Evidence map›Paper›PMID 38925122›Full record

ArticleCell genomics2024

Synthetic DNA barcodes identify singlets in scRNA-seq datasets and evaluate doublet algorithms.

Ziyang Zhang, Madeline E Melzer, Keerthana M Arun, Hanxiao Sun, Carl-Johan Eriksson, Itai Fabian, Sagi Shaashua, Karun Kiani, Yaara Oren, Yogesh Goyal

Abstract read
In one paragraph

Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
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  5. Review
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  10. Fluctuation structure predicts genome-wide perturbation outcomes.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Mapping cell-cell fusion at single-cell resolution.bioRxiv : the preprint server for biology · 2025
    Article
  13. Improving doublet cell removal efficiency through multiple algorithm runs.Computational and structural biotechnology journal · 2025
    Article
  14. Article
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

10 authors.

Ziyang ZhangDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Center for Synthetic Biology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Madeline E MelzerDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Center for Synthetic Biology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: madeline.melzer@northwestern.edu.
Keerthana M ArunDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Center for Synthetic Biology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Hanxiao SunDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Center for Synthetic Biology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Carl-Johan ErikssonDepartment of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Itai FabianDepartment of Human Molecular Genetics & Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Sagi ShaashuaDepartment of Human Molecular Genetics & Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Karun KianiMedical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yaara OrenDepartment of Human Molecular Genetics & Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Yogesh GoyalDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Center for Synthetic Biology, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; CZ Biohub Chicago, Chicago, IL, USA. Electronic address: yogesh.goyal@northwestern.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Single-cell RNA sequencing (scRNA-seq) datasets contain true single cells, or singlets, in addition to cells that coalesce during the protocol, or doublets. Identifying singlets with high fidelity in scRNA-seq is necessary to avoid false negative and false positive discoveries. Although several methodologies have been proposed, they are typically tested on highly heterogeneous datasets and lack a priori knowledge of true singlets. Here, we leveraged datasets with synthetically introduced DNA barcodes for a hitherto unexplored application: to extract ground-truth singlets. We demonstrated the feasibility of our framework, "singletCode," to evaluate existing doublet detection methods across a range of contexts. We also leveraged our ground-truth singlets to train a proof-of-concept machine learning classifier, which outperformed other doublet detection algorithms. Our integrative framework can identify ground-truth singlets and enable robust doublet detection in non-barcoded datasets.

Indexed as

AlgorithmsDNA Barcoding, TaxonomicSingle-Cell AnalysisAnimalsHumansMachine LearningSequence Analysis, RNASingle-Cell Gene Expression Analysisbarcodingbenchmarkingdoublet detectionlineage tracingmachine learningscRNA-seqsingle-cell genomicssingletCodesinglets

Identifiers

PMID38925122
PMCPMC11293576

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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.