v2 methylation control QC (WIP): simurg methyl qc|convert-manifest (MET-001..018)

Methylation CSV manifest reader (MET-002/003), raw M/U assembly with bead masking
(MET-005), pOOBAH detection p-values, noob background correction, linear/nonlinear dye
bias, beta and M-values (MET-010..012), the 21 methylation control metrics (MET-006,
bs-conv red-bg set option), per-sample ctrl/cgs tables, summary tsv/xlsx/html with the
detection histogram and a beta PCA, pcs.tsv.gz, controls_raw/controls_qc.tsv; methylation
datasets load in qc report (MET-014); qc controls --array-type methylation; minfi-style
Sentrix_ID/Sentrix_Position sheet keys. Vendor EPIC manifests carry a 5th field on some
control lines: >= 4 fields accepted. Runs on the public minfiDataEPIC set (3 x NA12878).

Co-Authored-By: Claude Opus 5.5 <[email protected]>
Claude-Session: https://claude.ai/code/session_01814GKVzZVL3FuF3DeiZXhv

src/simurg/cli/main.py

@@ -666,6 +666,72 @@ def qc_controls_cmd(
     run_guarded(rep, lambda: run_qc_controls(opts, rep))
 
 
+# --------------------------------------------------------------------------------------------------------
+methyl_app = typer.Typer(help="Methylation arrays: control QC, detection, beta values (MET-001).")
+app.add_typer(methyl_app, name="methyl")
+
+
+@methyl_app.command("qc")
+def methyl_qc_cmd(
+    manifest: Annotated[Path, typer.Option("--manifest", help="Methylation CSV manifest (required).")],
+    out: Annotated[Path, typer.Option("--out", help="Output folder (required).")],
+    idats: Annotated[Path | None, typer.Option("--idats", help="Folder searched recursively for IDAT pairs.")] = None,
+    sheet: Annotated[Path | None, typer.Option("--sheet", help="Sample sheet (CSV).")] = None,
+    config: Annotated[Path | None, typer.Option("--config", help="QC threshold YAML.")] = None,
+    profile: Annotated[str, typer.Option("--profile", help="QC profile name, 'auto' or 'none'.")] = "auto",
+    threshold: Annotated[list[str] | None, typer.Option("--threshold", help="KEY=VALUE (repeatable).")] = None,
+    bg_offset: Annotated[float | None, typer.Option("--bg-offset", help="Background offset x (3000).")] = None,
+    bs_set: Annotated[str, typer.Option("--bs-conv-red-bg-set", help="U3-U5 (default) or U4-U6.")] = "U3-U5",
+    pval: Annotated[float, typer.Option("--pval-threshold", help="Detection p threshold.")] = 0.05,
+    beta_offset: Annotated[float, typer.Option("--beta-offset", help="alpha in M/(M+U+alpha).")] = 0.0,
+    dye_bias: Annotated[str, typer.Option("--dye-bias", help="linear|nonlinear")] = "linear",
+    min_prop: Annotated[
+        float | None, typer.Option("--min-prop-passing", help="Fail samples below this detection rate.")
+    ] = None,
+    pca_full: Annotated[int, typer.Option("--pca-max-samples-full", min=2)] = 100,
+    pca_probes: Annotated[int, typer.Option("--pca-probes", min=2)] = 10_000,
+    threads: Annotated[int, typer.Option("--threads", min=0, max=1024, help="Worker processes (0 = auto).")] = 0,
+    force: Annotated[bool, typer.Option("--force", help="Replace existing outputs.")] = False,
+    log_json: LogJson = False,
+    debug: Debug = False,
+    quiet: Quiet = False,
+) -> None:
+    """Methylation control QC: 21 control metrics, detection p-values, noob/dye-bias corrected β (MET-001)."""
+    from simurg.pipeline.methyl import MethylQcOptions, run_methyl_qc
+
+    if dye_bias not in ("linear", "nonlinear"):
+        raise typer.BadParameter("--dye-bias must be linear or nonlinear")
+    if bs_set not in ("U3-U5", "U4-U6"):
+        raise typer.BadParameter("--bs-conv-red-bg-set must be U3-U5 or U4-U6")
+    if not 0 < pval <= 1:
+        raise typer.BadParameter("--pval-threshold must be in (0, 1]")
+    rep = _reporter("methyl qc", out, log_json, debug, quiet)
+    opts = MethylQcOptions(
+        out=out, manifest=manifest, idats=idats, sheet=sheet, config=config,
+        profile=None if profile == "none" else profile, thresholds=threshold or [], bg_offset=bg_offset,
+        bs_conv_red_bg_set=bs_set, pval_threshold=pval, beta_offset=beta_offset, dye_bias=dye_bias,
+        min_prop_passing=min_prop, pca_max_samples_full=pca_full, pca_probes=pca_probes, threads=threads,
+        force=force, argv=sys.argv[1:],
+    )  # fmt: skip
+    run_guarded(rep, lambda: run_methyl_qc(opts, rep))
+
+
+@methyl_app.command("convert-manifest")
+def methyl_convert_cmd(
+    manifest: Annotated[Path, typer.Option("--manifest", help="Methylation CSV manifest (required).")],
+    out: Annotated[Path, typer.Option("--out", help="Output folder (required).")],
+    force: Annotated[bool, typer.Option("--force", help="Replace existing outputs.")] = False,
+    log_json: LogJson = False,
+    debug: Debug = False,
+    quiet: Quiet = False,
+) -> None:
+    """Methylation manifest -> probes.tsv and controls.tsv (MET-003)."""
+    from simurg.pipeline.methyl import run_convert_manifest
+
+    rep = _reporter("methyl convert-manifest", out, log_json, debug, quiet)
+    run_guarded(rep, lambda: run_convert_manifest(manifest, out, force, rep))
+
+
 def _qc_cohort(
     command: str,
     out: Path,