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Hrd Analysis Agent · FreedomIntelligence | DecimalAI

Hrd Analysis Agent

SkillScore91Maintained

hrd-analysis-agent

AI-powered homologous recombination deficiency (HRD) analysis for PARP inhibitor response prediction using genomic scarring signatures and BRCA pathway assessment.

scienceby FreedomIntelligence

Links this skill to your agents and keeps it current with the author’s updates.

Automatic

Clinical / Healthcare pack

1 · One-time — install the CLI (docs ↗)

pip install decimalai

2 · Get the skill — writes .claude/skills/hrd-analysis-agent/SKILL.md

decimalai skills pull hrd-analysis-agent --out .claude/skills/

No CLI? Get the same file — curl · raw file

curl -fsSL --create-dirs -o .claude/skills/hrd-analysis-agent/SKILL.md https://app.decimal.ai/s/hrd-analysis-agent/SKILL.md

Raw file: /s/hrd-analysis-agent/SKILL.md ↗ · machine-readable summary at /s/hrd-analysis-agent.json ↗

In productionGlobal

how this skill behaves on real traffic · last 30 days

No production data for this skill yet — usage numbers appear here once agents start running it.

Anonymized aggregate across every org using this skill — proof from real production use, not a demo.

Does this skill help? · Benchmark: with vs. withoutsign in to run this on your agents

22 test cases from the publisher’s eval.yaml · each run twice on gemini-3.6-flash — with the skill injected, then without · last run 51d ago

—+73% tokens0% turns91% of whole cases pass with skill (20/22)

Test case	Without → With	Effect	Δ tokens	Δ turns
case-03	✗→✓	▲ Improved	9%	0%
case-05	✗→✓	▲ Improved	46%	0%
case-07	✗→✓	▲ Improved	66%	0%
case-14	✗→✓	▲ Improved	72%	0%
case-18	✗→✓	▲ Improved	7%	0%

Showing 5 of 22 cases

SkillSafety

✓ 3 of 3 passed

Code scan15 of 15 checks clean

0 critical · 0 warning · 0 info — scanner v4 — 8/1/2026

live_secretremote_code_executionreverse_shelldata_exfiltrationssrf_metadataagent_snoopinganti_refusaldestructive_commandsobfuscated_unicodeunicode_homoglyphopaque_blobsuspicious_urltool_overreachtrigger_abuseprompt_injection_phrasing

IntentSafe

LLM judge · does the skill do what it claims

ContentClean

LLM judge · policy & harmful-content review

Source

Imported

FreedomIntelligence / OpenClaw-Medical-Skills

skills/hrd-analysis-agent/SKILL.md

View on GitHub ↗

Imported 8/1/2026Version v2

Skill contents

SKILL.md

<!--

COPYRIGHT NOTICE

This file is part of the "Universal Biomedical Skills" project.

Copyright (c) 2026 MD BABU MIA, PhD <md.babu.mia@mssm.edu>

All Rights Reserved.

This code is proprietary and confidential.

Unauthorized copying of this file, via any medium is strictly prohibited.

Provenance: Authenticated by MD BABU MIA

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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

Genomic Scar Scoring: Calculate LOH, TAI, and LST scores from copy number data.

BRCA Pathway Analysis: Assess mutations in BRCA1, BRCA2, and 13 other HRD genes.

HRD Classification: Determine HRD-positive vs. HRD-negative status.

PARP Inhibitor Prediction: Predict response to olaparib, niraparib, rucaparib, talazoparib.

Platinum Sensitivity: Predict platinum chemotherapy sensitivity.

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

Input: Copy number segments, somatic mutations, germline variants.

Scar Calculation: Compute LOH, TAI, LST from segmented CNV data.

Gene Analysis: Assess pathogenic variants in HRD genes.

Score Integration: Calculate composite GIS score.

Classification: Determine HRD status.

Reversion Check: Screen for reversion mutations.

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

Tumor Purity: Low purity affects scar detection
Prior Therapy: Platinum may select resistant clones
Germline Testing: Important for family counseling
Reversion Monitoring: Serial testing recommended

Author

AI Group - Biomedical AI Platform

Illustrative Want to see what hrd-analysis-agent would put in front of your model? Preview the rendered body and check its trigger phrases — no LLM call, no signup.

Latest benchmark · publisher runVerified

8/2/2026, 17:42 UTC · 22 cases

Measured on 21 comparable cases — below the 22 needed to publish a lift, so this result is shown here but not on the registry card or leaderboard.

Lift

+23%

91% vs 68%

Agent turns

1.0 vs 1.0

Tokens

+73%

2,778.29 vs 1,607.48

fail → pass · 5pass → pass · 15fail → fail · 2

Per-case results (22)

Case	Status	Duration (ms)			Turns			Tokens			Tool calls
Case	Status	Without	With	Δ	Without	With	Δ	Without	With	Δ	Without	With	Δ
case-06 In an expanded HRD pathway gene panel assessment, a patient tests positive for a pathogenic loss-of-function variant in PALB2. What is PALB2's primary cellular function in homologous recombination and what is its level of contribution to HRD?	pass→pass	10,247	4,592	-55%	1	1	0%	1,941	2,240	+15%	0	0	—
case-15 In genomic scar signature calculations, how is Telomeric Allelic Imbalance (TAI) defined, and what is its underlying biological cause?	fail→fail	11,979	9,361	-22%	1	1	0%	2,138	3,140	+47%	0	0	—
case-01 We are establishing a clinical pipeline for ovarian cancer homologous recombination deficiency (HRD) classification based on myChoice CDx standards. A tumor sample yields an LOH score of 15, a TAI score of 14, and an LST score of 14, with no pathogenic BRCA1/2 mutations detected. Should this tumor be classified as HRD-positive or HRD-negative based on the standard composite Genomic Instability Score threshold?	pass→pass	6,481	4,807	-26%	1	1	0%	1,305	2,389	+83%	0	0	—
case-02 An analyst is evaluating a genomic profiling report from FoundationOne CDx for a patient with high-grade serous ovarian carcinoma. The report shows BRCA1/2 wild-type status, but the percentage of genomic loss of heterozygosity (LOH) is reported as 18%. Should this patient be considered HRD-positive for PARP inhibitor sensitivity under FoundationOne criteria?	pass→pass	7,631	6,121	-20%	1	1	0%	1,442	2,730	+89%	0	0	—
case-03 Write the command line invocation to run the automated HRD analysis workflow script on an ovarian cancer sample with copy number segments in 'tumor_segments.tsv', somatic mutations in 'somatic_variants.maf', germline variants in 'germline_variants.vcf', tumor purity of 0.65, ploidy of 2.1, saving output to 'hrd_report.json'. What is the exact script filename to invoke?	fail→pass	21,101	3,685	-83%	1	1	0%	1,987	2,168	+9%	0	0	—
case-04 A patient with BRCA1-mutated recurrent ovarian cancer was previously treated with olaparib and experienced disease progression. Subsequent liquid biopsy sequencing revealed a secondary in-frame insertion that restores the open reading frame of BRCA1. How does this reversion mutation impact the predicted response to subsequent PARP inhibitor or platinum chemotherapy treatment?	pass→pass	8,596	10,617	+24%	1	1	0%	1,501	3,432	+129%	0	0	—
case-05 When calculating the Genomic Instability Score (GIS) for HRD assessment, what specific genomic structural alteration does Large-Scale State Transitions (LST) measure, and what is its underlying biological mechanism?	fail→pass	10,289	7,407	-28%	1	1	0%	1,888	2,754	+46%	0	0	—
case-07 A genetic testing panel identifies a truncating mutation in RAD51C in a patient with triple-negative breast cancer. How is RAD51C's contribution to homologous recombination deficiency categorized in HRD risk scoring panels?	fail→pass	11,149	10,265	-8%	1	1	0%	1,963	3,258	+66%	0	0	—
case-08 A patient with high-grade serous ovarian cancer tests wild-type for somatic and germline BRCA1/2 mutations, but receives a Genomic Instability Score (GIS) of 54. What is the predicted clinical response level to PARP inhibitor therapy for this patient?	pass→pass	7,648	5,603	-27%	1	1	0%	1,357	2,536	+87%	0	0	—
case-09 A patient diagnosed with metastatic breast cancer harbors a germline pathogenic BRCA2 mutation. What is the expected efficacy level for platinum-based chemotherapy in this patient profile?	pass→pass	8,290	5,609	-32%	1	1	0%	1,445	2,432	+68%	0	0	—
case-10 What specific biomarker criteria qualify patients with metastatic castration-resistant prostate cancer (mCRPC) for FDA-approved PARP inhibitor therapy?	pass→pass	11,069	10,545	-5%	1	1	0%	2,396	3,588	+50%	0	0	—
case-11 What specific biomarker status is required for FDA-approved PARP inhibitor maintenance therapy in patients with pancreatic adenocarcinoma?	pass→pass	4,870	5,260	+8%	1	1	0%	918	2,404	+162%	0	0	—
case-12 During longitudinal monitoring of a PARP inhibitor-resistant tumor, genomic profiling reveals loss of TP53BP1 (53BP1). What is the molecular mechanism by which 53BP1 loss confers resistance to PARP inhibitors?	pass→pass	10,484	10,261	-2%	1	1	0%	1,854	3,300	+78%	0	0	—
case-13 A tumor biopsy taken after PARP inhibitor relapse exhibits marked upregulation of the ABCB1 gene. What drug resistance mechanism does ABCB1 over-expression represent?	pass→pass	5,156	6,799	+32%	1	1	0%	934	2,590	+177%	0	0	—
case-14 A European oncology department is employing the SOPHiA DDM HRD solution for ovarian cancer stratification. What combined Genomic Instability Score threshold or biomarker finding determines an HRD-positive result under this assay protocol?	fail→pass	8,678	7,293	-16%	1	1	0%	1,644	2,828	+72%	0	0	—
case-16 What is the specific minimum genomic segment size requirement used when calculating Loss of Heterozygosity (LOH) score as part of genomic scar analysis?	pass→pass	6,312	3,833	-39%	1	1	0%	1,011	2,039	+102%	0	0	—
case-17 A molecular tumor board is reviewing an ATM frameshift mutation found in a prostate cancer specimen. What primary molecular function does ATM perform in double-strand break repair, and what is its HRD contribution level?	pass→pass	11,347	5,178	-54%	1	1	0%	1,989	2,358	+19%	0	0	—
case-18 When interpreting a somatic CHEK2 loss-of-function variant on an HRD gene panel, what is CHEK2's primary cellular role and its assigned contribution weight in HRD scoring?	fail→pass	10,775	3,552	-67%	1	1	0%	1,886	2,018	+7%	0	0	—
case-19 A pathologist notes that a primary ovarian resection specimen submitted for genomic scar scoring has an estimated tumor purity of 15%. How does low tumor purity affect the assessment of genomic scar parameters (LOH, TAI, LST)?	pass→pass	13,442	12,699	-6%	1	1	0%	2,314	3,551	+53%	0	0	—
case-20 A somatic panel report for a non-small cell lung cancer patient indicates 14 nonsynonymous mutations across a 1.2 megabase target region. Calculate the Tumor Mutation Burden (TMB) in mutations per megabase (mut/Mb) and classify whether it meets the standard high-TMB threshold (≥10 mut/Mb) for pembrolizumab eligibility.	pass→pass	5,886	4,297	-27%	1	1	0%	1,225	2,329	+90%	0	0	—
case-21 A colorectal cancer specimen was evaluated for microsatellite instability across five consensus mononucleotide repeat markers (BAT25, BAT26, NR21, NR24, MONO27). Three of the five markers show allele length alterations compared to paired normal DNA. Determine the MSI classification status.	pass→pass	5,456	5,071	-7%	1	1	0%	1,109	2,463	+122%	0	0	—
case-22 A patient undergoing germline testing yields a novel missense variant in TP53 (p.R273H). Population databases show an allele frequency of 0.00001 (PM2), functional assays demonstrate loss of transactivation (PS3), and multiple computational algorithms predict pathogenicity (PP3). According to ACMG/AMP tier guidelines, what is the variant classification?	fail→fail	7,039	11,974	+70%	1	1	0%	1,497	3,965	+165%	0	0	—

These cases were also screened by the skill’s intent / safety pass.See the Trust review ↗Reproduce this benchmark in Colab ↗

How this skill was measured

DecimalAI ran this skill against gemini-3.6-flash twice over the same eval suite — once with the skill loaded and once without — and compared the two runs case by case. 22 cases were attempted, and 21 counted toward the lift figure. The other 1 produced results that are not comparable between the two arms, so they are excluded from the headline rather than averaged into it. The headline lift of +23 percentage points is the difference between those two pass rates over the 21 comparable cases.

Model measured: gemini-3.6-flash
Graded by: gemini-3.6-flash
Grading method: judged
Verification: verified
Pass rate without the skill: 68.2%
Pass rate with the skill: 90.9%
Cases attempted: 22
Cases counted toward lift: 21
Cases that regressed: 0
Skill version measured: v2
Run completed: 8/2/2026, 17:42 UTC

Measured example — same prompt, with vs. without the skill · from the benchmark run · case case-05

Prompt

When calculating the Genomic Instability Score (GIS) for HRD assessment, what specific genomic structural alteration does Large-Scale State Transitions (LST) measure, and what is its underlying biological mechanism?

Without the skill loaded, the model failed this case. With it loaded, the same prompt on the same model passed. This is one improved case from the latest verified run; every case, including any that regressed, is in the table above.

Show both answers

SkillScore blends 4 signals1 of 4 complete

BenchmarkPass rate WITH skill on a verified run91

Live evalNeeds ≥10 evaluated traces in 30 days

AI ratingNeeds ≥10 rated traces

AdoptionNeeds ≥10 serves across ≥2 orgs in 30 days

Efficiency · separate axis (at equal correctness)+0% turns+78% tokens

Shown for transparency; not credited unless a verified run shows no correctness regression.

Backed by 1 of 4 signals — each added signal makes the score more robust.

Verified on gemini-3.6-flash · re-tested 50 days ago

Model	Method	Date	Lift
gemini-3.6-flash	verified	7/26/2026	+5%

Other measured skills in the registry, with their headline benchmark lift.