--- name: 'hrd-analysis-agent' description: 'AI-powered homologous recombination deficiency (HRD) analysis for PARP inhibitor response prediction using genomic scarring signatures and BRCA pathway assessment.' measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes. allowed-tools: - read_file - run_shell_command --- # HRD Analysis Agent The **HRD Analysis Agent** provides comprehensive analysis of homologous recombination deficiency for predicting response to PARP inhibitors and platinum chemotherapy. It integrates genomic scarring signatures (LOH, TAI, LST), BRCA1/2 status, and HRD gene pathway analysis. ## When to Use This Skill * When determining HRD status for PARP inhibitor eligibility. * To calculate genomic instability scores (GIS) from tumor sequencing. * For analyzing BRCA1/2 and HRD gene mutations. * When predicting response to PARP inhibitors or platinum chemotherapy. * To identify "BRCAness" phenotype in BRCA wild-type tumors. ## Core Capabilities 1. **Genomic Scar Scoring**: Calculate LOH, TAI, and LST scores from copy number data. 2. **BRCA Pathway Analysis**: Assess mutations in BRCA1, BRCA2, and 13 other HRD genes. 3. **HRD Classification**: Determine HRD-positive vs. HRD-negative status. 4. **PARP Inhibitor Prediction**: Predict response to olaparib, niraparib, rucaparib, talazoparib. 5. **Platinum Sensitivity**: Predict platinum chemotherapy sensitivity. 6. **Reversion Detection**: Identify BRCA reversion mutations restoring HR function. ## HRD Scoring Components | Score | Definition | Biological Basis | |-------|------------|------------------| | LOH | Loss of heterozygosity regions >15 Mb | Genomic scarring | | TAI | Telomeric allelic imbalance | End-to-end fusions | | LST | Large-scale state transitions | Break-induced repair | | GIS | Combined LOH + TAI + LST | Overall HRD score | **HRD-Positive Threshold**: GIS ≥ 42 (Myriad myChoice) or equivalent ## HRD Gene Panel | Gene | Function | HRD Contribution | |------|----------|------------------| | BRCA1 | HR core component | Major | | BRCA2 | RAD51 loading | Major | | PALB2 | BRCA2 partner | Moderate-Major | | RAD51C/D | HR mediators | Moderate | | ATM | DNA damage sensing | Moderate | | CHEK2 | Cell cycle checkpoint | Moderate | | BARD1 | BRCA1 partner | Moderate | | BRIP1 | Fanconi pathway | Moderate | | CDK12 | Transcription | Variable | | RAD51B | HR mediator | Low-Moderate | ## Workflow 1. **Input**: Copy number segments, somatic mutations, germline variants. 2. **Scar Calculation**: Compute LOH, TAI, LST from segmented CNV data. 3. **Gene Analysis**: Assess pathogenic variants in HRD genes. 4. **Score Integration**: Calculate composite GIS score. 5. **Classification**: Determine HRD status. 6. **Reversion Check**: Screen for reversion mutations. 7. **Output**: HRD score, classification, gene mutations, treatment recommendations. ## Example Usage **User**: "Analyze HRD status for this ovarian cancer patient to guide PARP inhibitor selection." **Agent Action**: ```bash python3 Skills/Oncology/HRD_Analysis_Agent/hrd_analyzer.py \ --cnv_segments tumor_segments.tsv \ --mutations somatic_variants.maf \ --germline germline_variants.vcf \ --tumor_type ovarian \ --purity 0.65 \ --ploidy 2.1 \ --output hrd_report.json ``` ## Commercial HRD Tests | Test | Components | Threshold | FDA Status | |------|------------|-----------|------------| | myChoice CDx | GIS + BRCA | ≥42 or BRCA+ | FDA approved | | FoundationOne | LOH | ≥16% | FDA approved | | SOPHiA DDM HRD | GIS + BRCA | ≥42 or BRCA+ | CE-IVD | ## Clinical Indications **FDA-Approved PARP Inhibitor Indications**: - **Ovarian**: HRD+ or BRCA+ (maintenance, later-line) - **Breast**: gBRCA+ (HER2-, metastatic) - **Pancreatic**: gBRCA+ (maintenance) - **Prostate**: HRR gene mutated (mCRPC) ## Response Prediction | Status | PARP Response | Platinum Response | |--------|---------------|-------------------| | BRCA mutated | Very high | High | | HRD+ / BRCA WT | High | Moderate-High | | HRD- / BRCA WT | Limited | Standard | | Reversion+ | Poor | Poor | ## AI/ML Components **GIS Calculation**: - ASCAT/FACETS for allele-specific CNV - HRDetect algorithm integration - ML refinement of thresholds **Reversion Detection**: - Frameshift restoration analysis - Splice site reversion - Secondary deletion removing stop **Response Prediction**: - Multi-feature model (GIS + genes + expression) - HRDetect signature scoring - Clinical outcome integration ## Resistance Mechanisms | Mechanism | Detection | Implication | |-----------|-----------|-------------| | BRCA reversion | Sequencing | Acquired resistance | | 53BP1 loss | Expression/mutation | Rescued HR | | ABCB1 upregulation | Expression | Drug efflux | | PARP1 loss | Expression | Target loss | ## Prerequisites * Python 3.10+ * ASCAT/FACETS for CNV * HRDetect implementation * Germline/somatic variant callers ## Related Skills * Variant_Interpretation - For BRCA classification * Liquid_Biopsy_Analytics_Agent - For ctDNA HRD monitoring * Pan_Cancer_MultiOmics_Agent - For multi-omic context ## Special Considerations 1. **Tumor Purity**: Low purity affects scar detection 2. **Prior Therapy**: Platinum may select resistant clones 3. **Germline Testing**: Important for family counseling 4. **Reversion Monitoring**: Serial testing recommended ## Author AI Group - Biomedical AI Platform --- Source attribution: FreedomIntelligence Original project: https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills License: MIT License information: https://opensource.org/license/mit Original upstream instructions; downloaded from Mega AI Hub. ## Upstream license notice MIT License Copyright (c) 2026 FridrichMethod Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions: The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software. THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. --- NOTE ON BUNDLED CONTENT This repository aggregates skills from multiple upstream projects (see the README for the source list). Each `skills//` directory may carry its own license inherited from its upstream source. The MIT license above applies to this repository's curation and the scripts/workflows in `/`, `/scripts/`, and `/.github/` — not to the upstream skill content itself. Consult the upstream repository linked in the README and any LICENSE file inside a skill directory before reusing skill content commercially. # Mega AI Hub resource metadata Creator / publisher: FreedomIntelligence Original project: https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills Attribution basis: Exact package in biomedical source index and publisher source table Fields of work: Data & Analytics, Healthcare & Life Sciences Roles: Business Intelligence Analyst, Clinical Research, Data Scientist, Health Informatics, Medical Writer Specialties: API, Testing Tools: Python Country applicability: Country not specified Classification basis: Source catalog labels Instruction SHA-256: ad1a6117716fc39088d36507b88c5ba9adf450698b36a92a01ae3eee4a937685 Metadata reviewed: 2026-10-27 This metadata supersedes earlier Mega AI Hub catalog attribution. Original instruction and supporting files are preserved.