Precision Medicine Patient Stratification

Transform patient genomic and clinical profiles into actionable risk stratification, treatment recommendations, and personalized therapeutic strategies.

KEY PRINCIPLES

:

Report-first

- Create report file FIRST, then populate progressively

Disease-specific logic

- Cancer vs metabolic vs rare disease pipelines diverge at Phase 3

Multi-level integration

- Germline + somatic + expression + clinical data layers

Evidence-graded

- Every finding has an evidence tier (T1-T4)

Quantitative output

- Precision Medicine Risk Score (0-100)

Source-referenced

- Every statement cites the tool/database source

English-first queries

- Always use English terms in tool calls

Reference files

(same directory):

TOOLS_REFERENCE.md

- Tool parameters, response formats, phase-by-phase tool lists

SCORING_REFERENCE.md

- Scoring matrices, risk tiers, pathogenicity tables, PGx tables

REPORT_TEMPLATE.md

- Output report template, treatment algorithms, completeness requirements

EXAMPLES.md

- Six worked examples (cancer, metabolic, NSCLC, CVD, rare, neuro)

QUICK_START.md

- Sample prompts and output summary

When to Use

Apply when user asks about patient risk stratification, treatment selection, prognosis prediction, or personalized therapeutic strategy for any disease with genomic/clinical data.

NOT for

(use other skills instead):

Single variant interpretation ->

tooluniverse-variant-interpretation

Immunotherapy-specific prediction ->

tooluniverse-immunotherapy-response-prediction

Drug safety profiling only ->

tooluniverse-adverse-event-detection

Target validation ->

tooluniverse-drug-target-validation

Clinical trial search only ->

tooluniverse-clinical-trial-matching

Drug-drug interaction only ->

tooluniverse-drug-drug-interaction

PRS calculation only ->

tooluniverse-polygenic-risk-score

Input Parsing

Required

Disease/condition

Free-text disease name

At least one of

Germline variants, somatic mutations, gene list, or clinical biomarkers

Optional (improves stratification)

Age, sex, ethnicity, disease stage, comorbidities, prior treatments, family history

Current medications (for DDI and PGx), stratification goal

Disease Type Classification

Classify into one category (determines Phase 3 routing):

Category

Examples

CANCER

Breast, lung, colorectal, melanoma

METABOLIC

Type 2 diabetes, obesity, NAFLD

CARDIOVASCULAR

CAD, heart failure, AF

NEUROLOGICAL

Alzheimer, Parkinson, epilepsy

RARE/MONOGENIC

Marfan, CF, sickle cell, Huntington

AUTOIMMUNE

RA, lupus, MS, Crohn's

Critical Tool Parameter Notes

See

TOOLS_REFERENCE.md

for full details. Key gotchas:

MyGene_query_genes

param is

query

(NOT

q

)

EnsemblVEP_annotate_rsid

param is

variant_id

(NOT

rsid

)

ensembl_lookup_gene

REQUIRES

species='homo_sapiens'

DrugBank tools

ALL require 4 params:

query

,

case_sensitive

,

exact_match

,

limit

cBioPortal_get_mutations

:

gene_list

is a STRING (space-separated), not array

PubMed_search_articles

Returns a plain list of dicts, NOT

{articles: [...]}

fda_pharmacogenomic_biomarkers

Use

limit=1000

for all results

gnomAD

May return "Service overloaded" - skip gracefully

OpenTargets

Always nested

{data: {entity: {field: ...}}}

structure

Workflow Overview

Phase 1: Disease Disambiguation & Profile Standardization

Phase 2: Genetic Risk Assessment

Phase 3: Disease-Specific Molecular Stratification (routes by disease type)

Phase 4: Pharmacogenomic Profiling

Phase 5: Comorbidity & Drug Interaction Risk

Phase 6: Molecular Pathway Analysis

Phase 7: Clinical Evidence & Guidelines

Phase 8: Clinical Trial Matching

Phase 9: Integrated Scoring & Recommendations

Phase 1: Disease Disambiguation & Profile Standardization

Resolve disease to EFO ID

using

OpenTargets_get_disease_id_description_by_name

Classify disease type

(CANCER/METABOLIC/CVD/NEUROLOGICAL/RARE/AUTOIMMUNE)

Parse genomic data

into structured format (gene, variant, type)

Resolve gene IDs

using

MyGene_query_genes

to get Ensembl/Entrez IDs

Phase 2: Genetic Risk Assessment

Germline variant pathogenicity

:

clinvar_search_variants

,

EnsemblVEP_annotate_rsid

/

_hgvs

Gene-disease association

:

OpenTargets_target_disease_evidence

GWAS polygenic risk

:

gwas_get_associations_for_trait

,

OpenTargets_search_gwas_studies_by_disease

Population frequency

:

gnomad_get_variant

Gene constraint

:

gnomad_get_gene_constraints

(pLI, LOEUF scores)

Scoring: See

SCORING_REFERENCE.md

for genetic risk score component (0-35 points).

Phase 3: Disease-Specific Molecular Stratification

CANCER PATH

Molecular subtyping

:

cBioPortal_get_mutations

,

HPA_get_cancer_prognostics_by_gene

TMB/MSI/HRD

:

fda_pharmacogenomic_biomarkers

for FDA cutoffs

Prognostic stratification

Combine stage + molecular features

METABOLIC PATH

Genetic risk integration

:

GWAS_search_associations_by_gene

,

OpenTargets_target_disease_evidence

Complication risk

Based on HbA1c, duration, existing complications

CVD PATH

FH gene check

:

clinvar_search_variants

for LDLR, APOB, PCSK9

Statin PGx

:

PharmGKB_get_clinical_annotations

for SLCO1B1

RARE DISEASE PATH

Causal variant identification

:

clinvar_search_variants

Genotype-phenotype

:

UniProt_get_disease_variants_by_accession

Scoring: See

SCORING_REFERENCE.md

for disease-specific tables.

Phase 4: Pharmacogenomic Profiling

Drug-metabolizing enzymes

:

PharmGKB_get_clinical_annotations

,

PharmGKB_get_dosing_guidelines

FDA PGx biomarkers

:

fda_pharmacogenomic_biomarkers

(use

limit=1000

)

Treatment-specific PGx

:

PharmGKB_get_drug_details

Scoring: See

SCORING_REFERENCE.md

for PGx risk score (0-10 points).

Phase 5: Comorbidity & Drug Interaction Risk

Disease overlap

:

OpenTargets_get_associated_targets_by_disease_efoId

DDI check

:

drugbank_get_drug_interactions_by_drug_name_or_id

,

FDA_get_drug_interactions_by_drug_name

PGx-amplified DDI

If PM genotype + CYP inhibitor, flag compounded risk

Phase 6: Molecular Pathway Analysis

Pathway enrichment

:

enrichr_gene_enrichment_analysis

(libs:

KEGG_2021_Human

,

Reactome_2022

,

GO_Biological_Process_2023

)

Reactome mapping

:

ReactomeAnalysis_pathway_enrichment

,

Reactome_map_uniprot_to_pathways

Network analysis

:

STRING_get_interaction_partners

,

STRING_functional_enrichment

Druggable targets

:

OpenTargets_get_target_tractability_by_ensemblID

Phase 7: Clinical Evidence & Guidelines

Guidelines search

:

PubMed_Guidelines_Search

(fallback:

PubMed_search_articles

)

FDA-approved therapies

:

OpenTargets_get_associated_drugs_by_disease_efoId

,

FDA_get_indications_by_drug_name

Biomarker-drug evidence

:

civic_search_evidence_items

,

civic_search_assertions

Phase 8: Clinical Trial Matching

Biomarker-driven trials

:

clinical_trials_search

with condition + intervention

Precision medicine trials

:

search_clinical_trials

for basket/umbrella trials

Phase 9: Integrated Scoring & Recommendations

Score Components (total 0-100)

Genetic Risk

(0-35): Pathogenicity + gene-disease association + PRS

Clinical Risk

(0-30): Stage/biomarkers/comorbidities

Molecular Features

(0-25): Driver mutations, subtypes, actionable targets

Pharmacogenomic Risk

(0-10): Metabolizer status, HLA alleles

Risk Tiers

Score

Tier

Management

75-100

VERY HIGH

Intensive treatment, subspecialty referral, clinical trial

50-74

HIGH

Aggressive treatment, close monitoring

25-49

INTERMEDIATE

Standard guideline-based care, PGx-guided dosing

0-24

LOW

Surveillance, prevention, risk factor modification

Output

Generate report per

REPORT_TEMPLATE.md

. See

SCORING_REFERENCE.md

for detailed scoring matrices.

Common Use Patterns

See

EXAMPLES.md

for six detailed worked examples:

Cancer + actionable mutation

Breast cancer, BRCA1, ER+/HER2- -> Score ~55-65 (HIGH)

Metabolic + PGx concern

T2D, CYP2C19 PM on clopidogrel -> Score ~55-65 (HIGH)

NSCLC comprehensive

EGFR L858R, TMB 25, PD-L1 80% -> Score ~75-85 (VERY HIGH)

CVD risk

LDL 190, SLCO1B1*5, family hx MI -> Score ~50-60 (HIGH)

Rare disease

Marfan, FBN1 variant -> Score ~55-65 (HIGH)

Neurological risk

APOE e4/e4, family hx Alzheimer's -> Score ~60-72 (HIGH)