A GENOME-WIDE CRISPR/CAS9 SCREENING IDENTIFIES GENETIC MODIFIERS OF ΑLPHA SYNUCLEIN AGGREGATES UPTAKE
Bibliographic record
Abstract
Pathological aggregation and propagation of the protein alpha-synuclein (α-syn) in a prion-like fashion underlie the progression of Parkinson’s disease (PD). Understanding how these aggregates propagate from cell to cell thus holds great therapeutic promises. Despite years of efforts, the process of α-syn aggregate uptake, including in dopaminergic neurons that are the primary cell type lost in PD, remains unclear and debated. With this objective in mind, a FACS-based, unbiased genome-wide CRISPR/Cas9 screening was conducted in human retina-pigmented epithelial cells (RPE-1) to identify genes, the invalidation of which modulates the extent of fluorescent α-syn preformed fibrils (PFFs) uptake.
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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".