Single-nuclei transcriptomics of schizophrenia prefrontal cortex primarily implicates neuronal subtypes
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Transcriptomic studies of bulk neural tissue homogenates from persons with schizophrenia and controls have identified differentially expressed genes in multiple brain regions. However, the brain’s heterogeneous nature prevents identification of relevant cell types. This study analyzed single-nuclei transcriptomics of ~275,000 nuclei from frozen human postmortem dorsolateral prefrontal cortex samples from males with schizophrenia (n = 12) and controls (n = 14). 4,766 differential expression events were identified in 2,994 unique genes in 16 of 20 transcriptomically-distinct cell populations. ~96% of differentially expressed genes occurred in five neuronal cell types, and differentially expressed genes were enriched for genes associated with schizophrenia and bipolar GWAS loci. Downstream analyses identified cluster-specific enriched gene ontologies, KEGG pathways, and canonical pathways. Additionally, microRNAs and transcription factors with overrepresented neuronal cell type-specific targets were identified. These results expand our knowledge of disrupted gene expression in specific cell types and permit new insight into the pathophysiology of schizophrenia.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 it