exon-research/genomi/pharmacogenomics

Pharmacogenomics

Use this skill when the user asks about medication response, PGx guidelines, drug-gene or variant-drug evidence, PGxDB, ATC codes, DrugBank IDs, PharmCAT, or pharmacogene sample evidence.

Contract

• Drug-response claims use public PGx source evidence.
• Personal drug-response statements cite separate local genotype or PGx caller

support.

• External PGx lookups receive selected public targets only.
• Source-backed PGx findings can be stored as shared reviewed research.
• User-specific sample interpretations can be stored as private reviewed

research.

Convention: See skills/conventions/evidence-quality.md.

Convention: See skills/_output-rules.md.

Primary Flow

1. Use pharmacogenomics.review_medication for ordinary medication questions.

It combines ClinPGx, FDA PGx tables, PGxDB, stored reviewed research, and optional selected sample evidence in one bounded review.

1. Inspect evidence_envelope, medication_review_matrix,

evidence_matrix, target_inventory, answer_support, and unanswered_answer_components before answering. Treat each medication_review_matrix.rows[] entry as the review unit.

1. If the answer needs source review beyond returned public records, use

research.list_sources, review the selected public target, then store the finding with research.record.

1. If the answer needs personal sample evidence, use the Active Genome Index

only when selected or supplied in this chat. Confirm relevant alleles with variant.resolve or active_genome_index.classify_genotype_support.

Tool Choices

• pharmacogenomics.review_medication: bounded medication evidence review;

public-only by default, with Active Genome Index evidence when selected.

• pharmacogenomics.fetch_clinpgx, pharmacogenomics.fetch_fda_labels, and

pharmacogenomics.fetch_pgxdb: focused public PGx source retrieval when the medication review needs a source-specific follow-up.

• pharmacogenomics.describe_gene_requirements: gene-specific sample evidence

requirements for named allele matching, outside calls, HLA, MT-RNR1, G6PD, and SV/CNV-sensitive genes.

• pharmacogenomics.check_pharmcat: check local PharmCAT availability.
• pharmacogenomics.preflight_pharmcat: inspect whether the selected Active

Genome Index can provide a suitable PharmCAT input before running it.

• pharmacogenomics.prepare_outside_call_tsv and

pharmacogenomics.validate_outside_call_tsv: prepare or validate specialized outside-call evidence for PharmCAT.

• pharmacogenomics.run_pharmcat: run broad PharmCAT calling from the selected

Active Genome Index and return provenance plus sample_pgx_matrix rows projected from report, phenotype, calls-only, and matcher artifacts.

• pharmacogenomics.import_pharmcat_artifacts: import existing PharmCAT JSON,

TSV, matcher, phenotype, missing-position, or output-directory artifacts and return sample_pgx_matrix.

PGx capability metadata is exposed through genomi.list_resources; there is no separate PGx capability-listing tool.

Answering

• Mention Active Genome Index evidence only when it changes the medication

interpretation, limitation, blocker, or next action.

• Keep PGx language informational and recommend clinical confirmation for

medication decisions.

• Do not infer medication actionability from a genotype alone; connect sample

evidence to public drug-response evidence.

• Treat user-provided diplotypes, phenotypes, activity scores, and outside

calls as supplied sample evidence that may need independent confirmation.

Cross-Capability Synthesis

A scope-limited result from this capability is not a final user-facing answer when other Genomi capabilities can contribute orthogonal evidence to the same question. Returning "cannot answer" while applicable capabilities remain unexamined is a host-agent failure mode.

Tools

pharmacogenomics.check_pharmcat

Check local PharmCAT availability and version provenance for broad PGx calling from an AGI-derived PharmCAT input.

Use when: The agent needs to know whether broad PharmCAT PGx calling is available before running pharmacogenomics.run_pharmcat.

Why necessary: External PGx calls need availability and version provenance before they are trusted.

Result semantics: Reports local PharmCAT executable/jar availability and version probe output for auditability before broad PGx calling.

pharmacogenomics.describe_gene_requirements

Return pharmacogene-specific sample evidence requirements for PharmCAT named allele matching, outside calls, CYP2D6 SV/CNV handling, HLA typing, MT-RNR1, and G6PD chrX representation.

Use when: The selected medication or source evidence names a pharmacogene and the agent needs to choose sample evidence, PharmCAT, outside-call, or targeted lookup handling.

Why necessary: Complex pharmacogenes require special evidence handling that a simple rsID lookup cannot provide.

Result semantics: Returns packaged source-backed pharmacogene sample-evidence requirements, candidate tools, and source references for the selected gene.

pharmacogenomics.fetch_clinpgx

Fetch traceable ClinPGx pharmacogenomic guideline, clinical annotation, and FDA label evidence for a selected drug, gene, or rsID; compact normalized records are returned by default.

Use when: The question involves medication response, adverse effects, CPIC/DPWG guidance, FDA drug-label PGx context, PharmGKB/ClinPGx annotations, or drug plus gene/rsID interpretation.

Why necessary: Guideline, clinical annotation, and label rows are separate public PGx evidence from sample genotype calls.

Result semantics: Fetches public guideline, annotation, and label rows; raw API records are opt-in with include_raw_records; personal interpretation requires separate local genotype or diplotype evidence.

pharmacogenomics.fetch_fda_labels

Fetch targeted FDA pharmacogenomic biomarker-labeling and pharmacogenetic-association table rows from official FDA pages.

Use when: The question needs FDA biomarker-labeling table context or FDA pharmacogenetic association table context for a selected drug or gene.

Why necessary: FDA biomarker and pharmacogenetic-association tables are official label evidence with their own boundaries.

Result semantics: Fetches official FDA table rows; keep biomarker-labeling rows separate from pharmacogenetic-association rows and combine with separate sample evidence for personal interpretation.

pharmacogenomics.fetch_pgxdb

Fetch targeted PGxDB pharmacogenomic evidence for a selected drug, ATC code, DrugBank ID, rsID, variant marker, or gene.

Use when: The question involves medication response, adverse effects, pharmacogenomics, PharmGKB-style evidence, a drug plus rsID, or a drug plus gene.

Why necessary: PGxDB association records provide targeted drug-variant evidence distinct from guideline recommendations.

Result semantics: Fetches public PGxDB rows; sample interpretation requires separate local genotype evidence.

pharmacogenomics.import_pharmcat_artifacts

Import existing PharmCAT report JSON, calls-only TSV, matcher JSON, phenotype JSON, missing-position VCF, or output directory without executing PharmCAT.

Use when: The agent has existing PharmCAT artifacts and needs sample-side PGx evidence without running local PharmCAT.

Why necessary: Existing PharmCAT outputs should be reused rather than rerun when sample-side PGx evidence already exists.

Result semantics: Parses existing PharmCAT artifacts into sample_pgx_matrix, evidence summaries, and record_research_payloads used by pharmacogenomics.run_pharmcat, including interpretation readiness and missing-position review facts.

pharmacogenomics.preflight_pharmcat

Inspect selected Active Genome Index structure for broad PharmCAT PGx calling without running PharmCAT or writing artifacts.

Use when: The agent needs read-only Active Genome Index structure, sample-column, genotype-field, or header evidence before broad PharmCAT PGx calling.

Why necessary: Broad PharmCAT runs need input suitability checks before execution or artifact interpretation.

Result semantics: Returns local AGI-derived preflight facts without exposing the raw AGI path; PharmCAT coverage sufficiency is judged from execution artifacts, especially missing PGx position review.

pharmacogenomics.prepare_outside_call_tsv

Prepare a PharmCAT outside-call TSV from supported specialized caller output such as OptiType HLA calls, StellarPGx CYP2D6 summaries, or generic gene/diplotype tables.

Use when: The agent has specialized caller output for HLA-A, HLA-B, CYP2D6, MT-RNR1, or another pharmacogene and needs a PharmCAT outside-call TSV.

Why necessary: Specialized callers for HLA, CYP2D6, and related genes need conversion before PharmCAT can consume them.

Result semantics: Writes a canonical outside-call TSV under Genomi output storage or the requested output_file, validates it, and returns output.path for pharmacogenomics.run_pharmcat with parsed rows, invalid rows, warnings, caller format, and sample identity facts.

pharmacogenomics.review_medication

Review medication pharmacogenomic evidence as medication-first rows combining ClinPGx guideline/label context, FDA PGx table rows, PGxDB association evidence, Active Genome Index rsID lookup when selected, implemented marker-definition evidence when selected, evidence components, and target inventory.

Use when: Combines public PGx evidence with selected active-genome-index or marker evidence for one medication.

Why necessary: Medication-response questions need drug-specific PGx sources plus optional personal genotype evidence in one bounded review.

Not for: diagnosing disease risk; it is medication-response evidence.

Example prompts: Does my DNA say anything about clopidogrel?

Result semantics: Returns medication_review_matrix where each row carries drug, gene, variant/diplotype/phenotype, recommendation/source text, evidence IDs, sample relevance, row readiness, and clinical boundary. Public-only by default unless active-genome-index context is selected.

pharmacogenomics.run_pharmcat

Run a local PharmCAT installation from an approved Active Genome Index for broad PGx diplotype, phenotype, recommendation artifacts, and sample_pgx_matrix rows.

Use when: Runs local PharmCAT from the selected Active Genome Index to generate broad PGx diplotype, phenotype, and recommendation artifacts.

Why necessary: Broad PGx diplotype and recommendation artifacts require a specialized external caller.

Result semantics: Runs local PharmCAT as sample-side PGx evidence generation; returns input preflight, runtime provenance, outside-call validation, sample_pgx_matrix, artifacts, warnings, interpretation readiness, and record_research_payloads for synthesis.

pharmacogenomics.validate_outside_call_tsv

Validate PharmCAT outside-call TSV structure and summarize selected diplotype, phenotype, or activity-score evidence.

Use when: The PGx sample evidence path already has a PharmCAT outside-call TSV for CYP2D6, HLA-A, HLA-B, MT-RNR1, or another specialized caller result before PharmCAT execution.

Why necessary: Outside calls can override complex gene evidence, so their structure must be validated before use.

Result semantics: Validates outside-call TSV shape, hides the local path, returns parsed rows, invalid rows, warnings, and explains that outside calls override PharmCAT VCF-derived calls for the same gene.