Evidence map›Paper›PMID 39482362›Full record

ReviewNature protocols2025

Seq-Scope: repurposing Illumina sequencing flow cells for high-resolution spatial transcriptomics.

Yongsung Kim, Weiqiu Cheng, Chun-Seok Cho, Yongha Hwang, Yichen Si, Anna Park, Mitchell Schrank, Jer-En Hsu, Angelo Anacleto, Jingyue Xi and 8 more

Abstract readReview
In one paragraph

Review in Nature protocols, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
–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

31 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Yongsung Kim *Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-2196-3063
Weiqiu Cheng *Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0003-4001-8662
Chun-Seok Cho *Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-9589-5745
Yongha HwangDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-4345-581X
Yichen SiDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.ORCID 0000-0001-5576-3054
Anna ParkDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-7323-9114
Mitchell SchrankDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jer-En HsuDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-2968-1853
Angelo AnacletoDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jingyue XiDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Myungjin KimDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ellen PedersenBiomedical Research Core Facilities Advanced Genomics Core, University of Michigan, Ann Arbor, MI, USA.
Olivia I KouesBiomedical Research Core Facilities Advanced Genomics Core, University of Michigan, Ann Arbor, MI, USA.
Thomas WilsonBiomedical Research Core Facilities Advanced Genomics Core, University of Michigan, Ann Arbor, MI, USA.
ChangHee LeeDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Goo JunHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Hyun Min KangDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA. hmkang@umich.edu.
Jun Hee LeeDepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. leeju@umich.edu.ORCID 0000-0002-2200-6011

Funding

Research Training in BiogerontologyT32AG000114 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT PLETCHER · 1985 to 2026
$12.4M
The NRF2-FBP1 crossregulatory loop and the control of healthy and diseased liver metabolismR01DK133448 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin, Jun Hee Lee · 2022 to 2026
$3.6M
Diabetes Progression with Metabolomic Profiling in Starr County Mexican AmericansR01DK118631 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI JUN, GOO · 2019 to 2023
$3.1M
Sestrins-mediated integration of leucine and exercise benefits for mitochondrial homeostasisR01AG079163 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Myungjin Kim, Jun Hee Lee · 2023 to 2026
$2.1M
Seq-Scope: Microscopic Examination of Spatial Single Cell Transcriptome in Cell and Tissue SenescenceUH3CA268091 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LEE, JUN HEE · 2023 to 2025
$1.7M
Leveraging long-range haplotypes in sequencing data to advance large scale genetic studiesR01HG011031 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOELLNER, SEBASTIAN · 2020 to 2023
$1.4M
Seq-Scope: Microscopic Examination of Spatial Single Cell Transcriptome in Cell and Tissue SenescenceUG3CA268091 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LEE, JUN HEE · 2021 to 2022
$1.1M
Beneficial effects of Sestrin protein for muscle health during aging and exerciseK01AG061236 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KIM, MYUNGJIN · 2019 to 2023
$600k
A. Alfred Taubman Medical Research Institute (Taubman Medical Research Institute) Taubman Institute Innovation ProjectNCI NIH HHS UG3 CA268091NCI NIH HHS UH3 CA268091NHGRI NIH HHS R01 HG011031NHLBI NIH HHS HHSN268201000021CNIA NIH HHS K01 AG061236NIA NIH HHS R01 AG079163NIA NIH HHS T32 AG000114NIDDK NIH HHS R01 DK118631NIDDK NIH HHS R01 DK133448U.S. Department of Health & Human Services | National Institutes of Health (NIH) K01AG061236 R01AG079163U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01HG011031 HHSN268201800002IU.S. Department of Health & Human Services | National Institutes of Health (NIH) T32AG000114
6 · The paper itself

Abstract

Spatial transcriptomics technologies aim to advance gene expression studies by profiling the entire transcriptome with intact spatial information from a single histological slide. However, the application of spatial transcriptomics is limited by low resolution, limited transcript coverage, complex procedures, poor scalability and high costs of initial setup and/or individual experiments. Seq-Scope repurposes the Illumina sequencing platform for high-resolution, high-content spatial transcriptome analysis, overcoming these limitations. It offers submicrometer resolution, high capture efficiency, rapid turnaround time and precise annotation of histopathology at a much lower cost than commercial alternatives. This protocol details the implementation of Seq-Scope with an Illumina NovaSeq 6000 sequencing flow cell, allowing the profiling of multiple tissue sections in an area of 7 mm × 7 mm or larger. We describe the preparation of a fresh-frozen tissue section for both histological imaging and sequencing library preparation and provide a streamlined computational pipeline with comprehensive instructions to integrate histological and transcriptomic data for high-resolution spatial analysis. This includes the use of conventional software tools for single-cell and spatial analysis, as well as our recently developed segmentation-free method for analyzing spatial data at submicrometer resolution. Aside from array production and sequencing, which can be done in batches, tissue processing, library preparation and running the computational pipeline can be completed within 3 days by researchers with experience in molecular biology, histology and basic Unix skills. Given its adaptability across various biological tissues, Seq-Scope establishes itself as an invaluable tool for researchers in molecular biology and histology.

Indexed as

Gene Expression ProfilingHigh-Throughput Nucleotide SequencingSequence Analysis, RNATranscriptomeAnimalsHumansSingle-Cell AnalysisSoftware

Identifiers

PMID39482362
PMCPMC11896753

What OpenQuestion holds

Textmetadata
LicenceTDM
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.