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Meta-Layer Experiments

This directory contains documentation for experiments conducted on the meta-layer architecture for splice site prediction.


Experiment Index

ID Name Status Outcome Date
001 Canonical Classification ✅ Completed Partial Success Dec 2025
002 Paired Delta Prediction ✅ Completed r=0.38 (insufficient) Dec 2025
003 Binary Classification (Multi-Step Step 1) ✅ Completed AUC=0.61, F1=0.53 Dec 2025
004 Validated Delta (Single-Pass) ✅ Completed r=0.41 (best!) Dec 2025

Experiment Categories

Classification-Based Approaches

  • 001_canonical_classification: Train on GTF labels, evaluate on SpliceVarDB (FAILED for variants)
  • 003_binary_classification: Multi-Step Step 1 - "Is this variant splice-altering?"

Delta-Based Approaches

  • 002_delta_prediction: Paired (Siamese) prediction (r=0.38)
  • 004_validated_delta: Single-pass with validated targets (r=0.41) - BEST

Directory Structure

Each experiment follows this structure:

NNN_experiment_name/
├── README.md           # Overview, hypothesis, setup, results summary
├── RESULTS.md          # Detailed numerical results (optional)
├── ANALYSIS.md         # In-depth analysis (optional)
├── LESSONS_LEARNED.md  # Key insights and recommendations (optional)
└── (optional)
    ├── config.yaml     # Experiment configuration
    └── figures/        # Plots and visualizations

Key Metrics

For Classification Experiments

  • Accuracy: Overall classification accuracy
  • AP (Average Precision): Per-class ranking quality
  • PR-AUC: Area under precision-recall curve

For Delta Prediction Experiments

  • Pearson r: Correlation with true deltas
  • Detection Rate: % of splice-altering variants detected
  • Mean |Δ|: Average absolute delta score

Quick Reference

Current Best Results

Task Best Model Metric Value
Classification Meta-Layer (001) Accuracy 99.11%
Variant Detection Validated Delta (004) Correlation r=0.41
Binary Classification Multi-Step (003) AUC 0.61

Key Findings

  1. Classification ≠ Detection: High classification accuracy doesn't translate to variant detection
  2. Training objective matters: Must train for the evaluation task
  3. Target quality matters: Learning from potentially wrong base model deltas limits paired prediction
  4. Validated targets work better: SpliceVarDB filtering improves correlation from r=0.38 to r=0.41
  5. Binary classification is learnable: AUC=0.61 > random, but F1=0.53 needs improvement (>0.7)

How to Add a New Experiment

  1. Create directory: NNN_experiment_name/
  2. Copy template from existing experiment
  3. Update README.md with hypothesis and setup
  4. Run experiment, record results
  5. Analyze and document insights
  6. Update this index

  • ARCHITECTURE.md - Meta-layer architecture
  • LABELING_STRATEGY.md - Labeling approaches (planned)
  • methods/ - Methodology documentation