V2 CN: CYTO-042 results (precision up, mosaic calls halved); pi_run reports process memory without page cache
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@@ -62,7 +62,8 @@ duplications labelled mosaic (43 % in truth).
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| base (per-probe reference het BAF spread in the emissions) | 22 / 100 % | 3 / 67 % | 29 / 11 % | 24 / 38 % | 80 % |
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| `--mosaic-prior 0.0005` | 25 / 96 % | 4 / 75 % | 27 / 12 % | 22 / 36 % | 80 % |
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| `--mosaic-prior 0.0005 --switch-distance 1e8` | 24 / 96 % | 4 / 75 % | 25 / 14 % | 23 / 35 % | 80 % |
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| CYTO-041 (noise-normalised BAF split, complete-loss promotion) | 27 / 93 % | 4 / 75 % | **19** / 5 % | **19** / 42 % | 80 % |
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| CYTO-041 (noise-normalised BAF split, complete-loss promotion) | 27 / 93 % | 4 / 75 % | 19 / 5 % | 19 / 42 % | 80 % |
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| + CYTO-042 (per-probe LRR noise from the reference; **default**) | 20 / **100 %** | 4 / **100 %** | **11** / 9 % | **13** / **62 %** | 80 % |
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* The mosaic prior and switch distance barely matter. CYTO-041 moves heterozygote-free "mosaic" losses (compressed
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constitutional deletions) to DEL (`HIGHFRACTION`) and sends noise-driven mosaic calls to `LowFraction`
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@@ -71,6 +72,11 @@ duplications labelled mosaic (43 % in truth).
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* Remaining mosaic-loss false positives are long, low-amplitude LRR dips (−0.05 … −0.1) with a heterozygous BAF
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spread only 1.0–1.3 × the probe's reference spread, or short events with < 20 heterozygous probes (MF from LRR).
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Without phasing a < 20 % mosaic loss cannot be separated from regional BAF noise (K-027).
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* CYTO-042 (per-probe emission SD = sample SD × the probe's reference LRR spread / median spread, clipped to
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[0.5, 3]) halves the mosaic calls and makes constitutional calls fully precise, at the cost of 5 rare deletions
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(rare DEL 24/64 → 19/64; rare DUP 10/68 → 12/68). Synthetic set with the rebuilt model (`data/v2cn/syn4`): calls
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564 → 402, detection 126 → 124/216, the CYTO-022 gate (15 % / 5 Mb: 4/4 loss, gain, CN-LOH) still passes.
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Disable with `--no-probe-lrr-sd`.
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* **Sensitivity is limited by common CNVs.** Detected truth DEL by carrier frequency among the 120 individuals:
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< 5 %: 24/64 (38 %), 5–20 %: 1/20, 20–50 %: 1/80, > 50 %: 0/156 (DUP 10/66, 0/2, 1/24, 0/40). The batch
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reference is the per-probe median LRR, so an event carried by most reference samples is normalised away (and the
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@@ -79,8 +85,7 @@ duplications labelled mosaic (43 % in truth).
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## Next steps
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1. Report sensitivity for rare events (carrier frequency < 5 %) as the primary metric in `cn_validate_truth.py`.
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2. Mosaic losses: phasing-based BAF (MoChA-style) is the principled fix for low fractions; until then consider a
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minimum heterozygous-probe count for mosaic PASS calls.
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3. Sensitivity for 25–500 kb events: per-probe LRR SD from the reference.
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4. A final full-cohort run (cloud, ~$0.10, needs approval) once the above settle.
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1. Mosaic losses below ~20 %: phasing-based BAF (MoChA-style, MIT) is the principled fix.
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2. Rare-event sensitivity (currently DEL 30 %, DUP 18 % for events ≥ 25 kb with ≥ 10 probes): exclude reference
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samples carrying the event when computing the per-probe median (iterative reference), size-aware transitions.
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3. A final full-cohort run (cloud, ~$0.10, needs approval).
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