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Record W4414183210 · doi:10.1038/s41592-025-02795-z

Spatial gene expression at single-cell resolution from histology using deep learning with GHIST

2025· article· en· W4414183210 on OpenAlex
Xiaohang Fu, Yue Cao, Beilei Bian, J. Dinny Graham, Nirmala Pathmanathan, Ellis Patrick, Jinman Kim, Jean Yang

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueNature Methods · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsnot available
FundersNational Health and Medical Research CouncilInnovation and Technology CommissionUniversity of SydneyUniversity of Guelph
KeywordsDeep learningIn silicoBenchmarkingTranscriptomeSpatial analysisFlexibility (engineering)ScalabilityGenomicsGenome

Abstract

fetched live from OpenAlex

The increased use of spatially resolved transcriptomics provides new biological insights into disease mechanisms. However, the high cost and complexity of these methods are barriers to broader application. Consequently, methods have been created to predict spot-based gene expression from routinely collected histology images. Recent benchmarking showed that current methodologies have limited accuracy and spatial resolution, constraining translational capacity. Here, we introduce GHIST, a deep learning-based framework that predicts spatial gene expression at single-cell resolution by leveraging subcellular spatial transcriptomics and synergistic relationships between multiple layers of biological information. We validated GHIST using public datasets and The Cancer Genome Atlas data, demonstrating its flexibility across different spatial resolutions and superior performance. Our results underscore the utility of in silico generation of single-cell spatial gene expression measurements and the capacity to enrich existing datasets with a spatially resolved omics modality, paving the way for scalable multi-omics analysis and biomarker identification.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.162
Threshold uncertainty score0.839

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.293
Teacher spread0.279 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it