OneKGPd: Individual-Level Queries over the 1000 Genomes Project

Scope

This skill queries the 1000 Genomes Project dataset — the extended high-coverage cohort of 3,202 whole-genome-sequenced individuals, on the GRCh38 assembly. All results are drawn from this cohort, and sample names returned by the skill (for example HG00096 or NA21130) identify its participants.

Queries resolve against the cohort's per-individual genotype data. This supports two complementary classes of question: selecting variants carried within a region (across the whole cohort or within a specified set of individuals), and selecting the individuals who carry variants matching given criteria. Variant selection can be filtered by allele frequency, predicted consequence, clinical significance, AlphaMissense classification, and the other annotation axes listed below. Relatedness between two named individuals is also available.

The genotype state in which a variant is carried — heterozygous or homozygous — is a criterion that queries may specify; results are returned as variants or as sample names, not as raw genotypes.

When to Use

Use this skill when you need to:

• Find variants carried in a region or set of regions matching some criteria across the whole cohort (select-variants).
• Find variants carried in a region or set of regions matching some criteria in specific set of individuals (select-variants-in-samples).
• Find which 1000 Genomes individuals carry variants matching some criteria in a region or set of regions (select-samples).
• Count how many individuals carry specific variants (count-samples).
• Restrict any variant query to heterozygous-only or homozygous-only carriage, or query both together (default).
• Identify which individuals are homozygous reference at a single position (select-samples-hom-ref).
• Determine the relatedness between two named 1000 Genomes individuals — both the degree (twin / 1st / 2nd / 3rd / unrelated) and the KING kinship coefficient (kinship).
• Get dataset totals — sample count, sex split, variant count, assembly (dataset-info).
• Variant selection can be specified by KGP allele frequency, gnomAD 4.1 exome and gnomAD 4.1 genome allele frequency, AlphaMissense Score and AlphaMissense Class, ClinVar significance (202502), and VEP annotations (impact, biotype, feature type, variant class, consequences).

Do NOT use this skill for:

• Resolving a gene symbol, rsID, or transcript to coordinates, or fetching reference sequence. Resolve coordinates first (see Coordinate Provenance below), then query this skill with the resolved GRCh38 region.
• Any cohort other than the 1000 Genomes Project — this skill serves only that dataset.

Prerequisites

1. uv: This skill's script is run with uv run, which reads the script's inline dependency metadata and provisions an ephemeral environment. Ensure uv is installed and on PATH (https://docs.astral.sh/uv/).
2. Data use terms: The 1000 Genomes Project data is open; users should be aware of the 1000 Genomes Project / IGSR data-use terms (https://www.internationalgenome.org/data).
3. Access constraints: There is no API key, no .env file, and no rate-limit token to configure.
4. No credentials required

Core Rules

• Use the Wrappers: ALWAYS execute the provided helper scripts rather than constructing your own client calls or network requests. Use scripts/onekgpd_api.py for variant/sample/kinship queries (it handles the connection, streaming, pagination, and JSON serialization), and scripts/onekgpd_meta.py for sample/population metadata (offline, see Sample & population metadata).
• Coordinates MUST be resolved against an authoritative source first — see Coordinate Provenance. This is mandatory, not advisory.
• Count before you select: every variant and sample selection has a paired counting command. Call the count command FIRST to size the result set, then select only if the count is manageable.
• Zygosity defaults to both: selection and counting commands include both heterozygous and homozygous carriage by default. Narrow with --het-only or --hom-only when the question is specifically about one state. (You do not need to pass anything to get both.)
• Output: scripts write full JSON to a file (--output, default under /tmp/) and print a concise summary to stdout. Do not read large JSON files into context — use jq or a small disposable uv run python snippet to extract fields.

Coordinate Provenance (MANDATORY FIRST STEP)

Before any region-based query, resolve the gene or feature to GRCh38 coordinates against an authoritative source (for example Ensembl), and query with those resolved coordinates. The assembly must be explicit, and a gene-range must be resolved to precise positions before use. This is structural, not advisory: there is no source-side guardrail that would catch a misplaced region, so an unverified coordinate produces results for an unintended location with no error.

# Resolve gene symbol -> GRCh38 region with an authoritative source FIRST,
# then pass the verified coordinates to the OneKGPd query below.

[!CAUTION] The dataset is GRCh38. A GRCh37 coordinate, or any region that does not correctly correspond to the intended feature on GRCh38, will return results for an unintended location without raising an error. Verify the assembly and the resolved coordinates before querying.

Command Selection Guide

Match the question to the command. Counting commands are cheap and should precede their selection counterpart.

• Which individuals carry matching variants in a region → count-samples then select-samples
• Which variants are carried in a region, cohort-wide → count-variants then select-variants
• Which variants are carried in a region, within a named set of individuals → count-variants-in-samples then select-variants-in-samples
• Who is homozygous-reference at a single position → count-samples-hom-ref then select-samples-hom-ref
• Relatedness (degree + coefficient) between two named individuals → kinship
• Dataset totals (sample count, sex split, variant total, assembly) → dataset-info

Annotation filters (shared across variant and sample selection/counting)

All variant- and sample-selection commands (count-variants, select-variants, their -in-samples forms, count-samples, select-samples) accept the same annotation filters. Different filter fields are combined with AND; multiple values within one field are combined with OR. Enum values are case-insensitive (e.g. missense_variant or MISSENSE_VARIANT).

These are selection criteria applied on the server. The fields returned on a selected variant are listed under Variant-returning commands; a criterion used for filtering is not necessarily echoed back on the returned variant.

• --af-lt / --af-gt: 1000 Genomes dataset allele frequency bounds
• --gnomad-exomes-af-lt / --gnomad-exomes-af-gt: gnomAD v4.1 exome AF bounds
• --gnomad-genomes-af-lt / --gnomad-genomes-af-gt: gnomAD v4.1 genome AF bounds
• --clin-significance: ClinVar significance terms, CSV (e.g. PATHOGENIC,LIKELY_PATHOGENIC)
• --consequence: Sequence Ontology consequence terms, CSV (e.g. MISSENSE_VARIANT,STOP_GAINED)
• --impact: VEP impact, CSV (HIGH,MODERATE,LOW,MODIFIER)
• --variant-type, --feature-type, --bio-type: SO variant class / VEP feature / VEP biotype, CSV
• --alpha-missense-class: AM_LIKELY_BENIGN,AM_LIKELY_PATHOGENIC,AM_AMBIGUOUS (CSV)
• --alpha-missense-score-lt / `--alpha-missense-score-gt