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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

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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

1. Ultra-Sensitive Detection: Detect ctDNA at 0.0001-0.001% VAF levels.

2. Deep Learning Error Suppression: AI-powered sequencing error filtering.

3. Integrated Noise Modeling: Patient-specific background noise estimation.

4. Multi-Feature Integration: Combine mutations, fragmentation, methylation.

5. Zero False Negative Design: Optimized for sensitivity while controlling specificity.

6. 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

1. Input: Deep sequenced cfDNA (>30,000x), tumor WES, matched normal.

2. Preprocessing: UMI deduplication, duplex consensus, quality filtering.

3. Noise Modeling: Patient-specific error profile estimation.

4. Feature Extraction: Mutations, fragments, methylation signals.

5. Deep Learning Inference: MRD-EDGE neural network prediction.

6. Bayesian Integration: Combine features with uncertainty.

7. 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

1. Sample Quality: Requires high-quality cfDNA extraction
2. Sequencing Depth: Deep sequencing essential for sensitivity
3. CHIP Exclusion: Must filter clonal hematopoiesis variants
4. Tumor Heterogeneity: Track clonal and subclonal mutations
5. 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

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