Uncertainty-aware ensemble of foundation models differentiates glioblastoma from its mimics
Bibliographic record
Abstract
Accurate pathological diagnosis is crucial in guiding personalized treatments for patients with central nervous system cancers. Distinguishing glioblastoma and primary central nervous system lymphoma is particularly challenging due to their overlapping pathology features, despite the distinct treatments required. To address this challenge, we establish the Pathology Image Characterization Tool with Uncertainty-aware Rapid Evaluations (PICTURE) system using 2141 pathology slides collected worldwide. PICTURE employs Bayesian inference, deep ensemble, and normalizing flow to account for the uncertainties in its predictions and training set labels. PICTURE accurately diagnoses glioblastoma and primary central nervous system lymphoma with an area under the receiver operating characteristic curve (AUROC) of 0.989, with the results validated in five independent cohorts (AUROC = 0.924-0.996). In addition, PICTURE identifies samples belonging to 67 types of rare central nervous system cancers that are neither gliomas nor lymphomas. Our approaches provide a generalizable framework for differentiating pathological mimics and enable rapid diagnoses for central nervous system cancer patients. Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".