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Record W4404829198 · doi:10.1002/advs.202410081

Accurate Spatial Heterogeneity Dissection and Gene Regulation Interpretation for Spatial Transcriptomics using Dual Graph Contrastive Learning

2024· article· en· W4404829198 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueAdvanced Science · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsUniversity of Toronto
FundersNational Natural Science Foundation of China
KeywordsComputer scienceInterpretabilitySpatial analysisArtificial intelligenceGraphGraph embeddingSpatial contextual awarenessCluster analysisPattern recognition (psychology)Computational biologyEmbeddingBiologyTheoretical computer scienceMathematics

Abstract

fetched live from OpenAlex

Recent advances in spatial transcriptomics have enabled simultaneous preservation of high-throughput gene expression profiles and the spatial context, enabling high-resolution exploration of distinct regional characterization in tissue. To effectively understand the underlying biological mechanisms within tissue microenvironments, there is a requisite for methods that can accurately capture external spatial heterogeneity and interpret internal gene regulation from spatial transcriptomics data. However, current methods for region identification often lack the simultaneous characterizing of spatial structure and gene regulation, thereby limiting the ability of spatial dissection and gene interpretation. Here, stDCL is developed, a dual graph contrastive learning method to identify spatial domains and interpret gene regulation in spatial transcriptomics data. stDCL adaptively incorporates gene expression data and spatial information via a graph embedding autoencoder, thereby preserving critical information within the latent embedding representations. In addition, dual graph contrastive learning is proposed to train the model, ensuring that the latent embedding representation closely resembles the actual spatial distribution and exhibits cluster similarity. Benchmarking stDCL against other state-of-the-art clustering methods using complex cortex datasets demonstrates its superior accuracy and effectiveness in identifying spatial domains. Our analysis of the imputation matrices generated by stDCL reveals its capability to reconstruct spatial hierarchical structures and refine differential expression assessment. Furthermore, it is demonstrated that the versatility of stDCL in interpretability of gene regulation, spatial heterogeneity at high resolution, and embryonic developmental patterns. In addition, it is also showed that stDCL can successfully annotate disease-associated astrocyte subtypes in Alzheimer's disease and unravel multiple relevant pathways and regulatory mechanisms.

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: Empirical
Teacher disagreement score0.478
Threshold uncertainty score0.576

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 integrity0.0000.000
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 head0.015
GPT teacher head0.284
Teacher spread0.269 · 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