AI-powered analysis of chromosomal instability (CIN) signatures for cancer prognosis, immunotherapy response prediction, and therapeutic vulnerability identification.
The Chromosomal Instability Agent analyzes CIN signatures to predict cancer prognosis, immunotherapy response, and therapeutic vulnerabilities. It integrates copy number alterations, aneuploidy scores, and CIN-related gene expression for comprehensive genomic instability assessment.
CIN Scoring: Calculate comprehensive CIN scores from copy number data.
Aneuploidy Quantification: Measure arm-level and focal copy number alterations.
CIN Gene Expression: Analyze CIN70 and other transcriptional signatures.
: Assess CIN-immune microenvironment relationships.
Therapeutic Vulnerability: Identify CIN-targeted treatment options.
Prognostic Modeling: Predict outcomes based on CIN signatures.
| Metric | Calculation | Interpretation |
|---|---|---|
| Aneuploidy score | Arm-level alterations | Chromosome-level CIN |
| SCNA burden | Total CNV alterations | Overall instability |
| Weighted GII | Fraction altered genome | Focal vs broad changes |
| CIN70 | 70-gene signature | Transcriptional CIN |
| WGII | Weighted genome instability | Comprehensive score |
Core genes reflecting CIN phenotype:
Input: Copy number data (segments), gene expression, mutation data.
CNV Analysis: Calculate arm-level and focal alterations.
Signature Scoring: Compute CIN70 and other transcriptional signatures.
Integration: Combine DNA and RNA-based CIN metrics.
Immune Analysis: Correlate CIN with TME composition.
Vulnerability Assessment: Identify targetable dependencies.
Output: CIN scores, prognosis, treatment recommendations.
User: "Analyze chromosomal instability in this breast cancer sample and identify treatment vulnerabilities."
Agent Action:
python3 Skills/Oncology/Chromosomal_Instability_Agent/cin_analyzer.py \
--cnv_segments tumor_cnv.tsv \
--expression rnaseq_tpm.tsv \
--mutations somatic.maf \
--tumor_type breast_cancer \
--signatures cin70,cin25 \
--output cin_report/
High CIN Associates With:
Mechanisms:
| Target | Agents | CIN Context |
|---|---|---|
| PARP | Olaparib, etc. | High CIN + HRD |
| ATR | Berzosertib | Replication stress |
| WEE1 | Adavosertib | G2/M dependency |
| CHK1 | Prexasertib | Cell cycle checkpoint |
| KIF11 | Ispinesib | Mitotic dependency |
| Aurora kinases | Alisertib | Mitotic errors |
| CIN Level | Prognosis | ICI Response | Alternative Therapy |
|---|---|---|---|
| Low | Better | Better | Standard care |
| Intermediate | Variable | Variable | Combination therapy |
| High | Poor | Poor | CIN-targeted agents |
| Extreme | Very poor | Immune desert | Chemotherapy |
CIN Score Prediction:
Prognosis Modeling:
Therapeutic Matching:
| Cancer Type | Typical CIN Level | Driver Events |
|---|---|---|
| Ovarian HGSOC | Very high | TP53, BRCA |
| Triple-neg breast | High | TP53, PI3K |
| Colorectal MSS | Moderate-high | APC, TP53 |
| Colorectal MSI | Low | MMR deficiency |
| Thyroid (PTC) | Low | BRAF, RAS |
| Melanoma | Moderate | BRAF, NRAS |
AI Group - Biomedical AI Platform