# Test file for BALFSputumAssay (in vivo only)
# This assay is IN VIVO ONLY (supported_contexts: in_vivo_only)
# Samples must come from a living organism.
#
# Demonstrates per-condition outputs for a repeated-measures design: the same
# subject is sampled before exposure (experimental_group: baseline) and again
# after a controlled ozone exposure (experimental_group: treated), so the two
# records differ only in which exposure condition they were measured under.
balf_sputum_assays:
  - id: "BALF:001"
    name: "Sputum cell differential before and after controlled ozone exposure"
    has_exposure_condition:
      - id: "EXPOSURE:balf-filtered-air-2h"
        name: "Filtered air 2 hours (pre-exposure baseline visit)"
        exposure_duration:
          value: "2"
          unit:
            id: "UO:0000032"
            name: "hour"
      - id: "EXPOSURE:balf-ozone-300ppb-2h"
        name: "Ozone 0.3 ppm for 2 hours with intermittent exercise"
        exposure_agent:
          id: "CHEBI:25812"
          name: "ozone"
        exposure_concentration:
          value: "300"
          unit:
            id: "UO:0000170"
            name: "parts per billion"
        exposure_duration:
          value: "2"
          unit:
            id: "UO:0000032"
            name: "hour"
        timing_post_exposure:
          value: "24"
          unit:
            id: "UO:0000032"
            name: "hour"
    has_specified_output:
      - id: "BALF:001-output-baseline"
        name: "Pre-exposure baseline sputum measurements"
        experimental_group: baseline
        measured_under: "EXPOSURE:balf-filtered-air-2h"
        neutrophil_percentage:
          value: "24.0"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        il8_concentration:
          value: "95"
          unit:
            id: "UO:0010070"
            name: "picogram per milliliter"
          central_tendency: single_value
          sample_size: 1
        eosinophil_percentage:
          value: "3.1"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        macrophage_percentage:
          value: "58.0"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        lymphocyte_percentage:
          value: "14.9"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        total_cell_count:
          value: "1400000"
          unit:
            id: "UO:0000201"
            name: "cells per milliliter"
          central_tendency: single_value
          sample_size: 1
        il6_concentration:
          value: "32"
          unit:
            id: "UO:0010070"
            name: "picogram per milliliter"
          central_tendency: single_value
          sample_size: 1
        tnf_alpha_concentration:
          value: "48"
          unit:
            id: "UO:0010070"
            name: "picogram per milliliter"
          central_tendency: single_value
          sample_size: 1
        total_protein_concentration:
          value: "0.7"
          unit:
            id: "UO:0000176"
            name: "milligram per milliliter"
          central_tendency: single_value
          sample_size: 1
      - id: "BALF:001-output-ozone"
        name: "24-hour post-ozone sputum measurements"
        experimental_group: treated
        measured_under: "EXPOSURE:balf-ozone-300ppb-2h"
        neutrophil_percentage:
          value: "45.0"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        il8_concentration:
          value: "250"
          unit:
            id: "UO:0010070"
            name: "picogram per milliliter"
          central_tendency: single_value
          sample_size: 1
        eosinophil_percentage:
          value: "3.5"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        macrophage_percentage:
          value: "38.0"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        lymphocyte_percentage:
          value: "12.5"
          unit:
            id: "UO:0000187"
            name: "percent"
          central_tendency: single_value
          sample_size: 1
        total_cell_count:
          value: "2500000"
          unit:
            id: "UO:0000201"
            name: "cells per milliliter"
          central_tendency: single_value
          sample_size: 1
        il6_concentration:
          value: "85"
          unit:
            id: "UO:0010070"
            name: "picogram per milliliter"
          central_tendency: single_value
          sample_size: 1
        tnf_alpha_concentration:
          value: "120"
          unit:
            id: "UO:0010070"
            name: "picogram per milliliter"
          central_tendency: single_value
          sample_size: 1
        total_protein_concentration:
          value: "1.2"
          unit:
            id: "UO:0000176"
            name: "milligram per milliliter"
          central_tendency: single_value
          sample_size: 1
    assay_date: "2024-07-22"
    informs_on_key_event:
      id: "KE:ke-airway-inflammation"
      name: "Airway inflammation"
      biological_action: increased
      level_of_biological_organization: tissue
    target_cell_type:
      id: "CL:0000775"
      name: "neutrophil"
    study_subject:
      subject_type: InVivoSubject
      id: "SUBJECT:001"
      name: "Subject A"
      model_species:
        id: "NCBITaxon:9606"
        name: "Homo sapiens"
      age:
        value: "45"
        unit:
          id: "UO:0000036"
          name: "year"
      sex: "female"
      sample_type: sputum
      collection_site: "pulmonary clinic"
      subject_characteristics: "Non-smoker, mild asthma"
      sample_collection_method: "Induced sputum with hypertonic saline nebulization"
      clinical_context: "Controlled ozone exposure study, stable asthma at enrollment"
    follows_protocols:
      - protocol_type: MolecularAssayProtocol
        id: "PROTOCOL:balf-001"
        name: "Sputum cell differential protocol"
        detection_method: "cytospin and Diff-Quik staining"

# Analysis layer: within-subject changes from the pre-exposure baseline. Cell
# differentials are percentages, so their change is an absolute difference in
# percentage points; IL-8 is expressed as a percent change from baseline.
response_comparisons:
  - id: "COMP:BALF001-neutrophil-percentage"
    name: "Change in sputum neutrophil percentage, post-ozone vs baseline"
    derived_from_assay: "BALF:001"
    compared_measurement: "neutrophil_percentage"
    control_output: "BALF:001-output-baseline"
    treated_output: "BALF:001-output-ozone"
    change_type: absolute_difference
    change_direction: increased
    change_value:
      value: "21.0"
      unit:
        id: "UO:0000187"
        name: "percent"
    derivation: computed
  - id: "COMP:BALF001-il8"
    name: "Change in sputum IL-8 concentration, post-ozone vs baseline"
    derived_from_assay: "BALF:001"
    compared_measurement: "il8_concentration"
    control_output: "BALF:001-output-baseline"
    treated_output: "BALF:001-output-ozone"
    change_type: percent_change
    change_direction: increased
    change_value:
      value: "163.2"
      unit:
        id: "UO:0000187"
        name: "percent"
    derivation: computed