CN: MF split normalised by per-probe reference BAF noise; genotype-based complete loss (CYTO-041)
The mosaic BAF split is now estimated over heterozygous calls against each probe's expected noise (the reference heterozygous spread scaled to the sample), inverting the median of |N(+-d, sigma)|. A mosaic loss lacking the heterozygous calls its PFB predicts gets MF 1 and is promoted (CYTO-020).
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@@ -2437,13 +2437,15 @@ about **algorithms or numerics**, the plan wins. Each such conflict found during
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- **CYTO-041** `§10.3 · v2` **MF refinements [OURS].** Two refinements of CYTO-018, from real-data validation
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(docs/validation/V2_cn.md, K-027):
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- *noise-corrected split:* the median |BAF − 0.5| of unsplit heterozygotes is 0.6745·σ_b (σ_b = the sample's
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heterozygous BAF SD), so `d = √max(0, d_obs² − (0.6745·σ_b)²)`. Without this, noise alone gave MF ≈ 0.2 in
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diploid regions and waves were called as mosaic losses.
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- *complete loss:* a mosaic loss with ≥ 20 finite-BAF probes, ≥ 5 expected heterozygotes (Σ 2p(1−p) over PFB p),
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and fewer than 0.25 × expected probes with 0.1 < BAF < 0.9 has MF = 1. With the default
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`--max-mosaic-fraction 1.0` it is therefore promoted (CYTO-020) to a constitutional DEL with `HIGHFRACTION`.
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This catches constitutional deletions whose LRR is compressed towards the mosaic states.
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- *noise-corrected split:* per-probe expected noise σ_i = the reference's heterozygous BAF spread of the probe ×
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the sample's scale (median |BAF − 0.5| / spread over autosomal heterozygous calls, ÷ 0.6745; the sample's
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heterozygous BAF SD without a reference spread). Over the event's heterozygous calls, m = median(|BAF − 0.5| /
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σ_i); the split in σ units δ solves Φ(m − δ) − Φ(−m − δ) = ½ (δ = 0 when m ≤ 0.6745) and d = median(σ_i)·δ.
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Without this, noise alone gave MF ≈ 0.1–0.3 and genomic waves were called as mosaic losses.
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- *complete loss:* a mosaic loss whose called genotypes hold fewer than a quarter of the heterozygotes the PFB
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predicts (Σ 2p(1−p) ≥ 3) has MF = 1. With the default `--max-mosaic-fraction 1.0` it is therefore promoted
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(CYTO-020) to a constitutional DEL with `HIGHFRACTION`. This catches constitutional deletions whose LRR is
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compressed towards the mosaic states.
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---
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