/genomic-coordinates

name: genomic-coordinates
description: Convert genomic intervals between coordinate conventions, normalise and compare variant representations, and detect assembly or contig-naming mismatches before they corrupt an analysis. Use whenever coordinates cross a format, tool, or assembly boundary - converting between BED, GFF/GTF, VCF, SAM/BAM, WIG, PSL, genePred, Picard interval_list, or region strings; reconciling 0-based half-open with 1-based inclusive; left-aligning or trimming indels; checking whether two variant records describe the same change; mapping genomic to transcript, CDS, or protein positions; auditing a BED/GTF/VCF for convention violations; or diagnosing GRCh37 vs hg19 vs GRCh38 vs T2T, chr-prefix, and liftover problems. Triggers include "off by one", "0-based", "1-based", "half-open", "coordinate system", "left-align", "normalize variant", "bcftools norm", "chr prefix", "wrong genome build", "liftover", "REF mismatch", and "HGVS".
license: MIT
compatibility: Requires Python 3.11+. Scripts use only the standard library - no third-party packages and no network access. Variant normalisation needs a reference FASTA, and uses its .fai index when one is present.
allowed-tools: Read Write Edit Bash
metadata:
  version: "1.1"
  skill-author: K-Dense Inc.

Genomic Coordinates

When to use

Any time a coordinate crosses a boundary: between two file formats, between two tools, between two assemblies, or between the genome and a transcript.

The rule

**A coordinate is three facts, not one: the number, the convention it is written in, and the assembly it was measured against.** Carry all three or the number is not interpretable.

Coordinate errors are the quietest class of bug in genomics. An off-by-one BED file parses, sorts, and intersects without complaint. A GRCh37 VCF joined against a GRCh38 annotation returns rows. A right-shifted indel simply fails to match its entry in ClinVar, and the result is a variant reported as novel. Nothing raises an error; the answer is just wrong, and it is wrong in a direction that looks plausible.

So: convert with the table, not from memory, and verify against the reference whenever a reference is available.

The two conversions

1-based inclusive  ->  0-based half-open :  start - 1,  end
0-based half-open  ->  1-based inclusive :  start + 1,  end

The end coordinate never moves. If a conversion changed both numbers, it is wrong.

Which format is which

| 0-based, half-open | 1-based, inclusive | | --- | --- | | BED, bedGraph, bigWig, narrowPeak | GFF3, GTF, VCF | | BAM/CRAM (binary POS) | SAM (text POS) | | PSL, genePred, refFlat | WIG, Picard interval_list | | MAF (UCSC multiple alignment) | MAF (TCGA mutation annotation) | | PyRanges, pybedtools | GRanges/IRanges, samtools & UCSC & Ensembl region strings |

Both "MAF" formats exist, they mean different things, and they disagree. UCSC serves 0-based files through a 1-based browser box. `references/format-conventions.md` has the full table with per-format detail.

cd skills/genomic-coordinates/scripts

python3 convert_coords.py --list                          # the table
python3 convert_coords.py --from bed --to gff chr1 999 1000
python3 convert_coords.py --from ucsc --to bed "chr7:5,530,601-5,530,625"
python3 convert_coords.py --from granges --to pyranges --input regions.tsv

contig  input                 output           length  status  detail
chr7    chr7:5530601-5530625  5530600-5530625  25      ok

Zero-length BED features (`chromStart == chromEnd`, a legal insertion point) are reported as `unrepresentable` rather than converted to `end = start - 1`. Exit code is 1 when any interval is degenerate or invalid.

Variants are not intervals

A VCF `POS` for an indel is the **anchor base** — the base *before* the event, itself unchanged. And the same change can be written many ways: `chr1:7:CAC:C`, `chr1:3:CAC:C` and `chr1:2:GCA:G` are one deletion. Joining, deduplicating, or looking up variants before normalising loses real matches silently, and it loses them preferentially in repeats, where indels concentrate.

Normalise — trim to parsimony, then left-align against the reference — before any comparison:

python3 normalize_variant.py --fasta ref.fa chr1 7 CAC C
python3 normalize_variant.py --fasta ref.fa --split --input cohort.vcf
python3 normalize_variant.py --fasta ref.fa --compare chr1:7:CAC:C chr1:2:GCA:G

input         normalized    type      pos_shift  ref_check  changed
chr1:7:CAC:C  chr1:2:GCA:G  deletion  5          ok         yes

Every record's `REF` is checked against the FASTA first. A `MISMATCH` means the variants and the reference are different assemblies — stop and run `check_contigs.py` rather than adjusting coordinates. Multi-allelic records must be split with `--split` **before** normalising, never after.

HGVS shifts indels the opposite way, 3'-most along the transcript. For a minus-strand gene that is the opposite genomic direction from VCF's left-alignment. Details and the full procedure: `references/variant-representation.md`.

Check the assembly before trusting a join

python3 check_contigs.py --identify unknown.fa.fai
python3 check_contigs.py variants.vcf annotation.gtf --genome GRCh38.fa.fai

file          kind    contigs  naming        assembly  detail
ref.fa.fai    sizes   25       plain         GRCh37    24/24 primary chromosome lengths match;
                                                       chrM is 16569 bp, i.e. GRCh37/38 (rCRS MT)

The script reads `.fai`, `.chrom.sizes`, VCF headers, SAM headers, FASTA, BED, and GTF/GFF, identifies the assembly from primary-chromosome lengths, and reports every reason a join between two files would go wrong: naming mismatch, length conflict, coordinates past a contig end, contigs present in one file only. Exit code 1 on any incompatibility.

**GRCh37 and hg19 differ only in the mitochondrion** — 16,569 bp (rCRS) versus 16,571 bp. N