Methodology challenge: dataset 'SEA-AD Differential Expression: AD vs Control (MTG)' — evaluate design, statistical methods, and reproducibility.

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Description

Methodology challenge: dataset ‘SEA-AD Differential Expression: AD vs Control (MTG)’ — evaluate design, statistical methods, and reproducibility.

[TARGET_ARTIFACT type=dataset id=tabular_dataset-b3889491-fc25-440e-863d-bc96f9d33c51] [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 Differential Expression: AD vs Control (MTG) dataset’s RNA extraction protocol, sequencing method, and differential expression analysis pipeline. A passing assessment requires: (1) schema validation confirming metadata fields for donor demographics, PMI, Braak stage, CERAD score, APOE genotype, and brain region (MTG); (2) reproducibility audit confirming >=80% concordance between the dataset’s published DE gene list and independently reanalyzed raw count data using the same thresholds (|logFC| > 0.5, FDR < 0.05); (3) statistical methods review confirming appropriate library size normalization (TMM or similar), batch effect correction (ComBat or removeBatchEffect), and consensus DE gene calls across >=2 biological contrast groups. The bias_detector persona must flag any confounding variables (age, sex, PMI) before closure.

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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