Evidence map›Paper›PMID 40205439›Full record

ArticleGenome biology2025

Filtering cells with high mitochondrial content depletes viable metabolically altered malignant cell populations in cancer single-cell studies.

Josephine Yates, Agnieszka Kraft, Valentina Boeva

Abstract read
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

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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

3 authors.

Josephine Yates *Department of Computer Science, Institute for Machine Learning, ETH Zürich, Zurich, CH-8092, Switzerland.
Agnieszka Kraft *Department of Computer Science, Institute for Machine Learning, ETH Zürich, Zurich, CH-8092, Switzerland.
Valentina BoevaDepartment of Computer Science, Institute for Machine Learning, ETH Zürich, Zurich, CH-8092, Switzerland. valentina.boeva@inf.ethz.ch.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 205321_207931sSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung CRSII5_209524
6 · The paper itself

Abstract

backgroundSingle-cell transcriptomics has transformed our understanding of cellular diversity, yet noise from technical artifacts and low-quality cells can obscure key biological signals. A common practice is filtering out cells with a high percentage of mitochondrial RNA counts (pctMT), typically indicative of cell death. However, commonly used filtering thresholds, primarily derived from studies on healthy tissues, may be overly stringent for malignant cells, which often naturally exhibit higher baseline mitochondrial gene expression.

resultsWe examine nine public single-cell RNA-seq datasets from various cancers, including 441,445 cells from 134 patients, and public spatial transcriptomics data, assessing the viability of malignant cells with high pctMT. Our analysis reveals that malignant cells exhibit significantly higher pctMT than nonmalignant cells, without a notable increase in dissociation-induced stress scores. Malignant cells with high pctMT show metabolic dysregulation, including increased xenobiotic metabolism, relevant to therapeutic response. Analysis of pctMT in cancer cell lines further reveals links to drug resistance. We also observe associations between pctMT and malignant cell transcriptional heterogeneity, as well as patient clinical features.

conclusionsThis study provides insights into the functional characteristics of malignant cells with elevated pctMT, challenging current quality control practices in tumor single-cell RNA-seq analyses and offering potential improvements in data interpretation for future cancer studies.

Indexed as

MitochondriaNeoplasmsRNA, MitochondrialSingle-Cell AnalysisCell Line, TumorGene Expression ProfilingHumansRNA-SeqTranscriptomeRNA, MitochondrialCancerData qualityDrug resistanceMetabolismMT-RNASingle-cell RNA-seq

Identifiers

PMID40205439
PMCPMC11983838

What Socratic holds

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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 Socratic graph.