Constructing Hypomorphic and Null-suppressed Alleles of Human Essential Genes to Map Genetic Interactions
Bibliographic record
Abstract
The current limitation in mapping all pairwise genetic interactions (GIs) in a model human cell line is that the number of measurements required is an order of magnitude greater than budding yeast, the only organism to-date where all pairwise GIs have been mapped systematically. This problem of scale for a human cell model requires the prioritization of query genes. In yeast, essential genes were found to represent GI hubs, demonstrating that essential genes are a good way to prioritize genes for surveying GIs. However, there is no method of creating human essential gene ‘queries’ without causing the cells to die. My overarching goal is to develop a method for generating essential gene queries in a model human cell line. I constructed hypomorphic alleles for four core essential genes (TUBB, POLR2A, CCT3 and TCP1), validated partial loss-of-function phenotypes, and demonstrated the effectiveness of hypomorphs for exploring GIs in essential genes.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".