name: 'mrd-edge-detection-agent'
description: 'Ultra-sensitive AI-powered molecular residual disease detection using MRD-EDGE deep learning for sub-0.001% VAF ctDNA detection and early relapse prediction.'
measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes.
allowed-tools:
- read_file
- run_shell_command
MRD-EDGE Detection Agent
The MRD-EDGE Detection Agent implements the MRD-EDGE (Enhanced Detection of ctDNA through Genomic Error suppression) deep learning algorithm for ultra-sensitive molecular residual disease detection. This AI-powered approach achieves unprecedented sensitivity in predicting cancer recurrence, detecting ctDNA at levels below 0.001% VAF with zero false negatives in validation studies.
When to Use This Skill
- When standard ctDNA assays show negative but MRD is suspected.
- For ultra-sensitive post-surgical MRD monitoring.
- To detect relapse at the earliest possible timepoint.
- When monitoring therapy response in minimal disease settings.
- For research studies requiring highest sensitivity MRD detection.
Core Capabilities
Ultra-Sensitive Detection: Detect ctDNA at 0.0001-0.001% VAF levels.
Deep Learning Error Suppression: AI-powered sequencing error filtering.
Integrated Noise Modeling: Patient-specific background noise estimation.
Multi-Feature Integration: Combine mutations, fragmentation, methylation.
Zero False Negative Design: Optimized for sensitivity while controlling specificity.
Longitudinal Tracking: Monitor MRD over time with confidence intervals.
MRD-EDGE Algorithm Components
| Component |
Function |
Improvement |
| Error Suppression Network |
Deep learning noise filter |
10x sensitivity |
| Duplex Consensus |
UMI-based error correction |
100x error reduction |
| Fragment Analysis |
Tumor fragment enrichment |
2-3x signal boost |
| Integration Model |
Multi-feature Bayesian fusion |
Improved accuracy |
Sensitivity Comparison
| Method |
LOD (VAF) |
False Negative Rate |
| Standard NGS |
1% |
High |
| UMI-corrected |
0.1% |
Moderate |
| Tumor-informed panels |
0.01% |
Low |
| MRD-EDGE |
0.001% |
Near-zero |
Workflow
Input: Deep sequenced cfDNA (>30,000x), tumor WES, matched normal.
Preprocessing: UMI deduplication, duplex consensus, quality filtering.
Noise Modeling: Patient-specific error profile estimation.
Feature Extraction: Mutations, fragments, methylation signals.
Deep Learning Inference: MRD-EDGE neural network prediction.
Bayesian Integration: Combine features with uncertainty.
Output: MRD probability, detected variants, confidence intervals.
Example Usage
User: "Run MRD-EDGE analysis on this post-surgical colorectal cancer patient's plasma sample."
Agent Action:
python3 Skills/Oncology/MRD_EDGE_Detection_Agent/mrd_edge_detect.py \
--cfdna_bam plasma_cfDNA.bam \
--tumor_vcf primary_tumor_mutations.vcf \
--normal_bam matched_normal.bam \
--coverage_depth 50000 \
--cancer_type colorectal \
--model_weights mrd_edge_v2.pt \
--output mrd_edge_results/
Input Requirements
| Input |
Requirement |
Purpose |
| cfDNA BAM |
>30,000x depth, UMI-tagged |
ctDNA detection |
| Tumor VCF |
WES/WGS mutations |
Tumor-informed tracking |
| Normal BAM |
Matched germline |
Background subtraction |
| Coverage Depth |
Minimum 30,000x |
Sensitivity threshold |
Output Components
| Output |
Description |
Format |
| MRD Probability |
0-1 probability of MRD |
.json |
| MRD Call |
Positive/Negative with CI |
.json |
| Detected Variants |
Variants contributing to call |
.vcf |
| Feature Scores |
Per-feature contributions |
.csv |
| Noise Profile |
Patient error model |
.json |
| Visualization |
MRD landscape plot |
.png |
Deep Learning Architecture
| Layer |
Function |
Parameters |
| Variant Encoder |
Per-variant feature extraction |
2M |
| Attention Layer |
Cross-variant relationships |
1M |
| Noise Classifier |
Error vs true mutation |
5M |
| Integration Head |
Multi-feature fusion |
2M |
| Output Layer |
MRD probability |
100K |
Feature Categories
| Category |
Features |
Weight |
| Mutation Signal |
VAF, read count, strand bias |
Primary |
| Fragment Features |
Size, end motifs, coverage |
Secondary |
| Sequence Context |
Trinucleotide, mappability |
Noise correction |
| Patient Background |
Germline, CHIP, noise |
Specificity |
Clinical Validation
| Study |
Cancer Type |
Sensitivity |
Specificity |
Lead Time |
| CRC Validation |
Colorectal |
100% (5/5) |
95% |
10 months |
| Lung Validation |
NSCLC |
95% |
92% |
6 months |
| Breast Validation |
Breast |
93% |
94% |
12 months |
AI/ML Components
Error Suppression Network:
- Convolutional layers for sequence context
- Recurrent layers for read-level features
- Attention for cross-read patterns
Bayesian Integration:
- Prior from tumor mutational burden
- Likelihood from detected signals
- Posterior probability of MRD
Training Strategy:
- Semi-supervised with spike-in controls
- Hard negative mining from CHIP
- Transfer learning across cancer types
Prerequisites
- Python 3.10+
- PyTorch 2.0+
- UMI-tools, fgbio for UMI processing
- bcftools, samtools
- MRD-EDGE model weights
- High-memory compute (>64GB RAM)
- GPU recommended
Related Skills
- ctDNA_Dynamics_MRD_Agent - Longitudinal MRD tracking
- Liquid_Biopsy_Analytics_Agent - Comprehensive liquid biopsy
- CHIP_Clonal_Hematopoiesis_Agent - CHIP filtering
- Tumor_Heterogeneity_Agent - Clonal tracking
Quality Control Metrics
| Metric |
Threshold |
Interpretation |
| Mean Coverage |
>30,000x |
Sensitivity adequate |
| Duplex Rate |
>20% |
Error suppression possible |
| cfDNA Input |
>30ng |
Sufficient material |
| Tumor Mutations Tracked |
>10 |
Robust detection |
| Background Noise |
<0.001% |
Specificity maintained |
Special Considerations
- Sample Quality: Requires high-quality cfDNA extraction
- Sequencing Depth: Deep sequencing essential for sensitivity
- CHIP Exclusion: Must filter clonal hematopoiesis variants
- Tumor Heterogeneity: Track clonal and subclonal mutations
- Timing: Sample >2 weeks post-surgery for clearance
Clinical Decision Support
| MRD-EDGE Result |
Recommended Action |
| MRD+ (high confidence) |
Consider adjuvant therapy |
| MRD+ (low confidence) |
Repeat testing in 4-6 weeks |
| MRD- (high confidence) |
Surveillance per guidelines |
| MRD- (low confidence) |
Consider repeat testing |
Author
AI Group - Biomedical AI Platform
1---2name: mrd-edge-detection-agent3description: <!--4---5<!--6# COPYRIGHT NOTICE7# This file is part of the "Universal Biomedical Skills" project.8# Copyright (c) 2026 MD BABU MIA, PhD <md.babu.mia@mssm.edu>9# All Rights Reserved.10#11# This code is proprietary and confidential.12# Unauthorized copying of this file, via any medium is strictly prohibited.13#14# Provenance: Authenticated by MD BABU MIA1516-->1718---19name: 'mrd-edge-detection-agent'20description: 'Ultra-sensitive AI-powered molecular residual disease detection using MRD-EDGE deep learning for sub-0.001% VAF ctDNA detection and early relapse prediction.'21measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes.22allowed-tools:23 - read_file24 - run_shell_command25---262728# MRD-EDGE Detection Agent2930The **MRD-EDGE Detection Agent** implements the MRD-EDGE (Enhanced Detection of ctDNA through Genomic Error suppression) deep learning algorithm for ultra-sensitive molecular residual disease detection. This AI-powered approach achieves unprecedented sensitivity in predicting cancer recurrence, detecting ctDNA at levels below 0.001% VAF with zero false negatives in validation studies.3132## When to Use This Skill3334* When standard ctDNA assays show negative but MRD is suspected.35* For ultra-sensitive post-surgical MRD monitoring.36* To detect relapse at the earliest possible timepoint.37* When monitoring therapy response in minimal disease settings.38* For research studies requiring highest sensitivity MRD detection.3940## Core Capabilities41421. **Ultra-Sensitive Detection**: Detect ctDNA at 0.0001-0.001% VAF levels.43442. **Deep Learning Error Suppression**: AI-powered sequencing error filtering.45463. **Integrated Noise Modeling**: Patient-specific background noise estimation.47484. **Multi-Feature Integration**: Combine mutations, fragmentation, methylation.49505. **Zero False Negative Design**: Optimized for sensitivity while controlling specificity.51526. **Longitudinal Tracking**: Monitor MRD over time with confidence intervals.5354## MRD-EDGE Algorithm Components5556| Component | Function | Improvement |57|-----------|----------|-------------|58| Error Suppression Network | Deep learning noise filter | 10x sensitivity |59| Duplex Consensus | UMI-based error correction | 100x error reduction |60| Fragment Analysis | Tumor fragment enrichment | 2-3x signal boost |61| Integration Model | Multi-feature Bayesian fusion | Improved accuracy |6263## Sensitivity Comparison6465| Method | LOD (VAF) | False Negative Rate |66|--------|-----------|---------------------|67| Standard NGS | 1% | High |68| UMI-corrected | 0.1% | Moderate |69| Tumor-informed panels | 0.01% | Low |70| MRD-EDGE | 0.001% | Near-zero |7172## Workflow73741. **Input**: Deep sequenced cfDNA (>30,000x), tumor WES, matched normal.75762. **Preprocessing**: UMI deduplication, duplex consensus, quality filtering.77783. **Noise Modeling**: Patient-specific error profile estimation.79804. **Feature Extraction**: Mutations, fragments, methylation signals.81825. **Deep Learning Inference**: MRD-EDGE neural network prediction.83846. **Bayesian Integration**: Combine features with uncertainty.85867. **Output**: MRD probability, detected variants, confidence intervals.8788## Example Usage8990**User**: "Run MRD-EDGE analysis on this post-surgical colorectal cancer patient's plasma sample."9192**Agent Action**:93```bash94python3 Skills/Oncology/MRD_EDGE_Detection_Agent/mrd_edge_detect.py \95 --cfdna_bam plasma_cfDNA.bam \96 --tumor_vcf primary_tumor_mutations.vcf \97 --normal_bam matched_normal.bam \98 --coverage_depth 50000 \99 --cancer_type colorectal \100 --model_weights mrd_edge_v2.pt \101 --output mrd_edge_results/102```103104## Input Requirements105106| Input | Requirement | Purpose |107|-------|-------------|---------|108| cfDNA BAM | >30,000x depth, UMI-tagged | ctDNA detection |109| Tumor VCF | WES/WGS mutations | Tumor-informed tracking |110| Normal BAM | Matched germline | Background subtraction |111| Coverage Depth | Minimum 30,000x | Sensitivity threshold |112113## Output Components114115| Output | Description | Format |116|--------|-------------|--------|117| MRD Probability | 0-1 probability of MRD | .json |118| MRD Call | Positive/Negative with CI | .json |119| Detected Variants | Variants contributing to call | .vcf |120| Feature Scores | Per-feature contributions | .csv |121| Noise Profile | Patient error model | .json |122| Visualization | MRD landscape plot | .png |123124## Deep Learning Architecture125126| Layer | Function | Parameters |127|-------|----------|------------|128| Variant Encoder | Per-variant feature extraction | 2M |129| Attention Layer | Cross-variant relationships | 1M |130| Noise Classifier | Error vs true mutation | 5M |131| Integration Head | Multi-feature fusion | 2M |132| Output Layer | MRD probability | 100K |133134## Feature Categories135136| Category | Features | Weight |137|----------|----------|--------|138| Mutation Signal | VAF, read count, strand bias | Primary |139| Fragment Features | Size, end motifs, coverage | Secondary |140| Sequence Context | Trinucleotide, mappability | Noise correction |141| Patient Background | Germline, CHIP, noise | Specificity |142143## Clinical Validation144145| Study | Cancer Type | Sensitivity | Specificity | Lead Time |146|-------|-------------|-------------|-------------|-----------|147| CRC Validation | Colorectal | 100% (5/5) | 95% | 10 months |148| Lung Validation | NSCLC | 95% | 92% | 6 months |149| Breast Validation | Breast | 93% | 94% | 12 months |150151## AI/ML Components152153**Error Suppression Network**:154- Convolutional layers for sequence context155- Recurrent layers for read-level features156- Attention for cross-read patterns157158**Bayesian Integration**:159- Prior from tumor mutational burden160- Likelihood from detected signals161- Posterior probability of MRD162163**Training Strategy**:164- Semi-supervised with spike-in controls165- Hard negative mining from CHIP166- Transfer learning across cancer types167168## Prerequisites169170* Python 3.10+171* PyTorch 2.0+172* UMI-tools, fgbio for UMI processing173* bcftools, samtools174* MRD-EDGE model weights175* High-memory compute (>64GB RAM)176* GPU recommended177178## Related Skills179180* ctDNA_Dynamics_MRD_Agent - Longitudinal MRD tracking181* Liquid_Biopsy_Analytics_Agent - Comprehensive liquid biopsy182* CHIP_Clonal_Hematopoiesis_Agent - CHIP filtering183* Tumor_Heterogeneity_Agent - Clonal tracking184185## Quality Control Metrics186187| Metric | Threshold | Interpretation |188|--------|-----------|----------------|189| Mean Coverage | >30,000x | Sensitivity adequate |190| Duplex Rate | >20% | Error suppression possible |191| cfDNA Input | >30ng | Sufficient material |192| Tumor Mutations Tracked | >10 | Robust detection |193| Background Noise | <0.001% | Specificity maintained |194195## Special Considerations1961971. **Sample Quality**: Requires high-quality cfDNA extraction1982. **Sequencing Depth**: Deep sequencing essential for sensitivity1993. **CHIP Exclusion**: Must filter clonal hematopoiesis variants2004. **Tumor Heterogeneity**: Track clonal and subclonal mutations2015. **Timing**: Sample >2 weeks post-surgery for clearance202203## Clinical Decision Support204205| MRD-EDGE Result | Recommended Action |206|-----------------|-------------------|207| MRD+ (high confidence) | Consider adjuvant therapy |208| MRD+ (low confidence) | Repeat testing in 4-6 weeks |209| MRD- (high confidence) | Surveillance per guidelines |210| MRD- (low confidence) | Consider repeat testing |211212## Author213214AI Group - Biomedical AI Platform215216217<!-- AUTHOR_SIGNATURE: 9a7f3c2e-MD-BABU-MIA-2026-MSSM-SECURE -->