Transcriptomic and Macroscopic Architectures of Multimodal Covariance Network Reveal Molecular–Structural–Functional Co-alterations
Bibliographic record
Abstract
Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions. Owing to lacking an effective approach to quantifying the covarying of structure and functional responses, how the structural-functional circuits interact and how genes encode the relationships, to deepen our knowledge of human cognition and disease, are still unclear. Here, we propose a multimodal covariance network (MCN) construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual. We further explored the potential association between brain-wide gene expression patterns and structural-functional covarying in individuals involved in a gambling task and individuals with major depression disorder (MDD), adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts. MCN analysis showed a replicable cortical structural-functional fine map in healthy individuals, and the expression of cognition- and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences. Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences. In contrast, changes in MCN of MDD patients were enriched for biological processes related to synapse function and neuroinflammation in astrocytes, microglia, and neurons, suggesting its promising application in developing targeted therapies for MDD patients. Collectively, these findings confirmed the correlations of MCN-related differences with brain-wide gene expression patterns, which captured genetically validated structural-functional differences at the cellular level in specific cognitive processes and psychiatric patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".