Make the sex-linked contig configurable in CNV frequency analysis

[khushthecoder]

Summary

Fix #1313.

gene_cnv_frequencies() and gene_cnv_frequencies_advanced() hardcoded region.contig == "X" when deciding the expected copy number per sample. That is correct for every currently supported assembly, but bakes in a gambiae-complex assumption: any future species whose sex-linked contig uses a different name would silently fall through to the diploid branch and report incorrect amplification / deletion frequencies for hemizygous males.

Because CNV frequencies directly inform insecticide resistance surveillance, silent misclassification of the sex-linked contig is a correctness issue, not a cosmetic one.

Change

Configurable sex_contig

• Added a sex_contig constructor parameter to AnophelesGenomeSequenceData, defaulting to "X", and exposed a matching public sex_contig property. This mirrors the existing pattern used for virtual_contigs.
• Threaded sex_contig through AnophelesDataResource.__init__ so species subclasses can override it at construction time without touching the frequency analysis code.

Single source of truth for expected copy number

• Replaced both hardcoded "X" sites in cnv_frq.py with a shared _expected_copy_number() helper, which consults self._sex_contig and encapsulates all ploidy logic in one place.

Explicit handling of missing sex_call

Previously, requesting the sex-linked contig with a sample frame that happened to lack sex_call (e.g. an As1-style resource) would raise a bare KeyError from deep inside pandas. Now it emits a UserWarning and falls back to diploid for all samples, which is the safest interpretation when sex is unknown. Users get a clear message rather than an opaque crash, and the fallback behaviour is documented in the helper's docstring.

Backwards compatibility

• Default sex_contig="X" keeps behaviour identical for Ag3, Af1, As1, and every other existing resource.
• No public API removed or renamed.
• The new sex_contig property is additive.
• The new UserWarning only fires on a code path that previously raised KeyError, so nothing that used to succeed now warns.

Test plan

• pre-commit run --files … — passed (ruff, ruff-format, trailing-whitespace, end-of-file)
• poetry run mypy … — passed (no issues)
• poetry run pytest tests/anoph/test_cnv_frq.py — 68 passed
• poetry run pytest tests/anoph/test_genome_sequence.py tests/anoph/test_base.py — 62 passed
• poetry run pytest tests/anoph/test_dipclust.py — 64 passed (exercises AnophelesCnvFrequencyAnalysis via the diplotype clustering path)
• CI matrix on PR (linting, coverage, tests across Python 3.10 / 3.11 / 3.12 × numpy ==2.0.2 and >=2.0.2,<2.1)

Files

File	Change
malariagen_data/anoph/genome_sequence.py	Add sex_contig init param + public property.
malariagen_data/anopheles.py	Thread sex_contig through AnophelesDataResource.
malariagen_data/anoph/cnv_frq.py	Introduce _expected_copy_number() helper; remove hardcoded "X"; add sex_call fallback warning.

[khushthecoder]

Hi @jonbrenas — thanks again for merging #1304.

When you have a spare moment, I'd appreciate a look at this pr as well. It closes #1313 (the hardcoded "X" sex-contig in cnv_frq.py) by threading a configurable sex_contig through AnophelesGenomeSequenceData with a default of "X", so behaviour is unchanged for Ag3/Af1/As1 but non-gambiae assemblies can opt in. Local checks pass and CI is green. No rush — whenever it fits your queue.

[codecov]

Codecov Report

❌ Patch coverage is 78.57143% with 3 lines in your changes missing coverage. Please review.
✅ Project coverage is 89.05%. Comparing base (06563cf) to head (087182e).
⚠️ Report is 24 commits behind head on master.

Files with missing lines	Patch %	Lines
malariagen_data/anoph/cnv_frq.py	80.00%	2 Missing ⚠️
malariagen_data/anoph/genome_sequence.py	75.00%	1 Missing ⚠️

❌ Your patch check has failed because the patch coverage (78.57%) is below the target coverage (80.00%). You can increase the patch coverage or adjust the target coverage.

Additional details and impacted files

@@            Coverage Diff             @@
##           master    #1314      +/-   ##
==========================================
+ Coverage   88.88%   89.05%   +0.17%     
==========================================
  Files          56       57       +1     
  Lines        6439     6508      +69     
==========================================
+ Hits         5723     5796      +73     
+ Misses        716      712       -4     

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[khushthecoder]

Hi @jonbrenas — gentle follow-up on this one whenever you get a chance.

Quick status:

All CI checks are green (linting, coverage job, and tests across Python 3.10 / 3.11 / 3.12 × both numpy pins).
The diff is small and fully backwards-compatible: sex_contig defaults to "X", so Ag3, Af1, As1, and every existing resource keep identical behaviour. Non-gambiae assemblies can simply override it at construction time.
Codecov flagged patch coverage at 78.57% (target 80%). The uncovered lines are the defensive branches inside _expected_copy_number() — happy to add a small unit test targeting them directly if you'd prefer the patch to clear the threshold before merge, just let me know.
No rush at all — thanks for your time.

[jonbrenas]

I don't think there is a species for which the sex chromosomes are known and not named 'X' and 'Y'.

[khushthecoder]

I don't think there is a species for which the sex chromosomes are known and not named 'X' and 'Y'.

Thanks for the quick reply, @jonbrenas — that's a fair point, and I agree: for every assembly
this library currently targets (and realistically any that would ever ship here), the sex
chromosome is "X". So the "future non-X contig" framing in the original PR description is
weaker than I made it out to be.

That said, there are two pieces in the diff that stand on their own regardless of the
configurability:

1. sex_call safety guard — the current code accesses df_samples["sex_call"]
   unconditionally inside the X branch (cnv_frq.py:294 and :561). If a sample set ever lacks
   that column — plausible for a newer species where sex calling hasn't been run yet — it surfaces
   as a bare KeyError from inside pandas. The PR turns that into an explicit UserWarning with a
   diploid (CN=2) fallback, which I think is the safer default when sex is unknown.

2. Single source of truth — the literal region.contig == "X" is duplicated across two
   methods (cnv_frq.py:293 and :560). Extracting a small _expected_copy_number() helper
   removes the duplication and makes the ploidy logic explicit in one place, without adding real
   complexity.

Since sex_contig defaults to "X", there's zero behaviour change for Ag3, Af1, or As1 —
existing notebooks and downstream code keep working identically.

Happy to go in whichever direction you prefer:

• Keep only (1) and (2) — drop the sex_contig constructor parameter and public property
  entirely, leaving just the helper refactor and the sex_call guard. Much smaller diff.
• Keep as-is if the configurability is worth having as defensive scaffolding.
• Close the PR if you don't think the motivation justifies the surface-area change — totally
  your call, no hard feelings.

Let me know which you'd like and I'll push the change (or close it) today.