Methodology challenge: dataset 'Allen Brain SEA-AD MTG 10x snRNA-seq' — evaluate design, statistical methods, and reproducibility.

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Description

Methodology challenge: dataset ‘Allen Brain SEA-AD MTG 10x snRNA-seq’ — evaluate design, statistical methods, and reproducibility.

[TARGET_ARTIFACT type=dataset id=dataset-192467e0-fe96-43cb-a64f-e891cdcff111] [DEBATE_TYPE methodology_challenge] [PERSONAS provenance_auditor,bias_detector,schema_validator] [NUM_ROUNDS 4] [AUTO_TRIGGER rule=notebook_debate_scheduler]

Resolution criteria

Resolved when the provenance_auditor persona certifies the SEA-AD MTG 10x snRNA-seq dataset’s cell isolation protocol, library preparation kit, sequencing platform, and computational pipeline (cell ranger vs outro), and the bias_detector persona identifies any batch effects, population stratification issues, or confounding variables. A passing assessment requires: (1) schema validation confirming metadata fields for donor age, sex, PMI, APOE status, clinical diagnosis, and brain region; (2) reproducibility audit confirming >=80% overlap between published marker gene lists (APP, MAPT, GFAP, CLU) and dataset’s top 20 differentially expressed genes; (3) statistical methods review confirming appropriate multiple-testing correction (FDR < 0.05) and minimum biological replicate count (n >= 3 donors per group). The gap closes when a methodologist-signed artifact records these validations with quantitative thresholds and links to the source dataset in the KG.

Evidence summary

Resolved by hypothesis h-5b378bd3: TREM2-APOE Axis Dissociation for Selective DAM Activation. Score: 0.886. Supporting PMIDs: 28930663, 30617257.

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