File contents ---name: multi-ancestry-prs-agent
description: AI-powered multi-ancestry polygenic risk score calculation and optimization for equitable disease risk prediction across diverse global populations.
license: MIT
metadata:
author: AI Group
version: "1.0.0"
created: "2026-01-20"
compatibility:
system: Python 3.10+
allowed-tools:
run_shell_command
read_file
write_file
keywords:
multi-ancestry-prs-agent
automation
biomedical
measurable_outcome: execute task with >95% success rate.
---"
Multi-Ancestry PRS Agent
The Multi-Ancestry PRS Agent provides AI-optimized polygenic risk score calculation designed to work across diverse ancestral populations. It addresses the critical limitation of European-biased GWAS by integrating trans-ancestry methods, improving risk prediction for underrepresented populations and enabling equitable precision medicine.
When to Use This Skill
When calculating PRS for non-European ancestry individuals.
For developing trans-ancestry risk prediction models.
To reduce PRS bias across ancestral populations.
When integrating multi-ancestry GWAS summary statistics.
For research on PRS portability and equity.
Core Capabilities
Multi-Ancestry PRS : Calculate ancestry-aware polygenic scores.
Trans-Ancestry Optimization : Optimize weights across populations.
Local Ancestry Integration : Account for admixed genomes.
Ensemble Methods : Combine multiple PRS approaches.
Ancestry Calibration : Population-specific score calibration.
Equity Assessment : Evaluate prediction fairness across groups.
Supported Ancestries
Ancestry
Training Data Availability
PRS Performance
European (EUR)
Excellent
High
East Asian (EAS)
Good
Good
South Asian (SAS)
Moderate
Moderate
African (AFR)
Limited
Lower
Hispanic/Latino (AMR)
Limited
Variable
Middle Eastern (MID)
Very Limited
Lower
Multi-Ancestry Methods
Method
Approach
Best For
PRS-CSx
Cross-population shrinkage
Multi-ancestry
PRS-Multi
Multi-population training
Large cohorts
Ensemble
Combined methods
Best overall
Local Ancestry
Ancestry-specific weights
Admixed populations
GPSMult
Integrated multi-trait
Correlated traits
Workflow
Input : Individual genotypes, target ancestry, disease/trait.
Ancestry Inference : Determine genetic ancestry.
Method Selection : Choose optimal PRS approach.
Score Calculation : Compute ancestry-aware PRS.
Calibration : Apply population-specific calibration.
Risk Stratification : Categorize into risk groups.
Output : PRS, percentile, clinical interpretation.
Example Usage
User : "Calculate multi-ancestry coronary artery disease PRS for this admixed individual with African and European ancestry."
Agent Action :
python3 Skills/Precision_Medicine/Multi_Ancestry_PRS_Agent/calc_prs.py \
--genotypes patient_genotypes.vcf.gz \
--ancestry admixed_AFR_EUR \
--local_ancestry lai_segments.bed \
--trait coronary_artery_disease \
--method prs_csx \
--gwas_summary_stats eur_gwas.txt,afr_gwas.txt \
--calibration_cohort 1kg_admixed \
--output prs_results/
Input Requirements
Input
Format
Purpose
Genotypes
VCF/PLINK
Individual variants
Ancestry
Estimated or self-reported
Method selection
GWAS Summary Stats
Multiple ancestries
Score weights
Local Ancestry
LAI segments
Admixture handling
Reference Panel
Multi-ancestry
LD calculation
Output Components
Output
Description
Format
PRS Score
Raw polygenic score
.csv
Percentile
Population-specific ranking
.csv
Risk Category
High/Intermediate/Low
.csv
Ancestry Breakdown
Component scores
.json
Confidence Interval
Score uncertainty
.json
Clinical Interpretation
Risk explanation
.md
Disease-Specific Performance
Disease
Multi-Ancestry AUC
EUR Only AUC
Improvement
CAD
0.75-0.80
0.70-0.85
5-10% in non-EUR
Type 2 Diabetes
0.70-0.75
0.65-0.72
8-12% in AFR
Breast Cancer
0.65-0.72
0.60-0.70
5-8% globally
Alzheimer's
0.70-0.78
0.65-0.75
5-10% in diverse
AI/ML Components
PRS Optimization :
Bayesian shrinkage (PRS-CS)
Cross-population learning
Neural network weight optimization
Ancestry Inference :
Supervised classification
Unsupervised clustering (PCA, ADMIXTURE)
Local ancestry inference (RFMix)
Ensemble Learning :
Stacking multiple PRS methods
Ancestry-stratified weighting
Uncertainty quantification
Clinical Integration
Application
PRS Role
Clinical Action
Primary Prevention
Risk stratification
Screening intensity
Risk Communication
Personalized risk
Lifestyle modification
Treatment Selection
Predicted response
Drug choice
Family Screening
Cascade testing
Genetic counseling
Prerequisites
Python 3.10+
PLINK 2.0
PRSice-2, LDpred2, PRS-CSx
Multi-ancestry reference panels
GWAS summary statistics
Related Skills
PRS_Net_Deep_Learning_Agent - Deep learning PRS
Pharmacogenomics_Agent - Drug-gene interactions
PopEVE_Variant_Predictor_Agent - Variant interpretation
DiagAI_Agent - Clinical integration
Bias and Fairness
Bias Type
Cause
Mitigation
Discovery Bias
EUR-dominated GWAS
Multi-ancestry GWAS
LD Variation
Population-specific LD
Local ancestry adjustment
Allele Frequency
Differing frequencies
Population-specific weights
Effect Size
Heterogeneous effects
Trans-ancestry meta-analysis
Large-Scale Initiatives
Initiative
Focus
Contribution
All of Us
US diversity
1M diverse participants
PAGE
Multi-ethnic GWAS
Discovery in diverse
H3Africa
African genomics
Continental diversity
Mexican Biobank
Latin American
Admixed populations
GBMI
Global Biobank
Multi-ancestry meta-analysis
Special Considerations
Self-Reported Ancestry : May not match genetic ancestry
Admixture : Require local ancestry methods
Population Stratification : Careful covariate adjustment
Clinical Validity : Validate in target population
Health Equity : Consider access disparities
ESC Guidelines Integration (2025)
Recommendation
PRS Role
Evidence Level
CV Risk Assessment
Risk modifier
IIa, B
Statin Decisions
Borderline risk reclassification
IIa, B
Family History Enhancement
Quantify genetic burden
IIa, C
Limitations
Limitation
Impact
Research Needed
AFR Performance
Lower accuracy
More GWAS
Rare Variants
Not captured
WGS integration
Gene-Environment
Not modeled
Interaction studies
Clinical Utility
Limited evidence
Randomized trials
Author
AI Group - Biomedical AI Platform
1 --- 2 name: multi-ancestry-prs-agent 3 description: ---name: multi-ancestry-prs-agent 4 --- 5
6 ---name: multi-ancestry-prs-agent
7 description: AI-powered multi-ancestry polygenic risk score calculation and optimization for equitable disease risk prediction across diverse global populations.
8 license: MIT
9 metadata:
10 author: AI Group
11 version: "1.0.0"
12 created: "2026-01-20"
13 compatibility:
14 - system: Python 3.10+
15 allowed-tools:
16 - run_shell_command
17 - read_file
18 - write_file
19
20 keywords:
21 - multi-ancestry-prs-agent
22 - automation
23 - biomedical
24 measurable_outcome: execute task with >95% success rate.
25 ---"
26
27 # Multi-Ancestry PRS Agent
28
29 The **Multi-Ancestry PRS Agent** provides AI-optimized polygenic risk score calculation designed to work across diverse ancestral populations. It addresses the critical limitation of European-biased GWAS by integrating trans-ancestry methods, improving risk prediction for underrepresented populations and enabling equitable precision medicine.
30
31 ## When to Use This Skill
32
33 * When calculating PRS for non-European ancestry individuals.
34 * For developing trans-ancestry risk prediction models.
35 * To reduce PRS bias across ancestral populations.
36 * When integrating multi-ancestry GWAS summary statistics.
37 * For research on PRS portability and equity.
38
39 ## Core Capabilities
40
41 1. **Multi-Ancestry PRS**: Calculate ancestry-aware polygenic scores.
42
43 2. **Trans-Ancestry Optimization**: Optimize weights across populations.
44
45 3. **Local Ancestry Integration**: Account for admixed genomes.
46
47 4. **Ensemble Methods**: Combine multiple PRS approaches.
48
49 5. **Ancestry Calibration**: Population-specific score calibration.
50
51 6. **Equity Assessment**: Evaluate prediction fairness across groups.
52
53 ## Supported Ancestries
54
55 | Ancestry | Training Data Availability | PRS Performance |
56 |----------|---------------------------|-----------------|
57 | European (EUR) | Excellent | High |
58 | East Asian (EAS) | Good | Good |
59 | South Asian (SAS) | Moderate | Moderate |
60 | African (AFR) | Limited | Lower |
61 | Hispanic/Latino (AMR) | Limited | Variable |
62 | Middle Eastern (MID) | Very Limited | Lower |
63
64 ## Multi-Ancestry Methods
65
66 | Method | Approach | Best For |
67 |--------|----------|----------|
68 | PRS-CSx | Cross-population shrinkage | Multi-ancestry |
69 | PRS-Multi | Multi-population training | Large cohorts |
70 | Ensemble | Combined methods | Best overall |
71 | Local Ancestry | Ancestry-specific weights | Admixed populations |
72 | GPSMult | Integrated multi-trait | Correlated traits |
73
74 ## Workflow
75
76 1. **Input**: Individual genotypes, target ancestry, disease/trait.
77
78 2. **Ancestry Inference**: Determine genetic ancestry.
79
80 3. **Method Selection**: Choose optimal PRS approach.
81
82 4. **Score Calculation**: Compute ancestry-aware PRS.
83
84 5. **Calibration**: Apply population-specific calibration.
85
86 6. **Risk Stratification**: Categorize into risk groups.
87
88 7. **Output**: PRS, percentile, clinical interpretation.
89
90 ## Example Usage
91
92 **User**: "Calculate multi-ancestry coronary artery disease PRS for this admixed individual with African and European ancestry."
93
94 **Agent Action**:
95 ```bash
96 python3 Skills/Precision_Medicine/Multi_Ancestry_PRS_Agent/calc_prs.py \
97 --genotypes patient_genotypes.vcf.gz \
98 --ancestry admixed_AFR_EUR \
99 --local_ancestry lai_segments.bed \
100 --trait coronary_artery_disease \
101 --method prs_csx \
102 --gwas_summary_stats eur_gwas.txt,afr_gwas.txt \
103 --calibration_cohort 1kg_admixed \
104 --output prs_results/
105 ```
106
107 ## Input Requirements
108
109 | Input | Format | Purpose |
110 |-------|--------|---------|
111 | Genotypes | VCF/PLINK | Individual variants |
112 | Ancestry | Estimated or self-reported | Method selection |
113 | GWAS Summary Stats | Multiple ancestries | Score weights |
114 | Local Ancestry | LAI segments | Admixture handling |
115 | Reference Panel | Multi-ancestry | LD calculation |
116
117 ## Output Components
118
119 | Output | Description | Format |
120 |--------|-------------|--------|
121 | PRS Score | Raw polygenic score | .csv |
122 | Percentile | Population-specific ranking | .csv |
123 | Risk Category | High/Intermediate/Low | .csv |
124 | Ancestry Breakdown | Component scores | .json |
125 | Confidence Interval | Score uncertainty | .json |
126 | Clinical Interpretation | Risk explanation | .md |
127
128 ## Disease-Specific Performance
129
130 | Disease | Multi-Ancestry AUC | EUR Only AUC | Improvement |
131 |---------|-------------------|--------------|-------------|
132 | CAD | 0.75-0.80 | 0.70-0.85 | 5-10% in non-EUR |
133 | Type 2 Diabetes | 0.70-0.75 | 0.65-0.72 | 8-12% in AFR |
134 | Breast Cancer | 0.65-0.72 | 0.60-0.70 | 5-8% globally |
135 | Alzheimer's | 0.70-0.78 | 0.65-0.75 | 5-10% in diverse |
136
137 ## AI/ML Components
138
139 **PRS Optimization**:
140 - Bayesian shrinkage (PRS-CS)
141 - Cross-population learning
142 - Neural network weight optimization
143
144 **Ancestry Inference**:
145 - Supervised classification
146 - Unsupervised clustering (PCA, ADMIXTURE)
147 - Local ancestry inference (RFMix)
148
149 **Ensemble Learning**:
150 - Stacking multiple PRS methods
151 - Ancestry-stratified weighting
152 - Uncertainty quantification
153
154 ## Clinical Integration
155
156 | Application | PRS Role | Clinical Action |
157 |-------------|----------|-----------------|
158 | Primary Prevention | Risk stratification | Screening intensity |
159 | Risk Communication | Personalized risk | Lifestyle modification |
160 | Treatment Selection | Predicted response | Drug choice |
161 | Family Screening | Cascade testing | Genetic counseling |
162
163 ## Prerequisites
164
165 * Python 3.10+
166 * PLINK 2.0
167 * PRSice-2, LDpred2, PRS-CSx
168 * Multi-ancestry reference panels
169 * GWAS summary statistics
170
171 ## Related Skills
172
173 * PRS_Net_Deep_Learning_Agent - Deep learning PRS
174 * Pharmacogenomics_Agent - Drug-gene interactions
175 * PopEVE_Variant_Predictor_Agent - Variant interpretation
176 * DiagAI_Agent - Clinical integration
177
178 ## Bias and Fairness
179
180 | Bias Type | Cause | Mitigation |
181 |-----------|-------|------------|
182 | Discovery Bias | EUR-dominated GWAS | Multi-ancestry GWAS |
183 | LD Variation | Population-specific LD | Local ancestry adjustment |
184 | Allele Frequency | Differing frequencies | Population-specific weights |
185 | Effect Size | Heterogeneous effects | Trans-ancestry meta-analysis |
186
187 ## Large-Scale Initiatives
188
189 | Initiative | Focus | Contribution |
190 |------------|-------|--------------|
191 | All of Us | US diversity | 1M diverse participants |
192 | PAGE | Multi-ethnic GWAS | Discovery in diverse |
193 | H3Africa | African genomics | Continental diversity |
194 | Mexican Biobank | Latin American | Admixed populations |
195 | GBMI | Global Biobank | Multi-ancestry meta-analysis |
196
197 ## Special Considerations
198
199 1. **Self-Reported Ancestry**: May not match genetic ancestry
200 2. **Admixture**: Require local ancestry methods
201 3. **Population Stratification**: Careful covariate adjustment
202 4. **Clinical Validity**: Validate in target population
203 5. **Health Equity**: Consider access disparities
204
205 ## ESC Guidelines Integration (2025)
206
207 | Recommendation | PRS Role | Evidence Level |
208 |----------------|----------|----------------|
209 | CV Risk Assessment | Risk modifier | IIa, B |
210 | Statin Decisions | Borderline risk reclassification | IIa, B |
211 | Family History Enhancement | Quantify genetic burden | IIa, C |
212
213 ## Limitations
214
215 | Limitation | Impact | Research Needed |
216 |------------|--------|-----------------|
217 | AFR Performance | Lower accuracy | More GWAS |
218 | Rare Variants | Not captured | WGS integration |
219 | Gene-Environment | Not modeled | Interaction studies |
220 | Clinical Utility | Limited evidence | Randomized trials |
221
222 ## Author
223
224 AI Group - Biomedical AI Platform
majiayu000/claude-skill-registry-data/tree/main/data/multi-ancestry-prs-agent commit bb8b638e54
Frequently asked questions How do I install the Multi Ancestry Prs Agent skill? Run npx skillmds add majiayu000/multi-ancestry-prs-agent in your terminal (requires Node.js), paste this page's agent-chat prompt into Claude, Cursor, or any MCP-connected agent, or download the SKILL.md file and copy it into your agent's skills directory.
What does the Multi Ancestry Prs Agent skill do? ---name: multi-ancestry-prs-agent It is listed under AI & ML on SkillMD.
Is Multi Ancestry Prs Agent safe to use? This skill has not completed SkillMD's automated safety review yet. Capability flags: docs only. SkillMD never runs a skill's scripts for you; review the SKILL.md before installing.
Which AI agents work with Multi Ancestry Prs Agent? This skill is tagged as working with Claude Code, Claude.ai, OpenAI Codex. SKILL.md is an open format, so most agents that read a skills directory can load it too.
Is Multi Ancestry Prs Agent free to use? Yes. Installing skills from SkillMD is free, and the skill stays under its author's original license.
Who published Multi Ancestry Prs Agent? majiayu000 (@majiayu000) published this skill. Their other Agent Skills are listed on their SkillMD profile.