Defining the extent of gene function using ROC curvature
Bibliographic record
Abstract
MOTIVATION: Interactions between proteins help us understand how genes are functionally related and how they contribute to phenotypes. Experiments provide imperfect 'ground truth' information about a small subset of potential interactions in a specific biological context, which can then be extended to the whole genome across different contexts, such as conditions, tissues or species, through machine learning methods. However, evaluating the performance of these methods remains a critical challenge. Here, we propose to evaluate the generalizability of gene characterizations through the shape of performance curves. RESULTS: We identify Functional Equivalence Classes (FECs), subsets of annotated and unannotated genes that jointly drive performance, by assessing the presence of straight lines in ROC curves built from gene-centric prediction tasks, such as function or interaction predictions. FECs are widespread across data types and methods, they can be used to evaluate the extent and context-specificity of functional annotations in a data-driven manner. For example, FECs suggest that B cell markers can be decomposed into shared primary markers (10-50 genes), and tissue-specific secondary markers (100-500 genes). In addition, FECs suggest the existence of functional modules that span a wide range of the genome, with marker sets spanning at most 5% of the genome and data-driven extensions of Gene Ontology sets spanning up to 40% of the genome. Simple to assess visually and statistically, the identification of FECs in performance curves paves the way for novel functional characterization and increased robustness in the definition of functional gene sets. AVAILABILITY AND IMPLEMENTATION: Code for analyses and figures is available at https://github.com/yexilein/pyroc. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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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 | 0.000 | 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) | 0.000 | 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".