Evidence map›Paper›PMID 39939719›Full record

ArticleNature methods2025

Scalable co-sequencing of RNA and DNA from individual nuclei.

Timothy R Olsen, Pranay Talla, Romella K Sagatelian, Julia Furnari, Jeffrey N Bruce, Peter Canoll, Shan Zha, Peter A Sims

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. Article
  7. Early microglial priming in Alzheimer's disease revealed by ME-seq.bioRxiv : the preprint server for biology · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Year in review 2025.Nature methods · 2026
    Article
  14. Article
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  17. Article
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  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Timothy R OlsenDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
Pranay TallaDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-9826-4546
Romella K SagatelianDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
Julia FurnariDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY, USA.
Jeffrey N BruceDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-6844-0286
Peter CanollDepartment of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7001-0226
Shan ZhaDepartment of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Peter A SimsDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA. pas2182@cumc.columbia.edu.ORCID http://orcid.org/0000-0002-3921-4837

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Studying the evolution of drug resistance in prostate cancer at the single cell levelU54CA274506 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2023 to 2026
$9.1M
The Organoid and Cell Culture CoreP30DK132710 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Robert F. Schwabe · 2022 to 2026
$7.2M
Single Cell Analysis of the Infiltrative Margins of Glioblastoma and Post Treatment RecurrenceR01NS103473 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JEFFREY N BRUCE, Peter Canoll · 2017 to 2026
$4.3M
The role of DNA-PKcs in DNA repair, lymphocyte development, RNA metabolism and tumor suppressionR01CA275184 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Shan Zha · 2022 to 2026
$2.7M
NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA275184NCI NIH HHS U54 CA274506NIDDK NIH HHS P30 DK132710NINDS NIH HHS R01 NS103473U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA275184U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54CA274506U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS103473
6 · The paper itself

Abstract

The ideal technology for directly investigating the relationship between genotype and phenotype would analyze both RNA and DNA genome-wide and with single-cell resolution; however, existing tools lack the throughput required for comprehensive analysis of complex tumors and tissues. We introduce a highly scalable method for jointly profiling DNA and expression following nucleosome depletion (DEFND-seq). In DEFND-seq, nuclei are nucleosome-depleted, tagmented and separated into individual droplets for messenger RNA and genomic DNA barcoding. Once nuclei have been depleted of nucleosomes, subsequent steps can be performed using the widely available 10x Genomics droplet microfluidic technology and commercial kits. We demonstrate the production of high-complexity mRNA and gDNA sequencing libraries from thousands of individual nuclei from cell lines, fresh and archived surgical specimens for associating gene expression with both copy number and single-nucleotide variants.

Indexed as

Cell NucleusDNAHigh-Throughput Nucleotide SequencingRNASequence Analysis, DNASequence Analysis, RNAHumansNucleosomesPolymorphism, Single NucleotideRNA, MessengerSingle-Cell AnalysisDNANucleosomesRNARNA, Messenger

Identifiers

PMID39939719
PMCPMC12272635

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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.