{
  "disease_schema": "nmd-vcell-disease-evidence-module/1.0",
  "module_release": "multidisease-evidence-v0.1.0",
  "disease_id": "SMA",
  "disease_name": "Spinal muscular atrophy",
  "etiologic_anchor": "SMN1 / SMN2",
  "module_status": "NEURAL_INTERVENTION_RESPONSE_PLUS_RESIDUAL_MUSCLE",
  "analysis": {
    "module_status": "human_neural_intervention_response_plus_residual_muscle_module",
    "etiologic_anchor": "SMN1",
    "treatment_anchor": "SMN2_splicing_correction",
    "organoid_samples": 31,
    "control_lines": 3,
    "sma_lines": 2,
    "aso_treated_sma_lines": 2,
    "organoid_disease_aso_spearman_rho": 0.0987021958910337,
    "organoid_disease_aso_spearman_p": 3.075883310601733e-43,
    "organoid_genes_abs_disease_lfc05": 3509,
    "organoid_direction_consistent_reversal_fraction": 0.16557423767455115,
    "organoid_global_gene_expression_reversal": false,
    "treated_muscle_sma_samples": 8,
    "treated_muscle_control_samples": 7,
    "treated_muscle_genes_q05_abs_lfc05": 0,
    "residual_module_tests": [
      {
        "module": "Denervation",
        "p_value": 0.20492319209082033,
        "q_value": 0.3073847881362305
      },
      {
        "module": "Fibrosis",
        "p_value": 0.8133952327803173,
        "q_value": 0.8133952327803172
      },
      {
        "module": "OXPHOS",
        "p_value": 0.16393848523932633,
        "q_value": 0.3073847881362305
      }
    ],
    "neuronal_contexts": 2,
    "neuronal_replicates_per_condition": 3,
    "kif5a_effects": [
      {
        "context": "motor_neuron",
        "gene_name": "KIF5A",
        "log2FoldChange": -1.31176248640972,
        "padj": 0.0
      },
      {
        "context": "cortical_neuron",
        "gene_name": "KIF5A",
        "log2FoldChange": -1.31907142681501,
        "padj": 0.0
      }
    ],
    "cross_neuron_spearman_rho": 0.4840897259767776,
    "cross_neuron_spearman_p": 0.0,
    "source_reported_correction_axis": "SMN restoration, splicing, morphology and function in the source study",
    "reanalysis_gene_expression_axis": "no global disease-state reversal in line-aggregated bulk gene expression",
    "inference": "human_neural_disease_and_intervention_response_plus_residual_treated_muscle_no_patient_level_prediction",
    "metadata_boundary": "GSE290979 library-name descriptions swap R6-MO and scramble labels; treatment characteristics and sample titles were used.",
    "permitted_use": "neural_intervention_response_and_residual_muscle_experiment_design",
    "claim_ceiling": "no_patient_motor_outcome_prediction"
  },
  "metrics": [
    {
      "label": "Spinal organoids",
      "value": "31 samples · 3 control + 2 SMA lines"
    },
    {
      "label": "Global ASO expression reversal",
      "value": "Not observed · ρ=+0.10"
    },
    {
      "label": "Treated muscle",
      "value": "8 SMA II + 7 controls"
    },
    {
      "label": "KIF5A after SMN loss",
      "value": "−1.31 / −1.32 log2FC"
    }
  ],
  "claim_boundary": {
    "supports": [
      "human neural disease/intervention response",
      "source-reported SMN2 splicing and functional rescue",
      "KIF5A downstream mechanism",
      "residual-muscle hypotheses"
    ],
    "does_not_support": [
      "global gene-expression reversal",
      "significant OXPHOS/denervation/fibrosis module claim in this reanalysis",
      "patient motor-outcome prediction",
      "combination-therapy ranking"
    ]
  },
  "route": "/resource/disease/sma/",
  "figure": "/resource/assets/sma-evidence-module-v01.svg"
}