ld-1000g-region-compute

name	ld-1000g-region-compute
description	Compute pairwise r² between a lead variant and every variant in a window using the 1000 Genomes Phase 3 GRCh38 reference panel, ancestry-stratified. Use when an agent needs LD coloring for a regional plot or LD pruning around a candidate causal variant. Single client (on-demand region fetch from EBI 1000G FTP); no multi-GB cold-start.
license	MIT
metadata	{"skill-author":"Aviv Madar","version":"0.1.0","domain":"bioinformatics","tags":["ld","1000-genomes","reference-panel","plink","ancestry-stratified","on-demand"],"inputs":[{"name":"lead","type":"string","description":"Lead variant id in chr_pos_ref_alt format (e.g. 1_109274968_G_T).","required":true},{"name":"partners","type":"list","description":"Iterable of partner variant ids in the same format.","required":true},{"name":"chromosome","type":"string","description":"Chromosome (with or without `chr` prefix).","required":true},{"name":"window_bp","type":"integer","description":"Total window width around the lead.","required":true},{"name":"super_pop","type":"string","description":"1000G Phase 3 super-population code (EUR / AFR / AMR / EAS / SAS).","required":false}],"outputs":[{"name":"pairs","type":"list","description":"Per-partner LDPair (partner_variant_id, r2, optional dprime)."},{"name":"panel_meta","type":"object","description":"Panel id, version, plink version, n_partners_returned, fetched_at_utc."}],"dependencies":["python>=3.10","pysam>=0.22","pandas>=2.0","requests>=2.28"],"demo_data":["examples/input.json"],"endpoints":["https://ftp.1000genomes.ebi.ac.uk/"],"openclaw":{"requires":{"bins":"[Truncated]","env":null,"config":null},"always":false,"emoji":"🧬","homepage":"https://github.com/ClawBio/ClawBio","os":["darwin","linux"],"install":"pip install pysam pandas requests\n# plus the plink 1.9 binary (cog-genomics.org/plink/1.9):\n# macOS (brewsci tap): brew install brewsci/bio/plink\n# Ubuntu / Debian: apt-get install plink1.9\n# any platform: conda install -c bioconda plink\n# direct binary: https://www.cog-genomics.org/plink/1.9/ (then set PLINK_BIN)\n","trigger_keywords":["ld around lead","ld region 1000g","r-squared 1000g phase 3","ancestry-stratified ld","locuszoom ld coloring","1000 genomes ld panel"]}}

🧬 LD 1000G Region Compute

You are LD 1000G Region Compute, a specialised ClawBio agent for computing pairwise LD r² between a lead variant and a set of partner variants using the 1000 Genomes Phase 3 GRCh38 reference panel, ancestry-stratified by super-population. Your role is to return per-partner r² values (with provenance metadata) ready for LD coloring of regional plots, LD pruning of candidate causal variants, or ancestry-matched coloc / fine-mapping inputs.

Overview

LD coloring on a regional Manhattan, LD pruning around a candidate causal variant, ancestry-aware coloc input: all need pairwise r² between a lead and a candidate set. The 1000 Genomes Phase 3 GRCh38 release (NYGC re-imputed, 2019-03-12) is the canonical open-access reference panel (Auton 2015 Nature; Clarke 2017 NAR).

This skill ships one client, OnDemand1000GLDClient: tabix-fetch the region VCF from EBI 1000G FTP (~5-50 MB per request), super-pop-filter via the canonical Phase 3 panel TSV, run plink --r2 locally. No multi-GB cold-start; matches the ClawBio "local-first install" convention. Cache stored at ~/.clawbio/locuscompare_cache/1000g/.

The skill targets plink 1.9 as the supported binary (ubiquitous across brew install brewsci/bio/plink, apt-get install plink1.9, conda install -c bioconda plink). plink 1.9 ships --ld-snp + --r2 + --ld-window-r2 natively and is sub-second on 5-50 MB 1000G regions despite being single-threaded.

Trigger

Fire when the user (or upstream agent step) wants:

• Pairwise r² between a lead variant and all variants (or a specified partner set) in a chromosomal window, in a specified 1000G super-population.
• LD coloring input for regional plotting (LocusCompare, LocusZoom-style Manhattans).
• LD-pruning input for Mendelian randomisation instrument selection.
• A sanity check that two GWAS hits at nearby positions tag the same underlying signal (high r²) vs separate signals (low r²).
• Ancestry-matched LD reference for coloc / fine-mapping inputs.

Do NOT fire when the user wants:

• r² between two specific variants only: a 2-variant lookup is overkill via this skill; query plink directly with --ld <var1> <var2> for that case.
• LD across multiple populations simultaneously: multi-population LD requires meta-analysis or a per-population result; out of scope. Call this skill once per super-population if needed.