Fix off-by-one in predict_variant_effect ref-allele check

[lucapinello]

Problem

The ref-allele sanity check at chorus/core/base.py:322 was reading the base one position to the right of what the user asked for. So

predict_variant_effect(
    genomic_region="chr1:109274000-109275000",
    variant_position="chr1:109274968",
    alleles=["G", "T"],       # rs12740374, as in dbSNP/UCSC
    ...
)

triggered

WARNING  Provided reference allele 'G' does not match the genome at this
         position ('T'). Chorus will use the provided allele.

even though G at chr1:109274968 is exactly what dbSNP/UCSC/IGV/extract_sequence('chr1:109274968-109274968') all say. The substitution at line 335 then placed the ref/alt base at pos+1, so every shipped walkthrough was computing predictions at the wrong coordinate. The regulatory signal happens to be coherent across ±1 bp on rs12740374, rs1421085, rs1427407 etc., so effect directions still reproduced — which is why this has been shipping.

Root cause

• genomic_region / variant_position strings follow dbSNP/UCSC/IGV and chorus.utils.extract_sequence — 1-based inclusive.
• GenomeRef uses 0-based half-open (documented at interval.py:26).
• predict_variant_effect handed the 1-based values straight to GenomeRef and to ref2query, conflating the two conventions.

Fix

Convert region_start and var_pos to 0-based at the point we build the Interval. That's it — just two -1s with an explanatory comment.

Verification

Tested against 7 famous SNPs — for every one, the internal ref-check now agrees with extract_sequence and dbSNP:

rsID	Gene	hg38	dbSNP ref	internal (before)	internal (after)
rs12740374	SORT1	chr1:109274968	G	T	G ✓
rs1421085	FTO	chr16:53767042	T	A	T ✓
rs1427407	BCL11A	chr2:60718347	G	C	G ✓
rs4988235	LCT	chr2:135851076	G (+ strand)	C	G ✓
rs334	HBB	chr11:5227002	T (+ strand)	C	T ✓
rs6025	F5 Leiden	chr1:169519049	T (+ strand)	C	T ✓
rs7412	APOE	chr19:44908822	C	G	C ✓

Also works for the MCP _auto_region case (a 2 bp region exactly spanning the variant) — the old code silently read pos+1; the fix correctly lands on pos.

New regression test

tests/test_prediction_methods.py::test_variant_position_is_1_based builds a synthetic genome with a single G anchor at 1-based position 100,000 and asserts:

• no warning when the user passes ref='G'
• warning does fire when the user passes ref='T' (proves the check still catches real mismatches — we haven't just silenced it)

Scope

Only predict_variant_effect is touched. predict_region_replacement and predict_region_insertion_at also treat their string coordinates as 0-based half-open internally; changing those would silently shift existing sequence-engineering results by 1 bp, so that's deferred to a separate PR with example-output regeneration.

Downstream consequence

Variant effect predictions will now substitute the ref/alt base at the correct 1-based position. Effect sizes in the shipped walkthroughs may drift by a small amount relative to the currently committed example_output.* files (±1 bp shift in where the substitution lands). Recommend regenerating those in a follow-up once this merges — the effect direction and magnitudes should stay within CPU non-determinism for AlphaGenome, and will likely shift more noticeably for ChromBPNet (1 bp native resolution) where a 1-bp shift lands on a different bin.

Test plan

• pytest tests/ --ignore=tests/test_smoke_predict.py -q → 334 passed / 1 skipped (up from 333 — the new test)
• Manual check against 7 famous SNPs — all consistent
• Regression test validates both the fixed path and the still-working mismatch path

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