Cross-expression meta-analysis of mouse brain slices reveals coordinated gene expression across spatially adjacent cells
Bibliographic record
Abstract
BACKGROUND: Spatial transcriptomics allow us to ask a fundamental question: how do nearby cells orchestrate their gene expression? Rather than focus on how these cells (samples) communicate with each other, we reframe the problem to investigate how genes (features) coordinate their expression between neighboring cells. To this end, we introduce "cross-expression," which models the degree to which genes coordinate their expression across spatially adjacent cells, avoiding the use of curated databases and cell type labels while controlling for cell-intrinsic processes. RESULTS: We use multiple atlas-scale adult mouse brain datasets (~25 million cells, 695 slices from 52 brains, 8 technologies) to create an integrated, meta-analytic cross-expression network, whose communities are enriched in spatial processes such as synaptic signaling and G protein coupled receptor activity. Highlighting cross-expression's biological utility, our network shows that genes Drd1 and Gpr6, which are individually implicated in Parkinson's disease (PD), are cross-expressed within the striatum, hinting at their joint role in PD pathophysiology. It also recovers ligand-receptor pairs as cross-expressing genes and finds gene combinations that mark anatomical regions, thus complementing cell-cell communication approaches and marker gene-based region annotation, respectively. CONCLUSIONS: We offer a gene-centric perspective to understand spatially coordinated expression between neighboring cells. Our method only requires the gene expression and cell location matrices to find cross-expressing gene pairs. The R package is available at https://github.com/gillislab/CrossExpression .
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.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 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".