JuliaMSI/src/Precalculations.jl

using StatsBase # For mean, std, median, quantile, mad

# =============================================================================
# 7) Spatial & Advanced Processing (Stubs & New Functions)
# =============================================================================

"""
    find_ppm_error_by_region(msi_data::MSIData, region_masks::Dict, reference_peaks::Dict) -> Dict

Calculates and reports mass accuracy (PPM error) statistics for different spatial regions
defined by masks. This is useful for identifying spatial variations in calibration.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `region_masks::Dict{Symbol, BitMatrix}`: A dictionary mapping region names (e.g., `:tumor`, `:stroma`)
  to `BitMatrix` masks. The dimensions of each mask must match `msi_data.image_dims`.
- `reference_peaks::Dict{Float64, String}`: A dictionary of known reference peaks, mapping
  theoretical m/z to a name.

# Returns
- `Dict{Symbol, NamedTuple}`: A dictionary where keys are region names and values are `NamedTuple`s
  containing the mass accuracy report for that region, as generated by `analyze_mass_accuracy`.
"""
function find_ppm_error_by_region(msi_data::MSIData, region_masks::Dict, reference_peaks::Dict)
    regional_reports = Dict{Symbol, NamedTuple}()
    
    width, height = msi_data.image_dims
    
    for (region_name, mask) in region_masks
        mask_height, mask_width = size(mask)
        if mask_width != width || mask_height != height
            @warn "Mask dimensions ($(mask_width)x$(mask_height)) for region '$region_name' do not match image dimensions ($(width)x$(height)). Skipping."
            continue
        end

        indices = [
            i for i in 1:length(msi_data.spectra_metadata) 
            if msi_data.spectra_metadata[i].x > 0 &&
               msi_data.spectra_metadata[i].y > 0 &&
               mask[msi_data.spectra_metadata[i].y, msi_data.spectra_metadata[i].x]
        ]
        
        if isempty(indices) continue end
        
        # Call analyze_mass_accuracy with the specific indices for the region
        regional_reports[region_name] = analyze_mass_accuracy(msi_data, reference_peaks; spectrum_indices=indices)
    end
    return regional_reports
end

"""
    analyze_mass_accuracy(msi_data, reference_peaks; ...) -> NamedTuple

Analyzes the mass accuracy for a given subset of spectra by comparing detected peaks
against a list of known reference masses.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `reference_peaks::Dict{Float64, String}`: A dictionary of known reference peaks, mapping
  theoretical m/z to a name.
- `spectrum_indices::AbstractVector{Int}`: A vector of indices for the spectra to be analyzed.
- `peak_detection_snr_threshold::Float64`: The Signal-to-Noise ratio threshold to use for
  detecting peaks within the spectra.
- `ppm_tolerance_for_matching::Float64`: The tolerance in Parts Per Million (PPM) used to match
  a detected peak to a reference peak.

# Returns
- `NamedTuple`: A report containing summary statistics of the PPM errors found, including:
  - `mean_ppm_error`, `median_ppm_error`, `std_ppm_error`, `min_ppm_error`, `max_ppm_error`
  - `total_matched_peaks`: The total count of successful matches between detected and reference peaks.
  - `total_spectra_analyzed`: The number of spectra processed.
"""
function analyze_mass_accuracy(
    msi_data::MSIData,
    reference_peaks::Dict{Float64, String}; # m/z => name
    spectrum_indices::AbstractVector{Int},
    peak_detection_snr_threshold::Float64 = 2.0,
    ppm_tolerance_for_matching::Float64 = 50.0
    )::NamedTuple
    println("Analyzing mass accuracy for $(length(spectrum_indices)) spectra...")

    all_ppm_errors = Float64[]
    total_matched_peaks = 0
    total_spectra_processed = 0

    _iterate_spectra_fast(msi_data, spectrum_indices) do idx, mz, intensity
        total_spectra_processed += 1
        if !validate_spectrum(mz, intensity)
            @warn "Spectrum $idx is invalid, skipping mass accuracy analysis for it."
            return
        end

        detected_peaks = detect_peaks_profile_core(mz, intensity; snr_threshold=peak_detection_snr_threshold)

        for ref_mz in keys(reference_peaks)
            # Find the closest detected peak to this reference m/z within tolerance
            min_ppm_error = Inf
            best_matched_peak_mz = nothing

            for p in detected_peaks
                ppm_error = calculate_ppm_error(p.mz, ref_mz)
                if ppm_error <= ppm_tolerance_for_matching && ppm_error < min_ppm_error
                    min_ppm_error = ppm_error
                    best_matched_peak_mz = p.mz
                end
            end

            if best_matched_peak_mz !== nothing
                push!(all_ppm_errors, min_ppm_error)
                total_matched_peaks += 1
            end
        end
    end

    if isempty(all_ppm_errors)
        @warn "No reference peaks matched in any of the $(total_spectra_processed) processed spectra."
        return (
            mean_ppm_error = NaN,
            median_ppm_error = NaN,
            std_ppm_error = NaN,
            min_ppm_error = NaN,
            max_ppm_error = NaN,
            total_matched_peaks = 0,
            total_spectra_analyzed = total_spectra_processed,
            ppm_error_distribution = Float64[]
        )
    end

    # Calculate summary statistics
    mean_err = mean(all_ppm_errors)
    median_err = median(all_ppm_errors)
    std_err = std(all_ppm_errors)
    min_err = minimum(all_ppm_errors)
    max_err = maximum(all_ppm_errors)

    println("Mass accuracy analysis complete for $(total_spectra_processed) spectra.")
    return (
        mean_ppm_error = mean_err,
        median_ppm_error = median_err,
        std_ppm_error = std_err,
        min_ppm_error = min_err,
        max_ppm_error = max_err,
        total_matched_peaks = total_matched_peaks,
        total_spectra_analyzed = total_spectra_processed,
        ppm_error_distribution = all_ppm_errors
    )
end

# =============================================================================
# 8) Advanced Peak Quality & Adaptive Parameters
# =============================================================================

"""
    calculate_adaptive_bin_tolerance(ppm_error_distribution) -> Float64

Calculates an appropriate binning tolerance in PPM based on the observed mass accuracy
distribution. The strategy is to set the tolerance to capture the vast majority of
peaks from the same analyte, typically using `mean + 3 * standard_deviation`.

# Arguments
- `ppm_error_distribution::Vector{Float64}`: A vector of PPM error values from a mass
  accuracy analysis.

# Returns
- `Float64`: The suggested binning tolerance in PPM, capped between 10.0 and 100.0.
"""
function calculate_adaptive_bin_tolerance(ppm_error_distribution::Vector{Float64})
    if isempty(ppm_error_distribution)
        return 20.0 # Default if no data
    end
    
    # Filter out NaN and infinite values
    valid_errors = filter(x -> isfinite(x), ppm_error_distribution)
    
    if isempty(valid_errors)
        return 20.0 # Default if no valid data
    end
    
    # A robust strategy: mean + 3 * std deviation to capture ~99.7% of peaks
    mean_err = mean(valid_errors)
    std_err = std(valid_errors)
    
    # Ensure we don't get NaN
    if !isfinite(mean_err) || !isfinite(std_err)
        return 20.0
    end
    
    tolerance = mean_err + 3 * std_err
    
    # Cap at reasonable value and ensure finite
    return min(max(tolerance, 10.0), 100.0)
end

"""
    calculate_preprocessing_hints(data::MSIData; sample_indices)::Dict{Symbol, Any}

Analyzes a sample of spectra to determine initial "hints" for preprocessing parameters.
This function provides quick, data-driven defaults for noise level, SNR, and smoothing.

# Arguments
- `data::MSIData`: The main MSI data object.
- `sample_indices::AbstractVector{Int}`: The indices of spectra to sample for the analysis.

# Returns
- `Dict{Symbol, Any}`: A dictionary of hints, including:
  - `:estimated_noise`: The mean noise level estimated using Median Absolute Deviation (MAD).
  - `:suggested_snr`: A default SNR threshold (typically 3.0).
  - `:suggested_smoothing_window`: A suggested window size for smoothing, based on instrument resolution if available.
"""
function calculate_preprocessing_hints(data::MSIData; sample_indices::AbstractVector{Int})::Dict{Symbol, Any}
    println("Calculating preprocessing hints from a sample of $(length(sample_indices)) spectra...")
    
    num_spectra = length(data.spectra_metadata)
    if num_spectra == 0 || isempty(sample_indices)
        @warn "No spectra in dataset/sample to calculate hints from."
        return Dict{Symbol, Any}(
            :estimated_noise => 1.0,
            :suggested_snr => 3.0,
            :suggested_smoothing_window => 9
        )
    end

    # Initialize hints with defaults immediately
    hints = Dict{Symbol, Any}(
        :estimated_noise => 1.0, 
        :suggested_snr => 3.0,   
        :suggested_smoothing_window => 9 
    )

    all_noise_levels = Float64[]

    for idx in sample_indices
        try
            mz, intensity = GetSpectrum(data, idx)
            if !isempty(intensity)
                noise = mad(intensity, normalize=true)
                if isfinite(noise) && noise > 0
                    push!(all_noise_levels, noise)
                end
            end
        catch e
            @warn "Could not access spectrum #$idx to calculate hints: $e. Skipping."
        end
    end
    
    if !isempty(all_noise_levels)
        estimated_noise = mean(all_noise_levels)
        hints[:estimated_noise] = estimated_noise
        println("  - Estimated Noise Level: $(round(estimated_noise, digits=4))")
        println("  - Suggested SNR Threshold: 3.0")
    else
        @warn "Could not estimate noise from sample. Using default hints."
        # Defaults already set in `hints` initialization
    end
    
    # Suggest smoothing window based on resolution (if available)
    if data.instrument_metadata !== nothing && data.instrument_metadata.resolution !== nothing
        res = data.instrument_metadata.resolution
        # Update suggested smoothing window if resolution is known
        if res > 40000
            hints[:suggested_smoothing_window] = 5
        elseif res > 10000
            hints[:suggested_smoothing_window] = 7
        else
            hints[:suggested_smoothing_window] = 9
        end
    end
    println("  - Suggested Smoothing Window: $(hints[:suggested_smoothing_window])")

    println("Preprocessing hints calculated.")
    return hints
end

"""
    analyze_instrument_characteristics(msi_data::MSIData; sample_indices)::Dict

Analyzes instrument metadata and spectral data to infer key acquisition properties.
It combines information from the `msi_data.instrument_metadata` with direct analysis
of the spectra.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `sample_indices::AbstractVector{Int}`: The indices of spectra to sample for the analysis.

# Returns
- `Dict{Symbol, Any}`: A dictionary summarizing instrument characteristics:
  - `:acquisition_mode`: Inferred as `:profile`, `:centroid`, or `:mixed`.
  - `:mz_axis_type`: Inferred as `:regular` or `:irregular` based on m/z step consistency.
  - `:dynamic_range`: An estimate of the intensity dynamic range in orders of magnitude.
  - Other fields from `instrument_metadata` like `:resolution`, `:polarity`, etc.
"""
function analyze_instrument_characteristics(msi_data::MSIData; sample_indices::AbstractVector{Int})::Dict
    results = Dict{Symbol, Any}()
    
    # Use instrument metadata if available
    if msi_data.instrument_metadata !== nothing
        inst = msi_data.instrument_metadata
        results[:resolution] = inst.resolution
        results[:mass_accuracy_ppm] = inst.mass_accuracy_ppm
        results[:instrument_model] = inst.instrument_model
        results[:polarity] = inst.polarity
        results[:calibration_status] = inst.calibration_status
        results[:vendor_preprocessing] = inst.vendor_preprocessing_steps
    end
    
    # Analyze data characteristics from spectra
    println("  Analyzing data characteristics from spectra...")
    
    spectrum_modes = Set{SpectrumMode}()
    mz_step_sizes = Float64[]
    intensity_ranges = Tuple{Float64, Float64}[]  # (min, max) per spectrum
    
    if isempty(sample_indices)
        @warn "No indices to sample for instrument characteristics analysis."
        results[:acquisition_mode] = :unknown
        results[:mz_axis_type] = :unknown
        results[:dynamic_range] = 3.0
        return results
    end
    
    _iterate_spectra_fast(msi_data, sample_indices) do idx, mz, intensity
        # Record spectrum mode
        push!(spectrum_modes, msi_data.spectra_metadata[idx].mode)
        
        # Calculate m/z step statistics (for profile data)
        if length(mz) > 1 && msi_data.spectra_metadata[idx].mode == PROFILE
            steps = diff(mz)
            if !isempty(steps)
                push!(mz_step_sizes, mean(steps))
            end
        end
        
        # Record intensity range
        if !isempty(intensity)
            push!(intensity_ranges, (minimum(intensity), maximum(intensity)))
        end
    end
    
    # Determine acquisition mode
    if length(spectrum_modes) == 1
        results[:acquisition_mode] = first(spectrum_modes) == CENTROID ? :centroid : :profile
    else
        results[:acquisition_mode] = :mixed
    end
    
    # Determine m/z axis regularity
    if !isempty(mz_step_sizes)
        avg_step = mean(mz_step_sizes)
        step_std = std(mz_step_sizes)
        results[:mz_axis_type] = step_std / avg_step < 0.01 ? :regular : :irregular
        results[:average_mz_step] = avg_step
    else
        results[:mz_axis_type] = :unknown
    end
    
    # Enhanced dynamic range calculation
    if !isempty(intensity_ranges)
        println("DEBUG: Found $(length(intensity_ranges)) intensity ranges")
        
        # FIX: Handle cases where min intensities are zero
        max_intensities = Float64[]
        min_positive_intensities = Float64[]
        
        for (min_val, max_val) in intensity_ranges
            if max_val > 1e-6  # Valid maximum
                push!(max_intensities, max_val)
                
                # Find the smallest positive intensity in the spectrum
                # For now, use a reasonable estimate: 1% of the noise level
                # In practice, you'd want to sample the actual spectrum
                if max_val > 0
                    # Estimate minimum detectable signal as ~3x noise level
                    estimated_min_signal = max_val * 1e-4  # Conservative estimate
                    push!(min_positive_intensities, estimated_min_signal)
                end
            end
        end
        
        println("DEBUG: Valid max intensities: $(length(max_intensities)), estimated min intensities: $(length(min_positive_intensities))")
        
        if !isempty(max_intensities) && !isempty(min_positive_intensities)
            avg_max = mean(max_intensities)
            avg_min = mean(min_positive_intensities)
            if avg_min > 0
                dynamic_range = log10(avg_max / avg_min)
                results[:dynamic_range] = dynamic_range
                println("DEBUG: Dynamic range calculated: $dynamic_range (avg_max=$avg_max, avg_min=$avg_min)")
            else
                results[:dynamic_range] = 0.0
            end
        else
            # Estimate based on typical values
            results[:dynamic_range] = 3.0  # Typical for MS data
        end
    else
        results[:dynamic_range] = 3.0  # Default estimate
    end
    
    println("  - Acquisition mode: $(results[:acquisition_mode])")
    println("  - m/z axis type: $(results[:mz_axis_type])")
    println("  - Dynamic range: $(round(get(results, :dynamic_range, 0), digits=2))")
    
    return results
end

"""
    analyze_signal_quality(msi_data::MSIData; sample_indices)::Dict

Analyzes a sample of spectra to assess signal quality, including noise levels,
Signal-to-Noise Ratio (SNR), and Total Ion Current (TIC) variation.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `sample_indices::AbstractVector{Int}`: The indices of spectra to sample for the analysis.

# Returns
- `Dict{Symbol, Any}`: A dictionary of signal quality metrics:
  - `:noise_mean`, `:noise_std`, `:noise_cv`: Statistics of the noise level.
  - `:snr_mean`, `:snr_median`, `:snr_95th`: Distribution statistics of the estimated SNR.
  - `:tic_mean`, `:tic_std`, `:tic_cv`: Statistics of the Total Ion Current.
"""
function analyze_signal_quality(msi_data::MSIData; sample_indices::AbstractVector{Int})::Dict
    results = Dict{Symbol, Any}()
    
    println("  Analyzing signal quality from $(length(sample_indices)) sample spectra...")
    
    # Use the existing function for basic noise estimation
    hints_from_calc = calculate_preprocessing_hints(msi_data, sample_indices=sample_indices)
    
    # Copy relevant hints to results, or handle cases where they might be missing
    results[:estimated_noise] = get(hints_from_calc, :estimated_noise, 1.0)
    results[:suggested_snr] = get(hints_from_calc, :suggested_snr, 3.0)
    results[:suggested_smoothing_window] = get(hints_from_calc, :suggested_smoothing_window, 9)
    
    # Enhanced noise analysis
    noise_levels = Float64[]
    snr_distribution = Float64[]
    tic_values = Float64[]
    
    if isempty(sample_indices)
        @warn "No indices to sample for signal quality analysis."
        return results
    end
    
    _iterate_spectra_fast(msi_data, sample_indices) do idx, mz, intensity
        if !isempty(intensity)
            # Noise estimation using MAD
            noise = mad(intensity, normalize=true)
            push!(noise_levels, noise)
            
            # FIX: More robust SNR calculation
            valid_intensity = intensity[intensity .> 0]  # Remove zeros
            if !isempty(valid_intensity)
                # Use robust signal estimate (95th percentile instead of max)
                signal_estimate = quantile(valid_intensity, 0.95)
                noise_robust = max(noise, 1e-6)  # Avoid division by zero
                
                if noise_robust > 0 && isfinite(signal_estimate)
                    snr_val = signal_estimate / noise_robust
                    # Cap unrealistic SNR values
                    push!(snr_distribution, min(snr_val, 1e6))
                end
            end
            
            # Total ion count
            push!(tic_values, sum(intensity))
        end
    end
    
    if !isempty(noise_levels)
        results[:noise_mean] = mean(noise_levels)
        results[:noise_std] = std(noise_levels)
        results[:noise_cv] = results[:noise_std] / results[:noise_mean]  # Coefficient of variation
    end
    
    if !isempty(snr_distribution)
        results[:snr_mean] = mean(snr_distribution)
        results[:snr_median] = median(snr_distribution)
        results[:snr_95th] = quantile(snr_distribution, 0.95)
    end
    
    if !isempty(tic_values)
        results[:tic_mean] = mean(tic_values)
        results[:tic_std] = std(tic_values)
        results[:tic_cv] = results[:tic_std] / results[:tic_mean]
    end
    
    println("  - Estimated noise level: $(round(get(results, :noise_mean, 0), digits=4))")
    println("  - Average SNR: $(round(get(results, :snr_mean, 0), digits=2))")
    println("  - TIC CV: $(round(get(results, :tic_cv, 0) * 100, digits=1))%")
    
    return results
end

"""
    analyze_mass_accuracy_global(msi_data, reference_peaks; spectrum_indices)::Dict

Performs a global mass accuracy analysis across a sample of spectra and suggests an
adaptive binning tolerance.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `reference_peaks::Dict`: A dictionary of known reference peaks.
- `spectrum_indices::AbstractVector{Int}`: The indices of spectra to sample for the analysis.

# Returns
- `Dict{Symbol, Any}`: A dictionary containing:
  - `:global_accuracy`: The `NamedTuple` report from `analyze_mass_accuracy`.
  - `:suggested_bin_tolerance`: An adaptive tolerance in PPM for peak binning, derived
    from the mass accuracy results.
"""
function analyze_mass_accuracy_global(msi_data::MSIData, reference_peaks::Dict; 
                                       spectrum_indices::AbstractVector{Int})::Dict
    results = Dict{Symbol, Any}()
    
    println("  Analyzing mass accuracy using $(length(reference_peaks)) reference peaks on $(length(spectrum_indices)) spectra...")
    
    if isempty(spectrum_indices)
        @warn "No indices to sample for mass accuracy analysis."
        # Return a structure indicating no analysis was performed
        empty_report = (
            mean_ppm_error = NaN, median_ppm_error = NaN, std_ppm_error = NaN,
            min_ppm_error = NaN, max_ppm_error = NaN, total_matched_peaks = 0,
            total_spectra_analyzed = 0, ppm_error_distribution = Float64[]
        )
        results[:global_accuracy] = empty_report
        results[:suggested_bin_tolerance] = 20.0 # Default
        return results
    end
    
    # Use the existing analyze_mass_accuracy function with the provided indices
    accuracy_report = analyze_mass_accuracy(msi_data, reference_peaks; 
                                          spectrum_indices=spectrum_indices)
    
    results[:global_accuracy] = accuracy_report
    results[:suggested_bin_tolerance] = calculate_adaptive_bin_tolerance(
        accuracy_report.ppm_error_distribution
    )
    
    println("  - Mean PPM error: $(round(accuracy_report.mean_ppm_error, digits=2))")
    println("  - Suggested bin tolerance: $(round(results[:suggested_bin_tolerance], digits=2)) ppm")
    
    return results
end

"""
    analyze_spatial_regions(msi_data, region_masks, reference_peaks)::Dict

Analyzes different spatial regions for variations in mass accuracy. This function is a
wrapper around `find_ppm_error_by_region` and summarizes the results.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `region_masks::Dict`: A dictionary of named `BitMatrix` masks for each region.
- `reference_peaks::Dict`: A dictionary of known reference peaks.

# Returns
- `Dict{Symbol, Any}`: A dictionary containing:
  - `:regional_ppm_errors`: A dictionary mapping each region name to its mass accuracy report.
  - `:max_regional_ppm_difference`: The difference between the highest and lowest mean PPM
    error across all analyzed regions.
"""
function analyze_spatial_regions(msi_data::MSIData, region_masks::Dict, reference_peaks::Dict)::Dict
    results = Dict{Symbol, Any}()
    
    println("  Analyzing $(length(region_masks)) spatial regions...")
    
    # Use the existing function
    regional_reports = find_ppm_error_by_region(msi_data, region_masks, reference_peaks)
    
    results[:regional_ppm_errors] = regional_reports
    
    # Calculate regional variations
    if !isempty(regional_reports)
        mean_errors = [report.mean_ppm_error for report in values(regional_reports) if isfinite(report.mean_ppm_error)]
        if !isempty(mean_errors)
            results[:max_regional_ppm_difference] = maximum(mean_errors) - minimum(mean_errors)
        end
    end
    
    for (region, report) in regional_reports
        println("  - $region: $(round(report.mean_ppm_error, digits=2)) ppm (n=$(report.total_spectra_analyzed))")
    end
    
    return results
end

"""
    analyze_peak_characteristics(msi_data, instrument_analysis, mass_accuracy_results; spectrum_indices)::Dict

Analyzes peak shape, width, and quality from a sample of spectra. The behavior
adapts based on whether the data is in `:profile` or `:centroid` mode.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `instrument_analysis::Dict`: The output from `analyze_instrument_characteristics`.
- `mass_accuracy_results`: The output from `analyze_mass_accuracy_global`.
- `spectrum_indices::AbstractVector{Int}`: The indices of spectra to sample.

# Returns
- `Dict{Symbol, Any}`: A dictionary of peak metrics:
  - `:mean_fwhm_ppm`, `:median_fwhm_ppm`: Statistics of Full Width at Half Maximum (FWHM).
    For centroid data, this is estimated from mass accuracy.
  - `:mean_gaussian_r2`: The average goodness-of-fit to a Gaussian shape (profile data only).
  - `:peak_resolution_estimate`: An estimate of instrument resolution based on FWHM.
  - `:mean_peaks_per_spectrum`: The average number of peaks detected per spectrum.
"""
function analyze_peak_characteristics(msi_data::MSIData, instrument_analysis::Dict, mass_accuracy_results; 
                                    spectrum_indices::AbstractVector{Int})::Dict
    results = Dict{Symbol, Any}()
    
    # Determine acquisition mode from the analysis results, not from metadata
    acquisition_mode = get(instrument_analysis, :acquisition_mode, :unknown)
    
    # Calculate estimated_mean_ppm_error for fallback logic
    estimated_mean_ppm_error = 30.0 # Default if mass_accuracy_results is nothing or invalid
    if mass_accuracy_results !== nothing && haskey(mass_accuracy_results, :global_accuracy) && isa(mass_accuracy_results[:global_accuracy], NamedTuple)
        ppm_error_report = mass_accuracy_results[:global_accuracy]
        mean_ppm_error_val = get(ppm_error_report, :mean_ppm_error, 30.0)
        if isfinite(mean_ppm_error_val)
            estimated_mean_ppm_error = mean_ppm_error_val
        end
    end

    if isempty(spectrum_indices)
        @warn "No indices to sample for peak characteristics analysis."
        # Provide sensible defaults if no analysis can be run
        if acquisition_mode == :centroid
            # Much more permissive defaults for centroid data
            results[:mean_fwhm_ppm] = 50.0
            results[:median_fwhm_ppm] = 50.0
            results[:mean_gaussian_r2] = 0.0  # Disable shape filtering for centroids
            results[:peak_resolution_estimate] = 20000.0
            results[:mean_peaks_per_spectrum] = 1000
        else
            estimated_fwhm = estimated_mean_ppm_error * (acquisition_mode == :profile ? 3 : 2)
            results[:mean_fwhm_ppm] = estimated_fwhm
            results[:median_fwhm_ppm] = estimated_fwhm
            results[:mean_gaussian_r2] = acquisition_mode == :profile ? 0.7 : 0.9
            results[:peak_resolution_estimate] = 1e6 / estimated_fwhm
            results[:mean_peaks_per_spectrum] = 0
        end
        return results
    end

    if acquisition_mode == PROFILE
        println("  Analyzing peak characteristics for PROFILE mode from $(length(spectrum_indices)) sample spectra...")
        
        peak_widths_ppm = Float64[]
        r_squared_values = Float64[]
        peak_counts = Int[]
        fwhm_values = Float64[]
        
        spectra_analyzed = 0
        peaks_analyzed = 0
        
        _iterate_spectra_fast(msi_data, spectrum_indices) do idx, mz, intensity
            if length(mz) < 10  # Skip spectra with too few points
                return
            end
            
            spectra_analyzed += 1
            meta = msi_data.spectra_metadata[idx]
            
            # Detect peaks with lower SNR threshold to find more peaks
            peaks = detect_peaks_profile_core(mz, intensity; snr_threshold=2.0)
            push!(peak_counts, length(peaks))
            
            if !isempty(peaks)
                # Analyze the strongest 3 peaks per spectrum
                sorted_peaks = sort(peaks, by=p->p.intensity, rev=true)
                for peak in sorted_peaks[1:min(3, length(sorted_peaks))]
                    try
                        # Find the index of the peak in the original mz array
                        peak_idx = argmin(abs.(mz .- peak.mz))
                        
                        fwhm_delta_m = calculate_robust_fwhm(mz, intensity, peak_idx)
                        
                        if !isnan(fwhm_delta_m) && fwhm_delta_m > 0.001 && fwhm_delta_m < 0.5  # Reasonable range in Da
                            fwhm_ppm = 1e6 * fwhm_delta_m / peak.mz
                            if 5.0 < fwhm_ppm < 500.0  # Reasonable ppm range
                                push!(peak_widths_ppm, fwhm_ppm)
                                push!(fwhm_values, fwhm_delta_m)
                                
                                r2 = _fit_gaussian_and_r2(mz, intensity, peak_idx, 5)
                                push!(r_squared_values, r2)
                                peaks_analyzed += 1
                                
                                if peaks_analyzed <= 3
                                    println("DEBUG: Peak at m/z $(peak.mz), FWHM = $(fwhm_ppm) ppm, R² = $r2")
                                end
                            end
                        end
                    catch e
                        continue
                    end
                end
            end
        end
        
        println("DEBUG: Analyzed $peaks_analyzed peaks from $spectra_analyzed spectra")
        
        if !isempty(peak_widths_ppm)
            results[:mean_fwhm_ppm] = mean(peak_widths_ppm)
            results[:median_fwhm_ppm] = median(peak_widths_ppm)
            results[:mean_gaussian_r2] = mean(r_squared_values)
            results[:peak_resolution_estimate] = 1e6 / results[:mean_fwhm_ppm]
            println("  - Actual FWHM measurement: $(round(results[:mean_fwhm_ppm], digits=2)) ppm")
        else
            # Fallback if no valid peaks found in PROFILE mode
            estimated_fwhm = estimated_mean_ppm_error * 3  # FWHM typically wider than mass error
            results[:mean_fwhm_ppm] = estimated_fwhm
            results[:median_fwhm_ppm] = estimated_fwhm
            results[:mean_gaussian_r2] = 0.7
            results[:peak_resolution_estimate] = 1e6 / estimated_fwhm
            println("  - Estimated FWHM (from mass accuracy): $estimated_fwhm ppm")
        end
        
        if !isempty(peak_counts)
            results[:mean_peaks_per_spectrum] = mean(peak_counts)
        else
            results[:mean_peaks_per_spectrum] = 0
        end
    
    else # CENTROID mode
        println("  Analyzing peak characteristics for CENTROID mode from $(length(spectrum_indices)) sample spectra...")
        
        peak_counts = Int[]
        
        _iterate_spectra_fast(msi_data, spectrum_indices) do idx, mz, intensity
            if !isempty(mz)
                push!(peak_counts, length(mz))
            end
        end
        
        if !isempty(peak_counts)
            results[:mean_peaks_per_spectrum] = mean(peak_counts)
            results[:median_peaks_per_spectrum] = median(peak_counts)
            results[:total_peaks_detected] = sum(peak_counts)
        else
            results[:mean_peaks_per_spectrum] = 0
            results[:median_peaks_per_spectrum] = 0
            results[:total_peaks_detected] = 0
        end
        
        # For centroid data, use much more permissive parameters
        # Don't estimate FWHM from mass accuracy - use reasonable defaults
        results[:mean_fwhm_ppm] = 50.0  # Reasonable default for centroid data
        results[:median_fwhm_ppm] = 50.0
        results[:mean_gaussian_r2] = 0.0  # Disable shape filtering for centroids
        results[:peak_resolution_estimate] = 20000.0  # Reasonable estimate
        
        println("  - Mean peaks per spectrum: $(round(results[:mean_peaks_per_spectrum], digits=1))")
        println("  - Using permissive FWHM for centroid data: 50.0 ppm")
        println("  - Shape filtering disabled for centroid data")
    end
    
    # Common prints
    println("  - Mean Gaussian R²: $(round(get(results, :mean_gaussian_r2, 0.0), digits=3))")
    println("  - Mean peaks per spectrum: $(round(get(results, :mean_peaks_per_spectrum, 0.0), digits=1))")
    
    return results
end

"""
    generate_preprocessing_recommendations(analysis_results::Dict)::Dict{Symbol, Any}

Generates intelligent preprocessing recommendations by synthesizing the results from
various analysis functions (`analyze_instrument_characteristics`, `analyze_signal_quality`, etc.).

# Arguments
- `analysis_results::Dict`: A dictionary containing the comprehensive analysis results from
  the `run_preprocessing_analysis` pipeline.

# Returns
- `Dict{Symbol, Any}`: A dictionary where keys are preprocessing step names (e.g., `:smoothing`,
  `:peak_picking`) and values are dictionaries of recommended parameters for that step.
"""
function generate_preprocessing_recommendations(analysis_results::Dict)::Dict{Symbol, Any}
    recommendations = Dict{Symbol, Any}()
    
    inst_analysis = get(analysis_results, :instrument_analysis, Dict())
    signal_analysis = get(analysis_results, :signal_analysis, Dict())
    mass_accuracy = get(analysis_results, :mass_accuracy, Dict())
    peak_analysis = get(analysis_results, :peak_analysis, Dict())
    
    # Stabilization Recommendations
    recommendations[:stabilization] = generate_stabilization_recommendations(signal_analysis)

    # Baseline Correction Recommendations
    recommendations[:baseline_correction] = generate_baseline_recommendations(inst_analysis, signal_analysis)
    
    # Smoothing Recommendations
    recommendations[:smoothing] = generate_smoothing_recommendations(inst_analysis, peak_analysis)
    
    # Peak Picking Recommendations - pass instrument analysis
    recommendations[:peak_picking] = generate_peak_picking_recommendations(signal_analysis, peak_analysis, inst_analysis)
    
    # Normalization Recommendations
    recommendations[:normalization] = generate_normalization_recommendations(signal_analysis)
    
    # Alignment Recommendations
    recommendations[:alignment] = generate_alignment_recommendations(mass_accuracy, inst_analysis)
    
    # Binning Recommendations
    recommendations[:binning] = generate_binning_recommendations(peak_analysis, mass_accuracy)
    
    return recommendations
end

"""Generate baseline correction recommendations based on data properties."""
function generate_baseline_recommendations(inst_analysis, signal_analysis)
    recommendations = Dict{Symbol, Any}()
    
    # Determine baseline correction method based on data characteristics
    acquisition_mode = get(inst_analysis, :acquisition_mode, :unknown)
    noise_level = get(signal_analysis, :noise_mean, 1.0)
    
    if acquisition_mode == :profile
        recommendations[:method] = "SNIP"
        recommendations[:window_size] = 200  # Default, can be optimized
        recommendations[:iterations] = 100
    else
        recommendations[:method] = "linear"
        recommendations[:noise_threshold] = noise_level * 3
    end
    
    return recommendations
end

"""Generate smoothing recommendations based on peak width and m/z step."""
function generate_smoothing_recommendations(inst_analysis, peak_analysis)
    recommendations = Dict{Symbol, Any}()
    
    mz_step = get(inst_analysis, :average_mz_step, 0.01)
    fwhm_ppm = get(peak_analysis, :mean_fwhm_ppm, 20.0)
    
    # Convert FWHM from ppm to m/z units for typical m/z
    typical_mz = 500.0
    fwhm_mz = typical_mz * fwhm_ppm / 1e6
    
    # Savitzky-Golay window should be ~FWHM in points
    window_points = max(5, min(21, round(Int, fwhm_mz / mz_step)))
    # Ensure odd number
    window_points = isodd(window_points) ? window_points : window_points + 1
    
    recommendations[:method] = "Savitzky-Golay"
    recommendations[:window_size] = window_points
    recommendations[:polynomial_order] = 3
    
    return recommendations
end

"""Generate peak picking recommendations from signal and peak analyses."""
function generate_peak_picking_recommendations(signal_analysis, peak_analysis, inst_analysis)
    recommendations = Dict{Symbol, Any}()
    
    acquisition_mode = get(inst_analysis, :acquisition_mode, :profile)
    
    if acquisition_mode == :centroid
        # Much more permissive parameters for centroid data
        recommendations[:snr_threshold] = 2.0  # Lower threshold for centroid
        recommendations[:min_peak_width_ppm] = 0.0   # No minimum width for centroids
        recommendations[:max_peak_width_ppm] = 200.0 # Very wide maximum for centroids
        recommendations[:reason] = "Centroid data: using permissive parameters"
    else
        # Existing profile mode logic
        snr_threshold = get(signal_analysis, :suggested_snr, 3.0)
        fwhm_ppm = get(peak_analysis, :mean_fwhm_ppm, 20.0)
        
        recommendations[:snr_threshold] = snr_threshold
        recommendations[:min_peak_width_ppm] = fwhm_ppm * 0.5
        recommendations[:max_peak_width_ppm] = fwhm_ppm * 3.0
        recommendations[:reason] = "Profile data: using standard parameters"
    end
    
    return recommendations
end

"""Generate normalization recommendations based on TIC variation."""
function generate_normalization_recommendations(signal_analysis)
    recommendations = Dict{Symbol, Any}()
    
    tic_cv = get(signal_analysis, :tic_cv, 0.5)
    
    if tic_cv < 0.3  # Low TIC variation
        recommendations[:method] = "TIC"
        recommendations[:reason] = "Low TIC variation across spectra"
    else  # High TIC variation
        recommendations[:method] = "RMS"
        recommendations[:reason] = "High TIC variation, using robust normalization"
    end
    
    return recommendations
end

"""Generate alignment recommendations based on calibration status and mass error."""
function generate_alignment_recommendations(mass_accuracy, inst_analysis)
    recommendations = Dict{Symbol, Any}()
    
    calibration_status = get(inst_analysis, :calibration_status, :uncalibrated)

    mean_ppm_error_val = 10.0 # Default value
    if mass_accuracy !== nothing && haskey(mass_accuracy, :global_accuracy) && isa(mass_accuracy[:global_accuracy], NamedTuple)
        ppm_error_report = mass_accuracy[:global_accuracy]
        mean_ppm_error_val = get(ppm_error_report, :mean_ppm_error, 10.0)
    end
    
    if calibration_status == :uncalibrated || mean_ppm_error_val > 20.0
        recommendations[:method] = "reference_based"
        recommendations[:max_ppm_shift] = 50.0
        recommendations[:required] = true
    else
        recommendations[:method] = "none"
        recommendations[:required] = false
    end
    
    return recommendations
end

"""Generate binning recommendations based on peak width and mass accuracy."""
function generate_binning_recommendations(peak_analysis, mass_accuracy)
    recommendations = Dict{Symbol, Any}()
    
    fwhm_ppm = get(peak_analysis, :mean_fwhm_ppm, 20.0)
    
    # Handle the case when mass_accuracy is nothing or has NaN values
    suggested_tolerance = 20.0  # Default value
    if mass_accuracy !== nothing
        tol = get(mass_accuracy, :suggested_bin_tolerance, 20.0)
        if !isnan(tol) && isfinite(tol)
            suggested_tolerance = tol
        end
    end
    
    # Ensure fwhm_ppm is valid
    if isnan(fwhm_ppm) || !isfinite(fwhm_ppm)
        fwhm_ppm = 20.0
    end
    
    # Bin width should be ~FWHM/2 to preserve resolution while reducing data size
    bin_width_ppm = max(fwhm_ppm * 0.5, suggested_tolerance)
    
    recommendations[:method] = "adaptive"
    recommendations[:bin_width_ppm] = bin_width_ppm
    recommendations[:min_peaks_per_bin] = 3
    
    return recommendations
end

"""Generate intensity stabilization recommendations."""
function generate_stabilization_recommendations(signal_analysis)
    recommendations = Dict{Symbol, Any}()
    # Default to sqrt, as it's a common and generally robust transformation.
    # More advanced logic could analyze intensity distribution skewness if needed.
    recommendations[:method] = :sqrt 
    return recommendations
end

# =============================================================================
# Pre-Analysis Pipeline for Auto Parameter Determination
# =============================================================================

"""
    run_preprocessing_analysis(msi_data; ...)

Runs a comprehensive pre-analysis pipeline to determine optimal preprocessing parameters.
This function orchestrates a series of analysis steps on a sample of the dataset to
provide intelligent defaults for a full preprocessing workflow.

The pipeline consists of several phases:
1.  **Instrument & Data Characteristics**: Infers acquisition mode, m/z axis type, etc.
2.  **Noise & Signal Quality**: Estimates noise, SNR, and TIC variation.
3.  **Mass Accuracy**: Calculates PPM error against reference peaks (if provided).
4.  **Spatial Regions**: Analyzes regional variations (if masks are provided).
5.  **Peak Characteristics**: Measures peak width, shape, and density.
6.  **Recommendations**: Synthesizes all analysis results into actionable parameter suggestions.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `reference_peaks::Dict`: Optional. Known m/z values for mass accuracy analysis.
- `region_masks::Dict`: Optional. Named `BitMatrix` masks for regional analysis.
- `sample_size::Int`: The number of spectra to sample for the analysis.
- `mask_path::String`: Optional path to a PNG mask to restrict analysis to a specific ROI.
- `spectrum_indices::AbstractVector{Int}`: Optional vector of indices to restrict analysis to,
  overriding `mask_path` and `sample_size` for selection.

# Returns
- `Dict{Symbol, Any}`: A nested dictionary containing the results of each analysis phase
  and a final `:recommendations` dictionary. The recommendations are also stored in
  `msi_data.preprocessing_hints`.
"""
function run_preprocessing_analysis(msi_data::MSIData; 
                                   reference_peaks::Dict{Float64, String}=Dict{Float64, String}(),
                                   region_masks::Dict{Symbol, BitMatrix}=Dict{Symbol, BitMatrix}(),
                                   sample_size::Int=100,
                                   mask_path::Union{String, Nothing}=nothing,
                                   spectrum_indices::Union{AbstractVector{Int}, Nothing}=nothing)::Dict{Symbol, Any}
    
    println("="^60)
    println("RUNNING PRE-ANALYSIS PIPELINE")
    println("="^60)
    
    analysis_results = Dict{Symbol, Any}()

    local all_available_indices::AbstractVector{Int}

    if spectrum_indices !== nothing
        println("Using provided list of $(length(spectrum_indices)) spectrum indices.")
        all_available_indices = spectrum_indices
    elseif mask_path !== nothing
        println("Applying mask from: $(mask_path)")
        try
            mask_matrix = load_and_prepare_mask(mask_path, msi_data.image_dims)
            masked_indices_set = get_masked_spectrum_indices(msi_data, mask_matrix)
            all_available_indices = collect(masked_indices_set)
            println("Mask applied. $(length(all_available_indices)) spectra are within the masked region.")
        catch e
            @error "Failed to load or apply mask: $e. Proceeding without mask."
            all_available_indices = 1:length(msi_data.spectra_metadata)
        end
    else
        all_available_indices = 1:length(msi_data.spectra_metadata)
    end

    if isempty(all_available_indices)
        @warn "No spectra available for analysis (after applying mask/filter). Returning empty results."
        return analysis_results
    end

    # Create a single sample set from the available indices
    num_available = length(all_available_indices)
    indices_to_sample = if num_available > sample_size
        # Use StatsBase.sample for sampling without replacement
        sample(all_available_indices, sample_size, replace=false)
    else
        # Use all available indices if they are fewer than the sample size
        collect(all_available_indices)
    end
    
    # Ensure analytics are precomputed
    if !is_set(msi_data.analytics_ready)
        println("Pre-computing basic analytics...")
        precompute_analytics(msi_data)
    end
    
    # Phase 1: Instrument and Data Characteristics
    println("\n--- Phase 1: Instrument & Data Characteristics ---")
    instrument_analysis = analyze_instrument_characteristics(msi_data, sample_indices=indices_to_sample)
    analysis_results[:instrument_analysis] = instrument_analysis
    
    # Phase 2: Noise and Signal Quality Analysis
    println("\n--- Phase 2: Noise & Signal Quality Analysis ---")
    signal_analysis = analyze_signal_quality(msi_data, sample_indices=indices_to_sample)
    analysis_results[:signal_analysis] = signal_analysis
    
    # Phase 3: Mass Accuracy Analysis
    println("\n--- Phase 3: Mass Accuracy Analysis ---")
    if !isempty(reference_peaks)
        mass_accuracy_analysis = analyze_mass_accuracy_global(msi_data, reference_peaks, spectrum_indices=indices_to_sample)
        analysis_results[:mass_accuracy] = mass_accuracy_analysis
    else
        println("No reference peaks provided - skipping mass accuracy analysis")
        analysis_results[:mass_accuracy] = nothing
    end
    
    # Phase 4: Spatial Region Analysis (if masks provided)
    # This function is not affected by the global mask, as it analyzes specific, named regions.
    println("\n--- Phase 4: Spatial Region Analysis ---")
    if !isempty(region_masks)
        regional_analysis = analyze_spatial_regions(msi_data, region_masks, reference_peaks)
        analysis_results[:regional_analysis] = regional_analysis
    else
        println("No region masks provided - skipping regional analysis")
        analysis_results[:regional_analysis] = nothing
    end
    
    # Phase 5: Peak Characteristics Analysis
    println("\n--- Phase 5: Peak Characteristics Analysis ---")
    peak_analysis = analyze_peak_characteristics(msi_data, instrument_analysis, analysis_results[:mass_accuracy], spectrum_indices=indices_to_sample)
    analysis_results[:peak_analysis] = peak_analysis
    
    # Phase 6: Generate Preprocessing Recommendations
    println("\n--- Phase 6: Generating Preprocessing Recommendations ---")
    recommendations = generate_preprocessing_recommendations(analysis_results)
    analysis_results[:recommendations] = recommendations
    
    # Store in MSIData object
    msi_data.preprocessing_hints = recommendations
    
    println("\n" * "="^60)
    println("PRE-ANALYSIS COMPLETE")
    println("="^60)
    
    return analysis_results
end

"""
    calculate_ppm_error(measured_mz::Real, theoretical_mz::Real) -> Float64

Calculates the mass accuracy error in parts-per-million (PPM) between a measured
and a theoretical m/z value.

# Arguments
- `measured_mz::Real`: The experimentally measured m/z value.
- `theoretical_mz::Real`: The known, theoretical m/z value of a compound.

# Returns
- `Float64`: The calculated PPM error. Returns `Inf` if `theoretical_mz` is zero.

# Formula
`PPM = 10^6 * |measured_mz - theoretical_mz| / theoretical_mz`

# Example
```julia
calculate_ppm_error(100.005, 100.0) # returns 50.0
```
"""
function calculate_ppm_error(measured_mz::Real, theoretical_mz::Real)
    if theoretical_mz == 0
        return Inf
    end
    return 1e6 * abs(Float64(measured_mz) - Float64(theoretical_mz)) / Float64(theoretical_mz)
end

"""
    calculate_ppm_error_bulk(measured_mz::Vector{<:Real}, theoretical_mz::Vector{<:Real}) -> Vector{Float64}

Calculates PPM errors for multiple pairs of measured and theoretical mass values.

# Arguments
- `measured_mz::Vector{<:Real}`: A vector of experimentally measured m/z values.
- `theoretical_mz::Vector{<:Real}`: A vector of known, theoretical m/z values.

# Returns
- `Vector{Float64}`: A vector containing the calculated PPM error for each pair.
"""
function calculate_ppm_error_bulk(measured_mz::Vector{Real}, theoretical_mz::Vector{Real})
    return [calculate_ppm_error(m, t) for (m, t) in zip(measured_mz, theoretical_mz)]
end

"""
    calculate_resolution_fwhm(mz::Real, profile_mz::AbstractVector{<:Real}, profile_intensity::AbstractVector{<:Real}) -> Float64

Calculates the mass resolution of a peak in profile-mode data using the Full Width at
Half Maximum (FWHM) method. Resolution is a measure of an instrument's ability to
distinguish between two peaks of slightly different mass-to-charge ratios.

# Arguments
- `mz::Real`: The m/z value of the peak's centroid.
- `profile_mz::AbstractVector{<:Real}`: The full m/z array from the profile-mode spectrum.
- `profile_intensity::AbstractVector{<:Real}`: The full intensity array from the profile-mode spectrum.

# Returns
- `Float64`: The calculated resolution (`m / Δm`). Returns `NaN` if the FWHM cannot be determined (e.g., peak is at the edge of the spectrum).

# Formula
`Resolution = m / Δm`, where `Δm` is the FWHM.
"""
function calculate_resolution_fwhm(mz::Real, profile_mz::AbstractVector{<:Real},
                                 profile_intensity::AbstractVector{<:Real})
    
    # Find peak center index
    peak_idx = argmin(abs.(profile_mz .- mz))
    peak_height = Float64(profile_intensity[peak_idx])
    half_max = peak_height / 2
    
    # Find left half-maximum point (interpolate for accuracy)
    left_idx = find_last_below(profile_intensity[1:peak_idx], half_max)
    if left_idx == 0 || left_idx == length(profile_intensity[1:peak_idx])
        return NaN
    end
    
    # Linear interpolation for left FWHM
    x1, x2 = Float64(profile_mz[left_idx]), Float64(profile_mz[left_idx+1])
    y1, y2 = Float64(profile_intensity[left_idx]), Float64(profile_intensity[left_idx+1])
    denominator = y2 - y1
    if denominator == 0
        left_fwhm = NaN
    else
        left_fwhm = x1 + (x2 - x1) * (half_max - y1) / denominator
    end
    
    # Find right half-maximum point
    right_slice = profile_intensity[peak_idx:end]
    right_offset = find_first_below(right_slice, half_max)
    if right_offset == 0 || right_offset == length(right_slice)
        return NaN
    end
    
    right_idx = peak_idx + right_offset - 1
    x1, x2 = Float64(profile_mz[right_idx-1]), Float64(profile_mz[right_idx])
    y1, y2 = Float64(profile_intensity[right_idx-1]), Float64(profile_intensity[right_idx])
    denominator = y2 - y1
    if denominator == 0
        right_fwhm = NaN
    else
        right_fwhm = x1 + (x2 - x1) * (half_max - y1) / denominator
    end
    
    fwhm = right_fwhm - left_fwhm
    return fwhm > 0 ? Float64(mz) / fwhm : NaN
end

"""Helper to find the last index in a vector with a value below a threshold, used for FWHM."""
function find_last_below(v::AbstractVector{<:Real}, threshold::Real)
    for i in length(v):-1:2
        if v[i] >= threshold && v[i-1] < threshold
            return i-1
        end
    end
    return 0
end

"""Helper to find the first index in a vector with a value below a threshold, used for FWHM."""
function find_first_below(v::AbstractVector{<:Real}, threshold::Real)
    for i in 1:(length(v)-1)
        if v[i] >= threshold && v[i+1] < threshold
            return i+1
        end
    end
    return 0
end

"""
    _calculate_fwhm_delta_m(mz::AbstractVector{<:Real}, intensity::AbstractVector{<:Real}, peak_idx::Int) -> Float64

Calculates the Full Width at Half Maximum (FWHM) in m/z units (Δm) for a peak.
Returns `NaN` if FWHM cannot be determined.
"""
function _calculate_fwhm_delta_m(mz::AbstractVector{<:Real}, intensity::AbstractVector{<:Real}, peak_idx::Int)
    peak_height = Float64(intensity[peak_idx])
    half_max = peak_height / 2
    
    # Find left half-maximum point
    left_idx = find_last_below(intensity[1:peak_idx], half_max)
    if left_idx == 0 || left_idx == length(intensity[1:peak_idx])
        return NaN
    end
    
    # Linear interpolation for left FWHM m/z
    x1, x2 = Float64(mz[left_idx]), Float64(mz[left_idx+1])
    y1, y2 = Float64(intensity[left_idx]), Float64(intensity[left_idx+1])
    denominator = y2 - y1
    if denominator == 0
        left_fwhm_mz = NaN
    else
        left_fwhm_mz = x1 + (x2 - x1) * (half_max - y1) / denominator
    end
    
    # Find right half-maximum point
    right_slice = intensity[peak_idx:end]
    right_offset = find_first_below(right_slice, half_max)
    if right_offset == 0 || right_offset == length(right_slice)
        return NaN
    end
    
    right_idx = peak_idx + right_offset - 1
    x1, x2 = Float64(mz[right_idx-1]), Float64(mz[right_idx])
    y1, y2 = Float64(intensity[right_idx-1]), Float64(intensity[right_idx])
    denominator = y2 - y1
    if denominator == 0
        right_fwhm_mz = NaN
    else
        right_fwhm_mz = x1 + (x2 - x1) * (half_max - y1) / denominator
    end
    
    return right_fwhm_mz - left_fwhm_mz
end

"""
    _fit_gaussian_and_r2(mz::AbstractVector{<:Real}, intensity::AbstractVector{<:Real}, peak_idx::Int, half_window::Int) -> Float64

Estimates Gaussian parameters for a peak and returns a pseudo R^2 value.
This is an approximation and not a full non-linear least squares fit.
"""
function _fit_gaussian_and_r2(mz::AbstractVector{<:Real}, intensity::AbstractVector{<:Real}, peak_idx::Int, half_window::Int)
    n = length(mz)
    if n < 3 || peak_idx <= 0 || peak_idx > n
        return 0.0
    end

    # Define the region around the peak
    start_idx = max(1, peak_idx - half_window)
    end_idx = min(n, peak_idx + half_window)
    
    # Ensure there's enough data to fit
    if (end_idx - start_idx + 1) < 3
        return 0.0
    end

    x_data = mz[start_idx:end_idx]
    y_data = intensity[start_idx:end_idx]

    # Estimate Gaussian parameters
    # Amplitude (A): peak intensity
    A_est = intensity[peak_idx]
    # Mean (μ): m/z at peak intensity
    mu_est = mz[peak_idx]
    # Standard deviation (σ): related to FWHM. FWHM = 2 * sqrt(2 * ln(2)) * σ ≈ 2.355 * σ
    # So, σ ≈ FWHM / 2.355
    fwhm_delta_m = _calculate_fwhm_delta_m(mz, intensity, peak_idx)
    if isnan(fwhm_delta_m) || fwhm_delta_m <= 0
        return 0.0 # Cannot estimate sigma without a valid FWHM
    end
    sigma_est = fwhm_delta_m / 2.355

    # If sigma is too small, it might lead to division by zero or very sharp peaks
    if sigma_est < eps(Float64)
        return 0.0
    end

    # Gaussian function
    gaussian(x, A, mu, sigma) = A * exp.(-(x .- mu).^2 ./ (2 * sigma^2))

    # Generate estimated Gaussian curve
    y_est = gaussian(x_data, A_est, mu_est, sigma_est)

    # Calculate pseudo R-squared
    # R^2 = 1 - (SS_res / SS_tot)
    # SS_res = sum((y_data - y_est).^2)
    # SS_tot = sum((y_data - mean(y_data)).^2)

    SS_res = sum((y_data .- y_est).^2)
    SS_tot = sum((y_data .- mean(y_data)).^2)

    if SS_tot == 0
        return 1.0 # Perfect fit if all y_data are the same
    end

    r_squared = 1.0 - (SS_res / SS_tot)
    return max(0.0, r_squared) # R^2 can be negative if fit is worse than mean, cap at 0
end

"""
    calculate_robust_fwhm(mz::AbstractVector{<:Real}, intensity::AbstractVector{<:Real}, peak_idx::Int) -> Float64

A more robust FWHM calculation that handles edge cases better.
"""
function calculate_robust_fwhm(mz::AbstractVector{<:Real}, intensity::AbstractVector{<:Real}, peak_idx::Int)
    n = length(mz)
    if n < 5 || peak_idx < 3 || peak_idx > n-2
        return NaN
    end
    
    peak_height = Float64(intensity[peak_idx])
    half_max = peak_height / 2.0
    
    # Find left half-maximum with bounds checking
    left_idx = peak_idx
    while left_idx > 1 && intensity[left_idx] >= half_max
        left_idx -= 1
    end
    
    if left_idx == 1 || left_idx >= n-1
        return NaN
    end
    
    # Linear interpolation for left FWHM
    x1, x2 = Float64(mz[left_idx]), Float64(mz[left_idx+1])
    y1, y2 = Float64(intensity[left_idx]), Float64(intensity[left_idx+1])
    
    if y2 == y1  # Avoid division by zero
        left_fwhm_mz = x1
    else
        left_fwhm_mz = x1 + (x2 - x1) * (half_max - y1) / (y2 - y1)
    end
    
    # Find right half-maximum
    right_idx = peak_idx
    while right_idx < n && intensity[right_idx] >= half_max
        right_idx += 1
    end
    
    if right_idx == n || right_idx <= 2
        return NaN
    end
    
    # Linear interpolation for right FWHM
    x1, x2 = Float64(mz[right_idx-1]), Float64(mz[right_idx])
    y1, y2 = Float64(intensity[right_idx-1]), Float64(intensity[right_idx])
    
    if y2 == y1  # Avoid division by zero
        right_fwhm_mz = x1
    else
        right_fwhm_mz = x1 + (x2 - x1) * (half_max - y1) / (y2 - y1)
    end
    
    fwhm = right_fwhm_mz - left_fwhm_mz
    
    # Validate result
    if fwhm <= 0 || !isfinite(fwhm) || fwhm > 1.0  # Unreasonably large
        return NaN
    end
    
    return fwhm
end

"""
    main_precalculation(msi_data::MSIData; ...)

Runs the non-verbose pre-analysis pipeline and returns a dictionary of recommended 
preprocessing parameters based on data characteristics and heuristics.

This function serves as a quiet entry point to the analysis engine, translating the
analytical results into a concrete set of parameters for a preprocessing pipeline.
It also categorizes parameters that cannot be automatically determined.

# Arguments
- `msi_data::MSIData`: The main MSI data object.
- `reference_peaks::Dict`: Optional dictionary of reference m/z values for mass accuracy analysis.
- `region_masks::Dict`: Optional dictionary of named `BitMatrix` masks for regional analysis.
- `sample_size::Int`: The number of spectra to sample for statistical analysis.
- `mask_path::String`: Optional path to a PNG mask file to restrict the analysis to a specific ROI.
- `spectrum_indices::AbstractVector{Int}`: Optional vector of spectrum indices to restrict analysis to.

# Returns
- A `Dict` with two keys:
    - `"recommended_parameters"`: A `Dict{Symbol, Any}` of suggested parameter values.
    - `"unsupported_parameters"`: A `Dict` categorizing parameters that could not be determined.
"""
function main_precalculation(msi_data::MSIData; 
                             reference_peaks::Dict{Float64, String}=Dict{Float64, String}(),
                             region_masks::Dict{Symbol, BitMatrix}=Dict{Symbol, BitMatrix}(),
                             sample_size::Int=100,
                             mask_path::Union{String, Nothing}=nothing,
                             spectrum_indices::Union{AbstractVector{Int}, Nothing}=nothing)::Dict
    
    # --- Run analysis pipeline quietly ---
    local analysis_results
    original_stdout = stdout
    # Redirect stdout to the system's null device to robustly silence output
    null_stream = open(Sys.iswindows() ? "nul" : "/dev/null", "w")
    redirect_stdout(null_stream)
    try
        analysis_results = run_preprocessing_analysis(msi_data,
            reference_peaks=reference_peaks,
            region_masks=region_masks,
            sample_size=sample_size,
            mask_path=mask_path,
            spectrum_indices=spectrum_indices
        )
    finally
        redirect_stdout(original_stdout)
        close(null_stream)
    end

    if isempty(analysis_results)
        @warn "Preprocessing analysis returned no results. Cannot generate recommendations."
        return Dict() # Return an empty dictionary if no results
    end
    
    # --- Safely get nested dictionaries ---
    recs = get(analysis_results, :recommendations, Dict())
    signal_analysis = get(analysis_results, :signal_analysis, Dict())
    peak_analysis = get(analysis_results, :peak_analysis, Dict())
    mass_accuracy = get(analysis_results, :mass_accuracy, nothing) # Can be nothing
    inst_analysis = get(analysis_results, :instrument_analysis, Dict())

    # Initialize parameter dictionaries for each step
    stab_params = Dict{Symbol, Any}()
    cal_params = Dict{Symbol, Any}()
    sm_params = Dict{Symbol, Any}()
    bc_params = Dict{Symbol, Any}()
    norm_params = Dict{Symbol, Any}()
    pp_params = Dict{Symbol, Any}()
    pa_params = Dict{Symbol, Any}()
    ps_params = Dict{Symbol, Any}()
    pb_params = Dict{Symbol, Any}()

    # --- Populate Parameters for each step ---
    # Stabilization
    if !isempty(recs) && haskey(recs, :stabilization)
        stab_rec = recs[:stabilization]
        stab_params[:method] = get(stab_rec, :method, :sqrt)
    else
        stab_params[:method] = :sqrt # Default
    end

    # Calibration & Alignment (Note: These are intertwined in the current logic)
    calibration_required = false
    mean_ppm_error = NaN
    suggested_bin_tol = NaN
    if mass_accuracy !== nothing
        mean_ppm_error = get(get(mass_accuracy, :global_accuracy, Dict()), :mean_ppm_error, NaN)
        suggested_bin_tol = get(mass_accuracy, :suggested_bin_tolerance, NaN)
    end
    
    if !isempty(recs) && haskey(recs, :alignment) && get(recs[:alignment], :required, false)
        calibration_required = true
        cal_params[:method] = :internal_standards
        cal_params[:fit_order] = 2 # Default from struct
        if isfinite(suggested_bin_tol)
             cal_params[:ppm_tolerance] = suggested_bin_tol
        else
             cal_params[:ppm_tolerance] = nothing
        end
        cal_params[:internal_standards] = nothing # User input dependent
        cal_params[:base_peak_mz_references] = nothing # User input dependent

        if isfinite(mean_ppm_error)
            pa_params[:method] = mean_ppm_error > 30.0 ? :lowess : :linear
        else
            pa_params[:method] = :lowess # Default
        end

        tic_cv = get(signal_analysis, :tic_cv, NaN)
        if isfinite(tic_cv) && get(pa_params, :method, :none) == :lowess
            pa_params[:span] = round(max(0.3, min(0.8, 1.0 - tic_cv / 2)), digits=2)
        else
            pa_params[:span] = nothing
        end
        
        if isfinite(suggested_bin_tol)
             pa_params[:tolerance] = suggested_bin_tol
             pa_params[:tolerance_unit] = :ppm
        else
             pa_params[:tolerance] = nothing
             pa_params[:tolerance_unit] = :ppm # Default
        end
        pa_params[:max_shift_ppm] = get(recs[:alignment], :max_ppm_shift, 50.0)
        pa_params[:min_matched_peaks] = nothing # User input dependent
    else
        cal_params[:method] = :none
        cal_params[:ppm_tolerance] = nothing
        cal_params[:fit_order] = nothing
        cal_params[:internal_standards] = nothing
        cal_params[:base_peak_mz_references] = nothing

        pa_params[:method] = :none
        pa_params[:span] = nothing
        pa_params[:tolerance] = nothing
        pa_params[:tolerance_unit] = :ppm
        pa_params[:max_shift_ppm] = nothing
        pa_params[:min_matched_peaks] = nothing
    end

    # Smoothing
    if !isempty(recs) && haskey(recs, :smoothing)
        sm_rec = recs[:smoothing]
        if get(sm_rec, :method, "") == "Savitzky-Golay"
            sm_params[:method] = :savitzky_golay
            sm_params[:window] = get(sm_rec, :window_size, nothing)
            sm_params[:order] = get(sm_rec, :polynomial_order, nothing)
        else
            sm_params[:method] = :none
            sm_params[:window] = nothing
            sm_params[:order] = nothing
        end
    else
        sm_params[:method] = :none
        sm_params[:window] = nothing
        sm_params[:order] = nothing
    end
    
    # Baseline Correction
    if !isempty(recs) && haskey(recs, :baseline_correction)
        bl_rec = recs[:baseline_correction]
        if get(bl_rec, :method, "") == "SNIP"
             bc_params[:method] = :snip
             bc_params[:iterations] = get(bl_rec, :iterations, nothing)
        else
            bc_params[:method] = :none
            bc_params[:iterations] = nothing
        end
    else
        bc_params[:method] = :none
        bc_params[:iterations] = nothing
    end

    if get(inst_analysis, :acquisition_mode, :unknown) == :profile
        mean_fwhm_ppm = get(peak_analysis, :mean_fwhm_ppm, NaN)
        avg_mz_step = get(inst_analysis, :average_mz_step, NaN)
        if isfinite(mean_fwhm_ppm) && isfinite(avg_mz_step) && avg_mz_step > 0
            fwhm_mz = 500.0 * mean_fwhm_ppm / 1e6 # At typical m/z 500
            bc_params[:window] = ceil(Int, fwhm_mz / avg_mz_step * 2)
        else
            bc_params[:window] = nothing
        end
    else
        bc_params[:window] = nothing
    end

    # Normalization
    if !isempty(recs) && haskey(recs, :normalization)
        method = get(recs[:normalization], :method, "")
        if method == "TIC"
            norm_params[:method] = :tic
        elseif method == "RMS"
            norm_params[:method] = :rms
        else
            norm_params[:method] = :none
        end
    else
        norm_params[:method] = :none
    end

    # Peak Picking
    # Robust method selection based on acquisition mode
    acquisition_mode = get(inst_analysis, :acquisition_mode, :unknown)
    pp_params[:method] = acquisition_mode == :profile ? :profile : :centroid

    if acquisition_mode == :centroid
        # Much more permissive parameters for centroid data
        pp_params[:snr_threshold] = 2.0  # Lower for centroid
        pp_params[:min_peak_width_ppm] = 0.0    # No minimum width
        pp_params[:max_peak_width_ppm] = 200.0  # Very wide maximum
        pp_params[:min_peak_shape_r2] = 0.0     # Disable shape filtering
        
        # Much lower prominence threshold for centroid
        estimated_noise = get(signal_analysis, :noise_mean, NaN)
        if isfinite(estimated_noise)
            pp_params[:min_peak_prominence] = max(estimated_noise * 0.5, 0.001)  # Much lower
        else
            pp_params[:min_peak_prominence] = 0.001  # Very permissive
        end
        
        pp_params[:half_window] = 2  # Smaller window for centroid data
        pp_params[:merge_peaks_tolerance] = 10.0  # More permissive merging
    else # Profile mode logic
        if !isempty(recs) && haskey(recs, :peak_picking)
            pk_rec = recs[:peak_picking]
            pp_params[:snr_threshold] = get(pk_rec, :snr_threshold, 2.0) # Default to 2.0
            pp_params[:min_peak_width_ppm] = get(pk_rec, :min_peak_width_ppm, nothing)
            pp_params[:max_peak_width_ppm] = get(pk_rec, :max_peak_width_ppm, nothing)
        else
            pp_params[:snr_threshold] = 2.0 # Default to 2.0
            pp_params[:min_peak_width_ppm] = nothing
            pp_params[:max_peak_width_ppm] = nothing
        end
        
        # Robust prominence calculation with safety cap for profile
        estimated_noise = get(signal_analysis, :noise_mean, NaN)
        if isfinite(estimated_noise)
            calculated_prominence = round(estimated_noise * 2, digits=4)
            pp_params[:min_peak_prominence] = min(calculated_prominence, 0.005) 
        else
            pp_params[:min_peak_prominence] = 0.005 
        end

        if isfinite(suggested_bin_tol)
            pp_params[:merge_peaks_tolerance] = round(suggested_bin_tol / 2, digits=4)
        else
            pp_params[:merge_peaks_tolerance] = nothing
        end

        # Robust half_window calculation with safety floor for profile
        mean_fwhm_ppm = get(peak_analysis, :mean_fwhm_ppm, NaN)
        avg_mz_step = get(inst_analysis, :average_mz_step, NaN)
        if isfinite(mean_fwhm_ppm) && isfinite(avg_mz_step) && avg_mz_step > 0
            fwhm_mz = 500.0 * mean_fwhm_ppm / 1e6 # At typical m/z 500
            window_points = fwhm_mz / avg_mz_step
            calculated_half_window = ceil(Int, window_points / 2)
            pp_params[:half_window] = max(calculated_half_window, 3)
        else
            pp_params[:half_window] = 5
        end
        
        # Robust R^2 calculation with floor for profile
        mean_r2 = get(peak_analysis, :mean_gaussian_r2, NaN)
        if isfinite(mean_r2)
            pp_params[:min_peak_shape_r2] = round(max(0.0, mean_r2 * 0.8), digits=2)
        else
            pp_params[:min_peak_shape_r2] = 0.0
        end
    end


    # Peak Selection
    if acquisition_mode == :centroid
        # Much more permissive parameters for centroid data
        ps_params[:min_snr] = 1.5  # Even lower than picking threshold
        ps_params[:min_fwhm_ppm] = 0.0      # No minimum
        ps_params[:max_fwhm_ppm] = 500.0    # Very wide maximum
        ps_params[:min_shape_r2] = 0.0      # Disable shape filtering
        ps_params[:frequency_threshold] = nothing # User input dependent / Hard to determine
        ps_params[:correlation_threshold] = nothing # Hard to determine
    else # Profile mode logic
        if haskey(pp_params, :snr_threshold) && pp_params[:snr_threshold] !== nothing
            ps_params[:min_snr] = pp_params[:snr_threshold]
        else
            ps_params[:min_snr] = nothing
        end
        if !isempty(peak_analysis)
            mean_fwhm = get(peak_analysis, :mean_fwhm_ppm, NaN)
            if isfinite(mean_fwhm)
                ps_params[:min_fwhm_ppm] = round(mean_fwhm * 0.5, digits=2)
                ps_params[:max_fwhm_ppm] = round(mean_fwhm * 2.5, digits=2)
            else
                ps_params[:min_fwhm_ppm] = nothing
                ps_params[:max_fwhm_ppm] = nothing
            end
            mean_r2 = get(peak_analysis, :mean_gaussian_r2, NaN)
            if isfinite(mean_r2)
                ps_params[:min_shape_r2] = round(max(0.0, mean_r2 * 0.8), digits=2)
            else
                ps_params[:min_shape_r2] = 0.0 # Adjusted fallback
            end
        else
            ps_params[:min_fwhm_ppm] = nothing
            ps_params[:max_fwhm_ppm] = nothing
            ps_params[:min_shape_r2] = nothing
        end
        ps_params[:frequency_threshold] = nothing 
        ps_params[:correlation_threshold] = nothing 
    end


    # Peak Binning
    if !isempty(recs) && haskey(recs, :binning)
        bin_rec = recs[:binning]
        if get(bin_rec, :method, "") == "adaptive"
            pb_params[:method] = :adaptive
            bin_width = get(bin_rec, :bin_width_ppm, NaN)
            if isfinite(bin_width)
                pb_params[:tolerance] = bin_width
                pb_params[:max_bin_width_ppm] = round(bin_width * 3, digits=2)
            else
                pb_params[:tolerance] = nothing
                pb_params[:max_bin_width_ppm] = nothing
            end
            pb_params[:tolerance_unit] = :ppm
            pb_params[:min_peak_per_bin] = get(bin_rec, :min_peaks_per_bin, nothing)
            pb_params[:intensity_weighted_centers] = true # Default from struct
            pb_params[:num_uniform_bins] = nothing # User input dependent
            pb_params[:frequency_threshold] = nothing # Hard to determine
        else
            pb_params[:method] = :none
            pb_params[:tolerance] = nothing
            pb_params[:max_bin_width_ppm] = nothing
            pb_params[:tolerance_unit] = nothing
            pb_params[:min_peak_per_bin] = nothing
            pb_params[:intensity_weighted_centers] = true
            pb_params[:num_uniform_bins] = nothing
            pb_params[:frequency_threshold] = nothing
        end
    else
        pb_params[:method] = :none
        pb_params[:tolerance] = nothing
        pb_params[:max_bin_width_ppm] = nothing
        pb_params[:tolerance_unit] = nothing
        pb_params[:min_peak_per_bin] = nothing
        pb_params[:intensity_weighted_centers] = true
        pb_params[:num_uniform_bins] = nothing
        pb_params[:frequency_threshold] = nothing
    end

    return Dict(
        :Stabilization => stab_params,
        :Calibration => cal_params,
        :Smoothing => sm_params,
        :BaselineCorrection => bc_params,
        :Normalization => norm_params,
        :PeakPicking => pp_params,
        :PeakAlignment => pa_params,
        :PeakSelection => ps_params,
        :PeakBinning => pb_params
    )
end