Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles
Why this work is in the frame
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Bibliographic record
Abstract
Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts,\nwith poor prognosis and limited treatment options. Here, we describe the\nintegrated analysis of somatic mutations, RNA expression, copy number, and DNA\nmethylation by The Cancer Genome Atlas, of a set of predominantly intrahepatic\nCCA cases, and propose a molecular classification scheme. We identified an\nIDH-mutant enriched subtype with distinct molecular\nfeatures including low expression of chromatin modifiers, elevated expression of\nmitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the\nmulti-platform data, we observed that ARID1A exhibited DNA hypermethylation and\ndecreased expression in the IDH-mutant subtype. More broadly,\nwe found that IDH mutations are associated with an expanded\nhistological spectrum of liver tumors with molecular features that stratify with\nCCA. Our studies reveal insights into the molecular pathogenesis and\nheterogeneity of cholangiocarcinoma and provide classification information of\npotential therapeutic significance.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 it