Genomic Loci of Radiation-induced Lung Disease in a Mouse Model: Refinement and Candidate Gene Analysis
Bibliographic record
Abstract
Susceptibility to radiation-induced lung disease differs among people and among inbred strains of mice; C3H/HeJ mice develop early onset distress from pneumonitis and C57BL/6J mice present later onset pneumonitis with fibrosis. Previous studies revealed C3H/HeJ alleles at a 28 Mb locus on chromosome 2 to be linked to early onset distress and at an 18 Mb locus on chromosome 17 (called Radpf1 for radiation-induced pulmonary fibrosis-1) to decrease fibrosis in whole-thorax irradiated mice. To potentially reduce these genomic intervals, parental chr17-subcongenic mice with 0.71 Mb of C3H/HeJ alleles, and chr 2-congenic mice with region-spanning C3H/HeJ alleles from 95 to 123 Mb, and four lines of subcongenic mice received 16 Gy whole thorax irradiation and were assessed for onset of respiratory distress and histological lung disease at distress. One hundred percent of irradiated C3H/HeJ and C57BL/6J mice exhibited respiratory distress from pneumonitis and pneumonitis with fibrosis (6.8% of lung), respectively, while 18/19 chr17-subcongenic mice survived to 25 weeks post-treatment without symptoms of distress and with significantly decreased radiation-induced pulmonary fibrosis (0.3% of lung, P = 0.002). Of the chr2-subcongenics, mice of one line, which we refer to as Pneum1 (pneumonitis one), succumbed at an average of 20.2 ± 1.1 weeks postirradiation in females and 26.3 ± 1.2 weeks in males (P > 0.22 vs. congenic mice), reducing this locus to 5.6 Mb. Bioinformatic analyses revealed 114 candidate genes within these reduced intervals, with effects on pathways including on immune pathways. Mapping refined genetic susceptibility to radiation-induced lung disease in mice.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| 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".