Single cell RNA‐seq analysis of hematopoietic cell types in 22q11.2 deletion syndrome reveals significant changes to non‐T cells
Bibliographic record
Abstract
BACKGROUND: 22q11.2 Deletion syndrome is one of the most common inborn errors of immunity. There is a large body of literature supporting alterations to T cells as a result of thymic hypoplasia. Additional studies have supported changes to B cell behavior which have been presumed to be secondary to impaired T cell help. Yet, there remains a significant gap in our understanding of the impact of this syndrome on non-T cells. METHODS: This study utilized a cohort of 46 participants with 22q11.2 deletion syndrome and 18 age and sex-matched controls. 5' single-cell RNAseq was performed to characterize cell populations and altered gene expression. RESULTS: All cell types exhibited RNA expression differences between patients and controls. Across T cells, B cells, NK cells and monocytes, there were no conserved modules either up or down regulated; however, all cell types exhibited differences between controls and patients. Among naïve, memory, and terminal effector CD4 T cells, we observed a number of signatures related to proliferation as manifested by translation initiation and ribosomal component gene expression that were increased in patients. Patients who had had cardiac surgery had altered CD8 T cells with lower naïve CD8 T cells compared to patients who did not have cardiac surgery and increased gene expression in modules defined by oxidative phosphorylation and interferon exposure. CONCLUSIONS: Surprisingly, all cell types examined exhibited differences between patients and controls. Monocytes and NK cells, the cell types least likely to be directly impacted by thymic effects, had unique patterns of gene expression, although both were highly altered in patients. This suggests a widespread impact of the deletion that may be related to direct and indirect effects of reduced gene dosage.
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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 | 0.001 | 0.001 |
| 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".