Evidence map›Paper›PMID 36109685›Full record

ArticleNature biotechnology2023

Mostly natural sequencing-by-synthesis for scRNA-seq using Ultima sequencing.

Sean K Simmons, Gila Lithwick-Yanai, Xian Adiconis, Florian Oberstrass, Nika Iremadze, Kathryn Geiger-Schuller, Pratiksha I Thakore, Chris J Frangieh, Omer Barad, Gilad Almogy and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  3. Constellation illuminates rare disease genetics.medRxiv : the preprint server for health sciences · 2025
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  9. Review
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  12. Article
  13. Review
  14. Article
  15. Article
  16. Transcriptome-wide characterization of genetic perturbations.bioRxiv : the preprint server for biology · 2024
    Article
  17. Article
  18. Review
  19. Article
  20. 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

14 authors at 1 institution in 1 country.

Sean K Simmons *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gila Lithwick-Yanai *Ultima Genomics, Newark, CA, USA.
Xian Adiconis *Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Florian OberstrassUltima Genomics, Newark, CA, USA.
Nika IremadzeUltima Genomics, Newark, CA, USA.
Kathryn Geiger-SchullerKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6705-0681
Pratiksha I ThakoreKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Chris J FrangiehKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Omer BaradUltima Genomics, Newark, CA, USA.
Gilad AlmogyUltima Genomics, Newark, CA, USA.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6313-3570
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Doron LipsonUltima Genomics, Newark, CA, USA.
Joshua Z LevinKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. jlevin@broadinstitute.org.ORCID http://orcid.org/0000-0002-0170-3598
Broad Institute · US

Funding

Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
Novel sequencing by synthesis platform to greatly reduce the cost of nucleic acid sequencingR44HG010558 · NHGRI · ULTIMA GENOMICS, INC. · PI PRATT, MARK ROBIN · 2019 to 2019
$2.2M
Novel sequencing by synthesis chemistry to further reduce the cost of nucleic acid sequencingR44HG011060 · NHGRI · ULTIMA GENOMICS, INC. · PI MAZUR, DANIEL JOSEPH · 2020 to 2021
$2.0M
Mapping epigenetic regulatory circuits of Th17 pathogenicity in autoimmunediseaseF32AI138458 · NIAID · BROAD INSTITUTE, INC. · PI THAKORE, PRATIKSHA I · 2018 to 2020
$192k
Howard Hughes Medical InstituteNHGRI NIH HHS R44 HG010558NHGRI NIH HHS R44 HG011060NHGRI NIH HHS RM1 HG006193NIAID NIH HHS F32 AI138458
6 · The paper itself

Abstract

Here we introduce a mostly natural sequencing-by-synthesis (mnSBS) method for single-cell RNA sequencing (scRNA-seq), adapted to the Ultima genomics platform, and systematically benchmark it against current scRNA-seq technology. mnSBS uses mostly natural, unmodified nucleotides and only a low fraction of fluorescently labeled nucleotides, which allows for high polymerase processivity and lower costs. We demonstrate successful application in four scRNA-seq case studies of different technical and biological types, including 5' and 3' scRNA-seq, human peripheral blood mononuclear cells from a single individual and in multiplex, as well as Perturb-Seq. Benchmarking shows that results from mnSBS-based scRNA-seq are very similar to those using Illumina sequencing, with minor differences in results related to the position of reads relative to annotated gene boundaries, owing to single-end reads of Ultima being closer to gene ends than reads from Illumina. The method is thus compatible with state-of-the-art scRNA-seq libraries independent of the sequencing technology. We expect mnSBS to be of particular utility for cost-effective large-scale scRNA-seq projects.

Indexed as

Gene Expression ProfilingLeukocytes, MononuclearHumansNucleotidesSequence Analysis, RNASingle-Cell AnalysisSingle-Cell Gene Expression AnalysisNucleotides

Identifiers

PMID36109685
PMCPMC9931582
OpenAlexW4296029724

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.