolution algorithms. We also observe differences across mRNA enrichment methods that introduce additional discrepancies between the two data types. We also find that experimental factors change cell composition estimates and that the impact differs by method.

conclusionsPrevious benchmarks of deconvolution methods have largely ignored experimental factors. We find that methods vary in their robustness to experimental factors. We provide recommendations for methods developers seeking to produce the next generation of deconvolution approaches and for scientists designing experiments using deconvolution to study tumor heterogeneity.

Indexed as

Gene Expression ProfilingOvarian NeoplasmsAlgorithmsFemaleHumansSequence Analysis, RNATranscriptomeTumor MicroenvironmentDeconvolutionSingle-cell RNA-seqTumor composition

Identifiers

PMID37864274
PMCPMC10588129
OpenAlexW4387814741

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LicenceCC BY
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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.