SpaTM: topic models for inferring spatially informed transcriptional programs
Bibliographic record
Abstract
Spatial transcriptomics enables the contextualization of gene expression with spatial organization, advancing our understanding of development, disease, and tissue architecture. However, existing analysis pipelines require multiple tools to explore spatial domains, and few methods can jointly analyse spatial data from annotation-free and annotation-guided perspectives with high interpretability. We therefore propose the Spatial Topic Model (SpaTM), a topic-modelling framework capable of annotation-guided and annotation-free analysis of spatial transcriptomes. SpaTM can learn gene programs that represent histology-based annotations while also inferring spatial domains with an annotation-free approach if manual annotations are limited or noisy. In benchmarking experiments, SpaTM achieves competitive performance at spatial label prediction and clustering when compared with existing state-of-the-art methods. We demonstrate SpaTM's interpretability by using topic mixtures to capture transcriptional programs in dorsolateral prefrontal cortex and ductal carcinoma samples and show how its intuitive framework facilitates the integration of spatial transcriptomics tasks. Finally, we showcase how SpaTM can extend the analysis of large-scale snRNA-seq atlases in human brains with Major Depressive Disorder. Overall, SpaTM provides a unified and interpretable analysis framework for spatial transcriptomics, enabling competitive performance in multiple tasks while inferring biologically informed gene programs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".