kemal
a4c9c2d7d8
- qc/controls: canonical control names (QC-002), bkg/offset (QC-003), 13 genotyping metrics (QC-004/005), missing/zero-divisor handling (QC-007/008); controls_raw.tsv / controls_qc.tsv (QC-009/011) incl. compat CSVs - qc/thresholds + profiles: YAML schema, validation codes, precedence, shipped profiles, auto (QC-020..025) - qc/status: functional PASS/FAIL/NA, control CLEAR/FLAGGED, flags (QC-030..033) - qc/contamination: BAF regression; bit-compatible with gtc2vcf BAFregress (36/36, K-017), exact mode too - qc/relatedness: KING-robust, duplicates, Mendelian errors, pedigree from sheet (IN-018) - qc/locus_summary: OUT-072, bit-identical to BeadArrayFiles except ChiTest (K-018) - qc/suggest: suggest-thresholds (QC-026) - pipeline/qc: disk-backed cohort store; CLI qc controls|samples|contamination|relatedness|loci|suggest-thresholds - genotype: control tables (OUT-070), het_rate, QC columns, cohort QC - tests: unit + oracle (BAFregress plugin, BeadArrayFiles locus summary)
26 lines
6.1 KiB
Markdown
26 lines
6.1 KiB
Markdown
# Known unknowns and findings log
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Plan §20 lists the open questions; this file records what the implementation has learned. Newest first.
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| ID | Date | Topic | Finding | Status |
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|---|---|---|---|---|
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| K-019 | 2026-09-28 | GSA demo relatedness | The 36-sample GSA v4 PGx demo set contains duplicate/replicate pairs (KING φ ≈ 0.50, concordance ≥ 0.9999) and first-degree relatives (φ ≈ 0.25); without a pedigree they are flagged `duplicate_of:`/`unexpected_relatedness` as designed. Useful as a small relatedness fixture. | documented |
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| K-018 | 2026-09-28 | Locus-summary ChiTest_P100 | Against BeadArrayFiles `locus_summary.py` all columns are bit-identical on 36 GSA samples (683 054 loci) except ChiTest_P100, which differs by ≤ 3.6e-15 relative in ~15 % of loci: scipy 1.18's `ndtr` matches neither libm nor a cephes erf/erfc port bit-for-bit. Accepted (p-value). | accepted |
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| K-017 | 2026-09-28 | BAF-regression median quirk | gtc2vcf `BAFregress` (1) compares AF with the threshold as a float (0.1f), and (2) for an even number of AA/BB calls averages the quickselect result with whatever element klib `ks_ksmall` leaves just below it, not the lower middle value. Both reproduced (`--median reference`, default): 36/36 GSA samples identical to the plugin at its printed precision; `--median exact` gives the true median. SimurgArray uses autosomal sites only in pipelines; the plugin uses every VCF record. | resolved |
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| K-016 | 2026-09-28 | Sex rule of AutoCall 1.6.2.2 | Rule 1 (X heterozygosity) matches all 2141 vendor GTCs; rule 2 (X/Y intensity) differs in 12. | resolved |
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| K-015 | 2026-09-28 | Legacy GTC v3 statistics | AutoCall 1.6.2.2 writes GC10 = GC50 = 0 and #calls = #no-calls = 0 in GTC v3 (it does fill LogR dev and #intensity-only). gtc2vcf's AutoConvert 1.6.3.1 preset fills them, so this is specific to 1.6.2.x. Emulated by `--preset autocall-1.6.2`; the sample summary still reports the real statistics. | resolved; cloud re-run pending |
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| K-014 | 2026-09-28 | NaN sign | NaNs produced by libm (e.g. log2 of a negative extrapolated R) take the platform's default sign: + on aarch64, − on x86-64. SimurgArray always writes 0xFFC00000 (the reference's `-NAN`, x86 behaviour). The aarch64-built oracle differs in 1 locus of 9 GSA samples; oracle tests compare with NaNs canonicalised. | resolved |
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| K-013 | 2026-09-27 | Normalization version of public vendor GTCs | The 1000 Genomes Omni2.5 GTCs (AutoCall 1.6.2.2) are reproduced bit-for-bit by normalization 1.1.2 (109 191/109 191 bins, reserved fields included). | resolved |
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| K-012 | 2026-09-27 | FMA and bit-exactness | gcc on aarch64 contracts a*b+c into FMA by default; the gtc2vcf oracle then differs from the vendor by up to 4 ULP in some bins. Oracles are built with `-ffp-contract=off`. Any future C/Rust port (P9) must also forbid FMA contraction in exact mode. | resolved; constraint for P9 |
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| K-011 | 2026-09-27 | Plan U1 (channel order) | Infinium II X = Red, Y = Grn confirmed on 2141 vendor GTCs (the GTC PDF's "Raw X = green" wording is wrong). | resolved |
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| K-010 | 2026-09-27 | Ingest throughput | On AWS, `ingest` of 2141 Omni samples was I/O-bound (gp3 125 MB/s baseline): 18.9 min, 4 of 16 cores busy. For P9 benchmarks provision gp3 throughput or use instance-store NVMe. | open (P9) |
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| K-009 | 2026-09-27 | Missing-intensity rule | 3 loci (in 3 of 2141 vendor GTCs, AutoCall 1.6.2.2) keep one channel's intensity where we zero both. Hypothesis: old AutoCall applies the NBeads ≥ 2 rule per channel. Confirm with the bead counts of 5767788121_R01C01 (rs178512), 5826354152_R02C01 (SNP12-29082770), 6268201099_R02C01 (rs17133206); if confirmed, add a `--missing-rule per-channel` compatibility option. | open |
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| K-008 | 2026-09-27 | Vendor GTC layout | 2141 vendor GTC v3 files (AutoCall 1.6.2.2) re-encode byte-identically with the canonical v3 order, so the writer reproduces the vendor layout (no padding or reordering). | resolved |
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| K-007 | 2026-09-27 | Demo data | The "GDA v1 Demo 36" download is a GenomeStudio project (`.bsc` + `Data/*.bin`), not IDATs. The GSA v4 PGx demo (`idats_Demo_36.zip`) is used as the P0 IDAT fixture instead. Bioconductor `hapmap370k` is no longer in the current release. | resolved (plan §17 updated) |
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| K-006 | 2026-09-27 | Sample sheet | Recognised input columns (`Sample_ID`, `Sample_Name`, …) collide case-insensitively with output columns `sample_id`/`sample_name` (IN-005). Recognised columns are exempt from the reserved-name check and are passed through verbatim. | decision, revisit in P4 (OUT-060 pass-through) |
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| K-005 | 2026-09-27 | Sample sheet | Illumina's GSA v4 template sheet has an empty `Sample_Name` column → `E_SHEET_NAME_EMPTY` (IN-010 behaviour as specified). | as specified |
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| K-004 | 2026-09-27 | GTC scanner data | PMT gains are 4 bytes read as int32 by BeadArrayFiles and written as float by gtc2vcf. We keep the raw 4 bytes (byte-exact round-trip) and expose the int32 view. | resolved |
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| K-003 | 2026-09-27 | Assay type from sequences | gtc2vcf's rule for inferring Infinium I colour from probe/source sequences (needed only for BPM locus entries < v6) agrees with the explicit BPM value for 99.71 % of GSA v4 Infinium I loci. The BPM is authoritative whenever it carries the assay type. | documented; test threshold 99.5 % |
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| K-002 | 2026-09-27 | EGT data block (plan U3) | GSA v4 and GDA v1 EGTs are data-block v9 with 15 extra floats per record; the first extra float is the intensity threshold (non-zero for 16 015 GDA loci). The reader tries candidate record sizes and accepts the one whose trailing cluster counts match. The Omni2.5 EGT is dbv 7 with 15 extra floats (structure confirmed); whether its first extra float is an intensity threshold (gtc2vcf) or unused (BeadArrayFiles) is still open. | partly resolved |
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| K-001 | 2026-09-27 | IDAT MidBlock (plan U2) | In GSA v4 (BeadChip 48x4), HumanCNV370 (2x12) and 450k (12x8) IDATs the MidBlock count equals N and the section is 4 bytes per entry (int32, as in illuminaio). gtc2vcf reads uint8 but never uses the values. We infer the element size from the section length. | resolved for these chips + BeadChip 4x10 (Omni2.5, 2141 files) |
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