opencode-knowledge-work 0.0.0-stage → 0.1.1

package/content/bio-research/skills/bio-research-instrument-data-to-allotrope/scripts/validate_asm.py

@@ -0,0 +1,1102 @@
+#!/usr/bin/env python3
+"""
+ASM Output Validation Script
+
+Validates ASM JSON output against common issues:
+- Wrong technique selection
+- Hyphenated field names (should be space-separated)
+- Missing statistics documents
+- Incorrect units
+- Missing required fields
+- Missing calculated data traceability
+- Improperly flattened nested documents (sample document, device control, etc.)
+
+Validation Rules:
+    Based on: Allotrope ASM specification (December 2024)
+    Last Updated: 2026-01-07
+    Source: https://gitlab.com/allotrope-public/asm/-/tree/main/json-schemas/adm
+
+Note: Unknown techniques/units generate WARNINGS (not errors) to allow for new
+additions to the Allotrope specification. This prevents blocking valid data
+when the Allotrope foundation adds new techniques or units.
+
+Usage:
+    python validate_asm.py output.json
+    python validate_asm.py output.json --reference reference.json
+    python validate_asm.py output.json --strict
+"""
+
+import json
+import re
+import sys
+import argparse
+from typing import Dict, List, Tuple, Any, Optional
+
+# Validation metadata
+ASM_SPEC_VERSION = "2024-12"
+VALIDATION_RULES_DATE = "2026-01-07"
+SCHEMA_SOURCE = "https://gitlab.com/allotrope-public/asm"
+
+
+# All valid ASM techniques from https://gitlab.com/allotrope-public/asm/-/tree/main/json-schemas/adm
+VALID_TECHNIQUES = [
+    "absorbance",
+    "automated-reactors",
+    "balance",
+    "bga",
+    "binding-affinity",
+    "bulk-density",
+    "cell-counting",
+    "cell-culture-analyzer",
+    "chromatography",
+    "code-reader",
+    "conductance",
+    "conductivity",
+    "disintegration",
+    "dsc",
+    "dvs",
+    "electronic-lab-notebook",
+    "electronic-spectrometry",
+    "electrophoresis",
+    "flow-cytometry",
+    "fluorescence",
+    "foam-height",
+    "foam-qualification",
+    "fplc",
+    "ftir",
+    "gas-chromatography",
+    "gc-ms",
+    "gloss",
+    "hot-tack",
+    "impedance",
+    "lc-ms",
+    "light-obscuration",
+    "liquid-chromatography",
+    "liquid-handler",  # Added for liquid handler support
+    "loss-on-drying",
+    "luminescence",
+    "mass-spectrometry",
+    "metabolite-analyzer",
+    "multi-analyte-profiling",
+    "nephelometry",
+    "nmr",
+    "optical-imaging",
+    "optical-microscopy",
+    "osmolality",
+    "oven-kf",
+    "pcr",
+    "ph",
+    "plate-reader",
+    "pressure-monitoring",
+    "psd",
+    "pumping",
+    "raman",
+    "rheometry",
+    "sem",
+    "solution-analyzer",
+    "specific-rotation",
+    "spectrophotometry",
+    "stirring",
+    "surface-area-analysis",
+    "tablet-hardness",
+    "temperature-monitoring",
+    "tensile-test",
+    "thermogravimetric-analysis",
+    "titration",
+    "ultraviolet-absorbance",
+    "x-ray-powder-diffraction",
+]
+
+# Instrument keywords that indicate specific techniques
+TECHNIQUE_INDICATORS = {
+    "multi-analyte-profiling": [
+        "bead",
+        "luminex",
+        "bio-plex",
+        "bioplex",
+        "multiplex",
+        "plex",
+        "msd",
+        "region",
+    ],
+    "electrophoresis": [
+        "tapestation",
+        "bioanalyzer",
+        "labchip",
+        "fragment",
+        "din",
+        "rin",
+        "gel",
+        "capillary",
+    ],
+    "spectrophotometry": ["nanodrop", "lunatic", "a260", "a280", "wavelength"],
+    "cell-counting": [
+        "viability",
+        "viable cell",
+        "cell count",
+        "vi-cell",
+        "vicell",
+        "nucleocounter",
+        "cell density",
+    ],
+    "pcr": [
+        "ct",
+        "quantstudio",
+        "cfx",
+        "amplification",
+        "melt curve",
+        "qpcr",
+        "cycle threshold",
+    ],
+    "plate-reader": [
+        "microplate",
+        "96-well",
+        "384-well",
+        "plate reader",
+        "envision",
+        "spectramax",
+    ],
+    "liquid-chromatography": [
+        "hplc",
+        "uplc",
+        "retention time",
+        "chromatogram",
+        "empower",
+        "chromeleon",
+    ],
+    "flow-cytometry": ["facs", "flow cytometry", "scatter", "gating", "cytometer"],
+    "mass-spectrometry": ["m/z", "mass spec", "ms/ms", "lcms", "maldi"],
+    "fluorescence": ["fluorescence", "excitation", "emission", "fluorimeter"],
+    "luminescence": ["luminescence", "bioluminescence", "chemiluminescence"],
+    "absorbance": ["absorbance", "optical density", "od600"],
+    "ph": ["ph meter", "ph measurement"],
+    "osmolality": ["osmolality", "osmometer"],
+    "conductivity": ["conductivity", "conductance"],
+    "balance": ["balance", "weight", "mass measurement"],
+    "nmr": ["nmr", "nuclear magnetic resonance"],
+    "ftir": ["ftir", "infrared", "ir spectrum"],
+    "raman": ["raman", "raman spectroscopy"],
+    "liquid-handler": [
+        "biomek",
+        "liquid handler",
+        "aspirate",
+        "dispense",
+        "transfer volume",
+        "liquid handling",
+    ],
+}
+
+# Fields that should typically be in calculated-data-document, not measurement-document
+SHOULD_BE_CALCULATED = [
+    "dna integrity number",
+    "rna integrity number",
+    "din",
+    "rin",
+    "viability",
+    "260/280",
+    "a260/a280",
+    "concentration",  # When derived from standard curve
+    "percent of total",
+    "average size",
+    "molarity",  # When calculated from concentration
+    "relative quantity",
+    "fold change",
+    "coefficient of variation",
+]
+
+# =============================================================================
+# NESTED DOCUMENT STRUCTURE DEFINITIONS
+# =============================================================================
+
+# Fields that MUST be inside 'sample document' (space or hyphen separated)
+SAMPLE_DOCUMENT_FIELDS = {
+    # Core sample identification
+    "sample identifier",
+    "sample-identifier",
+    "written name",
+    "written-name",
+    "batch identifier",
+    "batch-identifier",
+    "sample role type",
+    "sample-role-type",
+    "description",
+    # Location fields (should be in sample document for most techniques)
+    "location identifier",
+    "location-identifier",
+    "well location identifier",
+    "well-location-identifier",
+    "well plate identifier",
+    "well-plate-identifier",
+    # Liquid handler specific - source/destination pairs
+    "source location identifier",
+    "source-location-identifier",
+    "destination location identifier",
+    "destination-location-identifier",
+    "source well plate identifier",
+    "source-well-plate-identifier",
+    "destination well plate identifier",
+    "destination-well-plate-identifier",
+    "source well location identifier",
+    "source-well-location-identifier",
+    "destination well location identifier",
+    "destination-well-location-identifier",
+}
+
+# Fields that MUST be inside 'device control aggregate document' -> 'device control document'
+DEVICE_CONTROL_FIELDS = {
+    # General device control
+    "device type",
+    "device-type",
+    "detector wavelength setting",
+    "detector-wavelength-setting",
+    "compartment temperature",
+    "compartment-temperature",
+    "sample volume setting",
+    "sample-volume-setting",
+    "flow rate",
+    "flow-rate",
+    "exposure duration setting",
+    "exposure-duration-setting",
+    "detector gain setting",
+    "detector-gain-setting",
+    "illumination setting",
+    "illumination-setting",
+    # Liquid handler specific
+    "liquid handling technique",
+    "liquid-handling-technique",
+    "source liquid handling technique",
+    "source-liquid-handling-technique",
+    "destination liquid handling technique",
+    "destination-liquid-handling-technique",
+}
+
+# Fields that should be in 'custom information document' (vendor-specific)
+CUSTOM_INFO_FIELDS = {
+    # Liquid handler specific
+    "probe",
+    "pod",
+    "source labware name",
+    "source-labware-name",
+    "destination labware name",
+    "destination-labware-name",
+    "deck position",
+    "deck-position",
+}
+
+# Fields that commonly get incorrectly flattened (superset for general checking)
+COMMONLY_FLATTENED_FIELDS = {
+    # Sample-related (often incorrectly put directly on measurement)
+    "sample identifier",
+    "sample-identifier",
+    "sample barcode",
+    "sample-barcode",
+    "well index",
+    "well-index",
+    "location identifier",
+    "location-identifier",
+    # Device control related (often incorrectly put directly on measurement)
+    "probe identifier",
+    "probe-identifier",
+    "device identifier",  # When it should be in device control doc, not measurement
+    "device-identifier",
+    "technique",  # Should be "liquid handling technique" in device control
+    "transfer type",  # Should be structured differently
+    "transfer-type",
+}
+
+# Standard ASM units
+VALID_UNITS = {
+    "fluorescence": ["RFU", "MFI", "(unitless)"],
+    "counts": ["#"],
+    "volume": ["μL", "mL", "L", "µL"],
+    "concentration": [
+        "ng/μL",
+        "ng/mL",
+        "pg/mL",
+        "mg/mL",
+        "μg/mL",
+        "M",
+        "mM",
+        "μM",
+        "nM",
+    ],
+    "temperature": ["degC"],
+    "unitless": ["(unitless)", "%"],
+    "molecular_weight": ["bp", "Da", "kDa"],
+    "time": ["s", "min", "h"],
+}
+
+# Standard sample role types
+VALID_SAMPLE_ROLES = [
+    "standard sample role",
+    "blank role",
+    "control sample role",
+    "unknown sample role",
+    "reference sample role",
+    "calibration sample role",
+]
+
+# Standard statistic datum roles
+VALID_STATISTIC_ROLES = [
+    "median role",
+    "arithmetic mean role",
+    "coefficient of variation role",
+    "standard deviation role",
+    "standard error role",
+    "trimmed arithmetic mean role",
+    "trimmed standard deviation role",
+    "minimum value role",
+    "maximum value role",
+]
+
+
+class ValidationResult:
+    """Container for validation results."""
+
+    def __init__(self):
+        self.errors: List[str] = []
+        self.warnings: List[str] = []
+        self.info: List[str] = []
+        self.metrics: Dict[str, Any] = {}
+
+    def add_error(self, msg: str):
+        self.errors.append(f"ERROR: {msg}")
+
+    def add_warning(self, msg: str):
+        self.warnings.append(f"WARNING: {msg}")
+
+    def add_info(self, msg: str):
+        self.info.append(f"INFO: {msg}")
+
+    def is_valid(self) -> bool:
+        return len(self.errors) == 0
+
+    def print_report(self):
+        print("\n" + "=" * 60)
+        print("ASM VALIDATION REPORT")
+        print("=" * 60)
+
+        # Print metrics
+        if self.metrics:
+            print("\nMetrics:")
+            for key, value in self.metrics.items():
+                print(f"   {key}: {value}")
+
+        # Print info
+        if self.info:
+            print("\n" + "\n".join(self.info))
+
+        # Print warnings
+        if self.warnings:
+            print("\n" + "\n".join(self.warnings))
+
+        # Print errors
+        if self.errors:
+            print("\n" + "\n".join(self.errors))
+
+        # Summary
+        print("\n" + "-" * 60)
+        if self.is_valid():
+            if self.warnings:
+                print(f"PASSED with {len(self.warnings)} warning(s)")
+            else:
+                print("PASSED - No issues found")
+        else:
+            print(
+                f"FAILED - {len(self.errors)} error(s), {len(self.warnings)} warning(s)"
+            )
+        print("=" * 60 + "\n")
+
+
+def validate_manifest(asm: Dict, result: ValidationResult):
+    """Check for valid manifest."""
+    if "$asm.manifest" not in asm:
+        result.add_error("Missing $asm.manifest")
+        return
+
+    manifest = asm["$asm.manifest"]
+    if isinstance(manifest, str):
+        if "allotrope.org" in manifest:
+            result.add_info(f"Manifest: {manifest}")
+        else:
+            result.add_warning(f"Non-standard manifest URL: {manifest}")
+    elif isinstance(manifest, dict):
+        if "vocabulary" in manifest or "contexts" in manifest:
+            result.add_info("Manifest: Object format with vocabulary/contexts")
+        else:
+            result.add_warning("Manifest object missing vocabulary or contexts")
+
+
+def detect_technique(asm: Dict) -> Tuple[str, float]:
+    """Detect technique from ASM structure."""
+    # Check for technique in top-level keys
+    for key in asm.keys():
+        if key == "$asm.manifest":
+            continue
+        # Extract technique name from aggregate document key
+        # Handle both "liquid handler aggregate document" and "liquid-handler-aggregate-document"
+        key_normalized = key.lower().replace("-", " ")
+        if "aggregate document" in key_normalized:
+            technique = key_normalized.replace(" aggregate document", "").strip()
+            return technique, 100.0
+
+    return "unknown", 0.0
+
+
+def validate_technique(asm: Dict, result: ValidationResult, content_str: str):
+    """Validate technique selection."""
+    technique, confidence = detect_technique(asm)
+    result.metrics["technique"] = technique
+    result.metrics["technique_confidence"] = confidence
+
+    if technique == "unknown":
+        result.add_warning("Could not detect technique from ASM structure")
+        return
+
+    result.add_info(f"Detected technique: {technique}")
+
+    # Check if technique is in known list (soft validation)
+    technique_normalized = technique.replace(" ", "-")
+    if technique_normalized not in VALID_TECHNIQUES:
+        result.add_warning(
+            f"Unknown technique '{technique}' not in known list (as of {VALIDATION_RULES_DATE}). "
+            f"This may be a new Allotrope addition. Verify at: {SCHEMA_SOURCE}"
+        )
+
+    # Check if technique seems appropriate for content
+    content_lower = content_str.lower()
+    suggested_technique = None
+
+    for tech, keywords in TECHNIQUE_INDICATORS.items():
+        matches = sum(1 for kw in keywords if kw in content_lower)
+        if matches >= 2:  # Multiple keyword matches
+            if tech != technique.replace(" ", "-"):
+                suggested_technique = tech
+                break
+
+    if suggested_technique:
+        result.add_warning(
+            f"Content suggests '{suggested_technique}' but ASM uses '{technique}' - "
+            "verify correct technique selection"
+        )
+
+
+def validate_naming_conventions(content_str: str, result: ValidationResult):
+    """Check for proper space-separated naming (not hyphens)."""
+    # Find all keys that look like ASM field names
+    # Hyphenated keys in ASM are typically wrong (should be space-separated)
+    hyphenated_keys = re.findall(r'"([a-z]+-[a-z]+-?[a-z]*-?[a-z]*)":', content_str)
+
+    # Filter to likely ASM fields (not URLs, not manifest)
+    asm_hyphenated = []
+    for key in hyphenated_keys:
+        if "http" in key or "manifest" in key:
+            continue
+        # Known hyphenated keys that are OK
+        if key in ["data-source-identifier", "data-source-feature"]:
+            continue
+        asm_hyphenated.append(key)
+
+    if asm_hyphenated:
+        unique = list(set(asm_hyphenated))[:10]
+        result.add_warning(
+            f"Found hyphenated field names (ASM uses spaces): {unique}"
+            + (" ... and more" if len(set(asm_hyphenated)) > 10 else "")
+        )
+        result.add_info("Tip: Use 'sample identifier' not 'sample-identifier'")
+
+
+def count_measurements(content_str: str) -> int:
+    """Count measurement documents in ASM."""
+    # Count occurrences of measurement document patterns
+    count = len(re.findall(r'"measurement identifier":', content_str))
+    if count == 0:
+        count = len(re.findall(r'"measurement-identifier":', content_str))
+    return count
+
+
+def validate_measurements(content_str: str, result: ValidationResult):
+    """Validate measurement documents."""
+    count = count_measurements(content_str)
+    result.metrics["measurement_count"] = count
+
+    if count == 0:
+        result.add_warning("No measurement documents found")
+    else:
+        result.add_info(f"Measurement count: {count}")
+
+
+def validate_sample_roles(content_str: str, result: ValidationResult):
+    """Check for valid sample roles."""
+    roles = re.findall(r'"sample.role.type":\s*"([^"]+)"', content_str)
+    if not roles:
+        roles = re.findall(r'"sample role type":\s*"([^"]+)"', content_str)
+
+    if roles:
+        unknown_roles = [r for r in set(roles) if r not in VALID_SAMPLE_ROLES]
+        if unknown_roles:
+            result.add_warning(
+                f"Unknown sample roles not in known list (as of {VALIDATION_RULES_DATE}): {unknown_roles}. "
+                f"These may be valid Allotrope roles added after spec version {ASM_SPEC_VERSION}. "
+                f"Verify at: {SCHEMA_SOURCE}"
+            )
+
+
+def validate_statistics(asm: Dict, content_str: str, result: ValidationResult):
+    """Check for statistics documents where expected."""
+    technique, _ = detect_technique(asm)
+
+    has_stats = (
+        "statistics aggregate document" in content_str.lower()
+        or "statistics-aggregate-document" in content_str
+    )
+
+    result.metrics["has_statistics"] = has_stats
+
+    # Statistics are required for multi-analyte profiling
+    if "multi analyte" in technique or "multiplex" in content_str.lower():
+        if not has_stats:
+            result.add_warning(
+                "No statistics aggregate document found - bead-based assays should include "
+                "median, mean, CV, std dev per analyte"
+            )
+        else:
+            result.add_info("Statistics document: Present")
+
+
+def validate_units(content_str: str, result: ValidationResult):
+    """Check for valid units."""
+    # Find all unit values
+    units = re.findall(r'"unit":\s*"([^"]+)"', content_str)
+
+    # Check for common case-sensitivity issues
+    case_issues = []
+    for unit in set(units):
+        if unit.lower() in ["rfu", "mfi"] and unit not in ["RFU", "MFI"]:
+            case_issues.append(f"{unit} (should be uppercase)")
+        elif unit in ["ul", "uL", "µl"] and unit != "μL":
+            case_issues.append(f"{unit} (should be μL)")
+
+    if case_issues:
+        result.add_warning(f"Non-standard unit capitalization: {case_issues}")
+
+    # Soft validation: check against known units list
+    all_known_units = set()
+    for unit_list in VALID_UNITS.values():
+        all_known_units.update(unit_list)
+
+    unknown_units = []
+    for unit in set(units):
+        # Skip units that have case issues (already reported above)
+        if unit not in all_known_units and unit not in [u.lower() for u in case_issues]:
+            unknown_units.append(unit)
+
+    if unknown_units:
+        result.add_warning(
+            f"Unknown units not in known list (as of {VALIDATION_RULES_DATE}): {unknown_units}. "
+            f"These may be valid Allotrope units added after spec version {ASM_SPEC_VERSION}. "
+            f"Verify at: {SCHEMA_SOURCE}"
+        )
+
+
+def validate_metadata(content_str: str, result: ValidationResult):
+    """Check for required metadata fields."""
+    required_fields = [
+        ("device system document", "equipment serial number"),
+        ("data system document", "software name"),
+        ("data system document", "software version"),
+    ]
+
+    missing = []
+    for _, field in required_fields:
+        if (
+            field not in content_str.lower()
+            and field.replace(" ", "-") not in content_str
+        ):
+            missing.append(field)
+
+    if missing:
+        result.add_warning(f"Missing recommended metadata: {missing}")
+
+
+def validate_calculated_data(content_str: str, result: ValidationResult):
+    """Check calculated data has proper traceability."""
+    content_lower = content_str.lower()
+
+    has_calculated = (
+        "calculated data document" in content_lower
+        or "calculated-data-document" in content_str
+    )
+    has_data_source = (
+        "data source aggregate document" in content_lower
+        or "data-source-aggregate-document" in content_str
+    )
+
+    result.metrics["has_calculated_data"] = has_calculated
+    result.metrics["has_data_source_traceability"] = has_data_source
+
+    if has_calculated:
+        result.add_info("Calculated data document: Present")
+        if not has_data_source:
+            result.add_error(
+                "Calculated data found without data-source-aggregate-document - "
+                "traceability is required for audit/regulatory compliance"
+            )
+        else:
+            result.add_info("Data source traceability: Present")
+
+    # Check for calculated fields that might be incorrectly placed in measurement-document
+    misplaced = []
+    for field in SHOULD_BE_CALCULATED:
+        # Check if field appears in measurement document context but not in calculated data
+        field_pattern = field.replace("/", ".")
+        if field_pattern in content_lower:
+            # If we have the field but no calculated-data-document, it's misplaced
+            if not has_calculated:
+                misplaced.append(field)
+
+    if misplaced:
+        result.add_warning(
+            f"Fields that should likely be in calculated-data-document: {misplaced[:5]}"
+            + (f" ... and {len(misplaced)-5} more" if len(misplaced) > 5 else "")
+        )
+
+
+def validate_unique_identifiers(content_str: str, result: ValidationResult):
+    """Validate that entities have unique identifiers for traceability."""
+    # Count different identifier types
+    measurement_ids = len(
+        re.findall(r'"measurement identifier":\s*"[^"]+"', content_str)
+    )
+    if measurement_ids == 0:
+        measurement_ids = len(
+            re.findall(r'"measurement-identifier":\s*"[^"]+"', content_str)
+        )
+
+    calculated_ids = len(
+        re.findall(r'"calculated data identifier":\s*"[^"]+"', content_str)
+    )
+    if calculated_ids == 0:
+        calculated_ids = len(
+            re.findall(r'"calculated-data-identifier":\s*"[^"]+"', content_str)
+        )
+
+    data_source_ids = len(
+        re.findall(r'"data source identifier":\s*"[^"]+"', content_str)
+    )
+    if data_source_ids == 0:
+        data_source_ids = len(
+            re.findall(r'"data-source-identifier":\s*"[^"]+"', content_str)
+        )
+
+    result.metrics["measurement_identifiers"] = measurement_ids
+    result.metrics["calculated_data_identifiers"] = calculated_ids
+    result.metrics["data_source_identifiers"] = data_source_ids
+
+    if measurement_ids == 0:
+        result.add_warning(
+            "No measurement identifiers found - required for traceability"
+        )
+
+    # If we have calculated data but no data source identifiers, that's a problem
+    if calculated_ids > 0 and data_source_ids == 0:
+        result.add_error(
+            f"Found {calculated_ids} calculated data entries but no data source identifiers - "
+            "each calculated value should reference its source"
+        )
+
+
+# =============================================================================
+# NEW: NESTED DOCUMENT STRUCTURE VALIDATION
+# =============================================================================
+
+
+def validate_nested_document_structure(
+    asm: Dict, content_str: str, result: ValidationResult
+):
+    """
+    Validate that fields are properly nested in their correct documents.
+
+    This checks for common mistakes like:
+    - Sample fields flattened directly onto measurement instead of in 'sample document'
+    - Device control fields flattened instead of in 'device control aggregate document'
+    - Custom/vendor fields not wrapped in 'custom information document'
+    """
+    content_lower = content_str.lower()
+
+    # Check if proper nested documents exist
+    has_sample_doc = (
+        '"sample document"' in content_lower or '"sample-document"' in content_str
+    )
+    has_device_control_doc = (
+        '"device control aggregate document"' in content_lower
+        or '"device-control-aggregate-document"' in content_str
+    )
+    has_custom_info_doc = (
+        '"custom information document"' in content_lower
+        or '"custom-information-document"' in content_str
+    )
+
+    result.metrics["has_sample_document"] = has_sample_doc
+    result.metrics["has_device_control_document"] = has_device_control_doc
+    result.metrics["has_custom_information_document"] = has_custom_info_doc
+
+    # Parse ASM to check field locations
+    def find_flattened_fields_in_measurements(obj, path=""):
+        """Recursively find fields that appear directly on measurement documents."""
+        issues = {"sample": [], "device_control": [], "custom": []}
+
+        if isinstance(obj, dict):
+            # Check if we're inside a measurement document
+            in_measurement = (
+                "measurement document" in path.lower() or "measurement-document" in path
+            )
+            in_sample_doc = (
+                "sample document" in path.lower() or "sample-document" in path
+            )
+            in_device_control = (
+                "device control" in path.lower() or "device-control" in path
+            )
+            in_custom_info = (
+                "custom information" in path.lower() or "custom-information" in path
+            )
+
+            for key, value in obj.items():
+                key_normalized = key.lower().replace("-", " ")
+                new_path = f"{path}.{key}"
+
+                # Check if this key should be nested but isn't
+                if in_measurement and not in_sample_doc:
+                    if key_normalized in [
+                        f.lower().replace("-", " ") for f in SAMPLE_DOCUMENT_FIELDS
+                    ]:
+                        issues["sample"].append(key)
+
+                if in_measurement and not in_device_control:
+                    if key_normalized in [
+                        f.lower().replace("-", " ") for f in DEVICE_CONTROL_FIELDS
+                    ]:
+                        issues["device_control"].append(key)
+
+                if in_measurement and not in_custom_info:
+                    if key_normalized in [
+                        f.lower().replace("-", " ") for f in CUSTOM_INFO_FIELDS
+                    ]:
+                        issues["custom"].append(key)
+
+                # Recurse
+                child_issues = find_flattened_fields_in_measurements(value, new_path)
+                for k in issues:
+                    issues[k].extend(child_issues[k])
+
+        elif isinstance(obj, list):
+            for i, item in enumerate(obj):
+                child_issues = find_flattened_fields_in_measurements(
+                    item, f"{path}[{i}]"
+                )
+                for k in issues:
+                    issues[k].extend(child_issues[k])
+
+        return issues
+
+    issues = find_flattened_fields_in_measurements(asm)
+    flattened_sample_fields = list(set(issues["sample"]))
+    flattened_device_control_fields = list(set(issues["device_control"]))
+    flattened_custom_fields = list(set(issues["custom"]))
+
+    # Report issues
+    if flattened_sample_fields:
+        result.add_error(
+            f"Fields that should be nested in 'sample document' are flattened on measurement: "
+            f"{flattened_sample_fields[:5]}"
+            + (
+                f" ... and {len(flattened_sample_fields)-5} more"
+                if len(flattened_sample_fields) > 5
+                else ""
+            )
+        )
+        result.add_info(
+            "Tip: Wrap sample fields in a 'sample document' object inside each measurement"
+        )
+
+    if flattened_device_control_fields:
+        result.add_error(
+            f"Fields that should be nested in 'device control aggregate document' are flattened: "
+            f"{flattened_device_control_fields[:5]}"
+            + (
+                f" ... and {len(flattened_device_control_fields)-5} more"
+                if len(flattened_device_control_fields) > 5
+                else ""
+            )
+        )
+        result.add_info(
+            "Tip: Wrap device control fields in 'device control aggregate document' → 'device control document'"
+        )
+
+    if flattened_custom_fields:
+        result.add_warning(
+            f"Vendor-specific fields that should be in 'custom information document': "
+            f"{flattened_custom_fields[:5]}"
+            + (
+                f" ... and {len(flattened_custom_fields)-5} more"
+                if len(flattened_custom_fields) > 5
+                else ""
+            )
+        )
+
+
+def validate_liquid_handler_structure(
+    asm: Dict, content_str: str, result: ValidationResult
+):
+    """
+    Specific validation for liquid handler ASM documents.
+
+    Checks for:
+    - Proper transfer pairing (aspirate + dispense = 1 measurement)
+    - Source/destination field pairs
+    - Aspiration volume + transfer volume instead of single volume
+    """
+    technique, _ = detect_technique(asm)
+
+    # Only run for liquid handler techniques
+    if "liquid" not in technique.lower() and "handler" not in technique.lower():
+        # Also check content for liquid handler indicators
+        content_lower = content_str.lower()
+        if not any(
+            kw in content_lower
+            for kw in ["aspirate", "dispense", "liquid handler", "biomek"]
+        ):
+            return
+
+    result.add_info("Liquid handler specific validation...")
+
+    content_lower = content_str.lower()
+
+    # Check for proper volume field structure
+    has_aspiration_volume = (
+        "aspiration volume" in content_lower or "aspiration-volume" in content_str
+    )
+    has_transfer_volume = (
+        "transfer volume" in content_lower or "transfer-volume" in content_str
+    )
+    has_single_volume = (
+        '"volume"' in content_str
+        and not has_aspiration_volume
+        and not has_transfer_volume
+    )
+
+    if has_single_volume and not has_aspiration_volume:
+        result.add_warning(
+            "Liquid handler ASM uses single 'volume' field - "
+            "consider using 'aspiration volume' and 'transfer volume' for full transfer semantics"
+        )
+
+    if has_aspiration_volume and has_transfer_volume:
+        result.add_info("Volume fields: Proper aspiration/transfer volume structure")
+
+    # Check for source/destination pairing
+    has_source_dest = (
+        "source location" in content_lower or "source-location" in content_str
+    ) and (
+        "destination location" in content_lower or "destination-location" in content_str
+    )
+
+    has_separate_transfer_type = (
+        "transfer type" in content_lower or "transfer-type" in content_str
+    )
+
+    if has_separate_transfer_type and not has_source_dest:
+        result.add_warning(
+            "Found 'transfer type' field (Aspirate/Dispense as separate records) - "
+            "proper ASM pairs source→destination in single measurement with 'source location identifier' "
+            "and 'destination location identifier'"
+        )
+        result.add_info(
+            "Tip: Pair aspirate+dispense operations by probe number into single transfer measurements"
+        )
+
+    if has_source_dest:
+        result.add_info("Source/destination: Proper paired transfer structure")
+
+    # Check for labware name fields in custom information document
+    has_labware_names = (
+        "source labware name" in content_lower
+        or "destination labware name" in content_lower
+    )
+
+    if has_labware_names:
+        result.add_info(
+            "Labware names: Present (should be in custom information document)"
+        )
+
+
+def compare_to_reference(
+    asm: Dict,
+    reference: Dict,
+    content_str: str,
+    ref_content: str,
+    result: ValidationResult,
+):
+    """Compare generated ASM to reference ASM."""
+    result.add_info("Comparing to reference ASM...")
+
+    # Compare techniques
+    gen_tech, _ = detect_technique(asm)
+    ref_tech, _ = detect_technique(reference)
+
+    if gen_tech.replace("-", " ") != ref_tech.replace("-", " "):
+        result.add_error(
+            f"Technique mismatch: generated '{gen_tech}' vs reference '{ref_tech}'"
+        )
+
+    # Compare measurement counts
+    gen_count = count_measurements(content_str)
+    ref_count = count_measurements(ref_content)
+
+    result.metrics["reference_measurement_count"] = ref_count
+
+    if gen_count != ref_count:
+        diff = ref_count - gen_count
+        if diff > 0:
+            result.add_error(
+                f"Missing {diff} measurements: generated {gen_count} vs reference {ref_count}"
+            )
+        else:
+            result.add_warning(
+                f"Extra {-diff} measurements: generated {gen_count} vs reference {ref_count}"
+            )
+
+    # Compare sample roles
+    gen_roles = set(re.findall(r'"sample.role.type":\s*"([^"]+)"', content_str))
+    ref_roles = set(re.findall(r'"sample role type":\s*"([^"]+)"', ref_content))
+
+    missing_roles = ref_roles - gen_roles
+    if missing_roles:
+        result.add_warning(f"Missing sample roles from reference: {missing_roles}")
+
+    # Compare nested document presence
+    ref_has_sample_doc = '"sample document"' in ref_content.lower()
+    gen_has_sample_doc = (
+        '"sample document"' in content_str.lower() or '"sample-document"' in content_str
+    )
+
+    if ref_has_sample_doc and not gen_has_sample_doc:
+        result.add_error(
+            "Reference has 'sample document' but generated ASM does not - fields may be incorrectly flattened"
+        )
+
+    ref_has_device_control = (
+        '"device control aggregate document"' in ref_content.lower()
+    )
+    gen_has_device_control = (
+        '"device control aggregate document"' in content_str.lower()
+        or '"device-control-aggregate-document"' in content_str
+    )
+
+    if ref_has_device_control and not gen_has_device_control:
+        result.add_error(
+            "Reference has 'device control aggregate document' but generated ASM does not"
+        )
+
+    ref_has_custom_info = '"custom information document"' in ref_content.lower()
+    gen_has_custom_info = (
+        '"custom information document"' in content_str.lower()
+        or '"custom-information-document"' in content_str
+    )
+
+    if ref_has_custom_info and not gen_has_custom_info:
+        result.add_warning(
+            "Reference has 'custom information document' for vendor fields but generated ASM does not"
+        )
+
+
+def validate_asm(
+    filepath: str, reference_path: Optional[str] = None, strict: bool = False
+) -> ValidationResult:
+    """
+    Validate ASM JSON file.
+
+    Args:
+        filepath: Path to ASM JSON file
+        reference_path: Optional path to reference ASM for comparison
+        strict: If True, treat warnings as errors
+
+    Returns:
+        ValidationResult with errors, warnings, and metrics
+    """
+    result = ValidationResult()
+
+    # Load ASM file
+    try:
+        with open(filepath, "r", encoding="utf-8") as f:
+            content_str = f.read()
+            asm = json.loads(content_str)
+    except json.JSONDecodeError as e:
+        result.add_error(f"Invalid JSON: {e}")
+        return result
+    except FileNotFoundError:
+        result.add_error(f"File not found: {filepath}")
+        return result
+
+    result.add_info(f"Validating: {filepath}")
+
+    # Run validations
+    validate_manifest(asm, result)
+    validate_technique(asm, result, content_str)
+    validate_naming_conventions(content_str, result)
+    validate_measurements(content_str, result)
+    validate_sample_roles(content_str, result)
+    validate_statistics(asm, content_str, result)
+    validate_units(content_str, result)
+    validate_metadata(content_str, result)
+    validate_calculated_data(content_str, result)
+    validate_unique_identifiers(content_str, result)
+
+    # NEW: Nested document structure validation
+    validate_nested_document_structure(asm, content_str, result)
+    validate_liquid_handler_structure(asm, content_str, result)
+
+    # Compare to reference if provided
+    if reference_path:
+        try:
+            with open(reference_path, "r", encoding="utf-8") as f:
+                ref_content = f.read()
+                reference = json.loads(ref_content)
+            compare_to_reference(asm, reference, content_str, ref_content, result)
+        except Exception as e:
+            result.add_warning(f"Could not load reference file: {e}")
+
+    # In strict mode, convert warnings to errors
+    if strict:
+        result.errors.extend([w.replace("WARNING", "ERROR") for w in result.warnings])
+        result.warnings = []
+
+    return result
+
+
+def main():
+    parser = argparse.ArgumentParser(description="Validate ASM JSON output")
+    parser.add_argument("input", help="ASM JSON file to validate")
+    parser.add_argument("--reference", "-r", help="Reference ASM file for comparison")
+    parser.add_argument(
+        "--strict", "-s", action="store_true", help="Treat warnings as errors"
+    )
+    parser.add_argument("--quiet", "-q", action="store_true", help="Only show errors")
+
+    args = parser.parse_args()
+
+    result = validate_asm(args.input, args.reference, args.strict)
+
+    if args.quiet:
+        if result.errors:
+            for error in result.errors:
+                print(error)
+            sys.exit(1)
+        sys.exit(0)
+
+    result.print_report()
+    sys.exit(0 if result.is_valid() else 1)
+
+
+if __name__ == "__main__":
+    main()