# Multi-Analyte Liquid Biopsy Panel for Early Colorectal Cancer Detection

## Objective
Develop a cost-optimized multi-analyte classifier combining cfDNA methylation patterns and protein biomarkers for early-stage CRC detection from blood samples.

## Background
CRC is the 3rd most common cancer globally (~1.9M cases/year). Early-stage has >90% survival but most cases diagnosed late. Blood-based screening could improve compliance over colonoscopy. No affordable blood test achieves high sensitivity for stage I-II CRC.

## Data Sources
- TCGA-COAD/READ — methylation (450K), RNA-seq, clinical data (~600 samples)
- GEO GSE149282 — cfDNA methylation from CRC patients and controls
- GEO GSE164191 — circulating protein biomarker panels
- GEO GSE48684 — tissue methylation (450K)
- ClinVar/COSMIC — CRC driver mutations

## Methodology
1. Methylation signature discovery from TCGA tissue data
2. cfDNA validation against blood-derived methylation
3. Protein biomarker integration (CEA, CA19-9, SEPT9, TIMP-1, M2-PK)
4. LASSO panel optimization with cost-weighting
5. Ensemble classifier (logistic regression + GBM)
6. Stage-stratified evaluation
7. Cost-effectiveness modeling vs colonoscopy and existing tests

## Success Criteria
- Stage I-II sensitivity >= 70% at specificity >= 95%
- Combined panel >= 5% AUC improvement over single-modality
- Per-test cost < $200
- Cross-validation stability within 5%