CRISPR-SID: Identifying EZH2 as a druggable target for desmoid tumors via in vivo dependency mapping
Bibliographic record
Abstract
Significance CRISPR-SID was established in the diploid frog Xenopus tropicalis for in vivo elucidation of cancer cell vulnerabilities. CRISPR-SID uses deep-learning predictions and binomial theory to identify genes under positive or negative selection during autochthonous tumor development. Using CRISPR-SID in a genetic model for desmoid tumors, treatment-recalcitrant mesenchymal tumors driven by hyperactivation of the Wnt signaling pathway, we identified EZH2 and SUZ12 , both encoding critical components of the polycomb repressive complex 2, as dependency genes for desmoid tumors. Finally, we demonstrate the promise of EZH2 inhibition as a therapeutic strategy for desmoid tumors. With the simplicity of CRISPR sgRNA multiplexing in Xenopus embryos, the CRISPR-SID method may be applicable to reveal vulnerabilities in other tumor types.
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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 | 0.001 | 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".