Detecting Differentially Variable MicroRNAs via Model-Based Clustering
Bibliographic record
Abstract
Identifying differentially variable (DV) genomic probes is becoming a new approach to detect novel genomic risk factors for complex human diseases. The <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"> <mml:mi>F</mml:mi> </mml:math> test is the standard equal-variance test in statistics. For high-throughput genomic data, the probe-wise <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"> <mml:mi>F</mml:mi> </mml:math> test has been successfully used to detect biologically relevant DNA methylation marks that have different variances between two groups of subjects (e.g., cases versus controls). In addition to DNA methylation, microRNA (miRNA) is another important mechanism of epigenetics. However, to the best of our knowledge, no studies have identified DV miRNAs. In this article, we proposed a novel model-based clustering method to improve the power of the probe-wise <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"> <mml:mi>F</mml:mi> </mml:math> test to detect DV miRNAs. We imposed special structures on covariance matrices for each cluster of miRNAs based on the prior information about the relationship between variances in cases and controls and about the independence among them. Simulation studies showed that the proposed method seems promising in detecting DV probes. Based on two real datasets about human hepatocellular carcinoma (HCC), we identified 7 DV-only miRNAs (hsa-miR-1826, hsa-miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR-99b) using the proposed method, one (hsa-miR-1826) of which has not yet been reported to be related to HCC in the literature.
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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".