Targeted deletion of repeat sequences in the 3’UTR of MDM2 using CRISPR/Cas9
Bibliographic record
Abstract
Mutations in the TP53 tumour suppressor gene are found in over 50% of cancers.This p53 protein is of central importance to prevent cancer progression.The MDM2 oncoprotein is an E3 ubiquitin ligase responsible for negatively regulating p53 to prevent sustained ectopic expression of p53, and adverse consequences for cells.The MDM2 3'UTR is exceptionally long (up to 75% of the 7.5 kb mRNA sequence) and contains many putative cis-acting regulatory elements, including unique repeat sequences predicted to form complex secondary structures.I generated several clonal populations of HCT116 cells heterozygous for a deletion of this region using a tandem sgRNA CRISPR-Cas9 approach.No gross differences in MDM2 protein or mRNA expression were detected.The deletions appeared to be facilitated by regions of homology and cannot readily be explained with the current understanding of DNA repair pathways associated with CRISPR-Cas9 gene editing.
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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 | 0.000 |
| 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) | 0.002 | 0.001 |
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".