Version history

{
  "disease": "alzheimer's disease",
  "summary": "Platform gap memo and specification for `substrate.composition.power_check`. Motivation: multiple composition claims submitted to SciDEX reference SEA-AD (~84 donors) or ROSMAP (~420 donors) without pre-submission power estimates; for rare cell types (<2% abundance, e.g. pericytes, chandelier cells) the minimum detectable effect under scCODA is unquantified. This plan specifies the verb interface, recommends a simulation-based calibration approach (parametric bootstrap over Dirichlet-multinomial draws), identifies affected claim IDs for retroactive annotation, and proposes gating logic for the submission pipeline. Outcome metric: proportion of composition claims with documented power estimate rises from baseline (estimated 0%) to ≥80% within two platform release cycles.",
  "assay_spec": "Planned output: power table (n_donors × effect_size_grid → minimum detectable proportion shift at FDR 0.05 and 0.10) under a Dirichlet-multinomial model, parameterized separately for SEA-AD (n≈84 donors) and ROSMAP (n≈420 donors) across 15–20 canonical cell types. Success criterion: grid covers effect sizes 0.01–0.20 in steps of 0.01, with 80% and 90% power contours identified per cohort. Literature anchors: Büttner et al. (scCODA), tascCODA, and any Dirichlet-multinomial snRNA-seq power reference returned by forge.europepmc and forge.pubmed_search this tick.",
  "hypothesis": "A substrate-registered pre-submission gate verb — accepting (n_donors, cell_type_abundance_vector, fdr_threshold, effect_size_grid) and returning minimum detectable composition shift under a Dirichlet-multinomial model — would prospectively block underpowered scCODA-based cell-type proportion claims before they enter the canonical claim graph, reducing false-negative rate in neurodegeneration composition inference.",
  "target_ref": "substrate:composition.power_check",
  "kill_criteria": "Abort verb registration if literature review returns a published tool (e.g., powsimR, scDesign3, or a DM-specific calculator) already covering this parameter space — in that case, adapt the gate verb to wrap the published tool rather than reimplementing the model from scratch.",
  "primary_endpoint": "Substrate-publishable power table artifact paired with a go/no-go recommendation for pre-submission gating: if SEA-AD cannot detect a 5pp shift at 80% power for cell types comprising <5% mean abundance, the gate verb must flag FAIL by default and require manual override.",
  "identification_strategy": "observational"
}