Evidence map›Paper›PMID 39849132›Full record

ArticleNature methods2025

Mapping the topography of spatial gene expression with interpretable deep learning.

Uthsav Chitra, Brian J Arnold, Hirak Sarkar, Kohei Sanno, Cong Ma, Sereno Lopez-Darwin, Benjamin J Raphael

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 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing 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

50 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Investigating Spatial Dynamics in Spatial Omics Data with StarTrail.Journal of the American Statistical Association · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Spatial architecture of development and disease.Nature reviews. Genetics · 2026
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Uthsav ChitraDepartment of Computer Science, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-6016-0960
Brian J ArnoldDepartment of Computer Science, Princeton University, Princeton, NJ, USA.
Hirak SarkarDepartment of Computer Science, Princeton University, Princeton, NJ, USA.
Kohei SannoDepartment of Computer Science, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0009-0001-4695-2993
Cong MaDepartment of Computer Science, Princeton University, Princeton, NJ, USA.
Sereno Lopez-DarwinLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Benjamin J RaphaelDepartment of Computer Science, Princeton University, Princeton, NJ, USA. braphael@princeton.edu.ORCID http://orcid.org/0000-0003-1274-048X

Funding

Comprehensive and Robust Tools for Analysis of Tumor Heterogeneity and EvolutionU24CA248453 · NCI · PRINCETON UNIVERSITY · PI Benjamin Raphael · 2020 to 2026
$4.7M
Pathway, Network and Spatiotemporal Integration of Cancer Genomics DataU24CA264027 · NCI · PRINCETON UNIVERSITY · PI RAPHAEL, BENJAMIN, YEH, JEN JEN · 2021 to 2025
$1.5M
NCI NIH HHS U24 CA248453NCI NIH HHS U24 CA264027U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U24CA248453
6 · The paper itself

Abstract

Spatially resolved transcriptomics technologies provide high-throughput measurements of gene expression in a tissue slice, but the sparsity of these data complicates analysis of spatial gene expression patterns. We address this issue by deriving a topographic map of a tissue slice-analogous to a map of elevation in a landscape-using a quantity called the isodepth. Contours of constant isodepths enclose domains with distinct cell type composition, while gradients of the isodepth indicate spatial directions of maximum change in expression. We develop GASTON (gradient analysis of spatial transcriptomics organization with neural networks), an unsupervised and interpretable deep learning algorithm that simultaneously learns the isodepth, spatial gradients and piecewise linear expression functions that model both continuous gradients and discontinuous variation in gene expression. We show that GASTON accurately identifies spatial domains and marker genes across several tissues, gradients of neuronal differentiation and firing in the brain, and gradients of metabolism and immune activity in the tumor microenvironment.

Indexed as

Deep LearningGene Expression ProfilingTranscriptomeAlgorithmsAnimalsBrainHumansMiceNeural Networks, ComputerTumor Microenvironment

Identifiers

PMID39849132
PMCPMC12370209

What OpenQuestion holds

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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 OpenQuestion graph.