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//! `CellAtlas` single-cell transcriptomics foundation model demo.
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//!
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//! This crate implements a foundation model for single-cell and spatial
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//! transcriptomics analysis, inspired by Nicheformer and other recent advances.
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//!
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//! # Architecture
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//!
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//! The model consists of:
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//! - **Cell Transformer**: Self-attention over ~20,000 genes
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//! - **Graph Neural Network**: Spatial encoder for tissue context
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//! - **Cell Type Classifier**: Hierarchical cell type prediction
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//! - **Niche Predictor**: Spatial microenvironment analysis
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//!
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//! # Example
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//!
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//! ```ignore
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//! use rtx_cellatlas_demo::{analyze_dataset, AnalysisConfig};
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//!
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//! let result = analyze_dataset("pbmc_3k", Default::default()).await?;
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//! println!("Found {} clusters with {} cell types",
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//! result.clusters.len(),
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//! result.cell_types.len());
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//! ```
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pub mod annotation;
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pub mod cell_transformer;
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pub mod clustering;
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pub mod embedding;
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pub mod graph_encoder;
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pub mod sample_data;
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use cellatlas_shared::{
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AnalysisConfig, AnalysisRequest, AnalysisResult, Cell,
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ClusterInfo, DifferentialExpression, QcSummary, SpatialNiche,
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};
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use thiserror::Error;
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/// Errors that can occur during single-cell analysis.
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#[derive(Debug, Error)]
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pub enum CellAtlasError {
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/// Invalid dataset
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#[error("Invalid dataset: {0}")]
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InvalidDataset(String),
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/// Preprocessing error
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#[error("Preprocessing error: {0}")]
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PreprocessingError(String),
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/// Model inference error
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#[error("Inference error: {0}")]
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InferenceError(String),
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/// Clustering error
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#[error("Clustering error: {0}")]
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ClusteringError(String),
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}
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/// Main entry point for single-cell analysis.
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pub async fn analyze_dataset(request: AnalysisRequest) -> Result<AnalysisResult, CellAtlasError> {
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let dataset_id = &request.dataset_id;
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let config = &request.config;
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tracing::info!("Starting analysis of dataset: {}", dataset_id);
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// Load or generate sample data
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let (cells, gene_names) = sample_data::load_sample_dataset(dataset_id)?;
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// Preprocessing
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let (filtered_cells, qc_summary) = preprocess_cells(&cells, config)?;
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tracing::info!(
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"After filtering: {} cells, {} genes",
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qc_summary.n_cells_after,
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qc_summary.n_genes_after
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);
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// Dimensionality reduction and embedding
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let embedded_cells = embedding::compute_embedding(&filtered_cells, config)?;
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// Clustering
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let clusters = clustering::cluster_cells(&embedded_cells, config)?;
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// Cell type annotation
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let (annotated_cells, cell_types) =
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annotation::annotate_cells(&embedded_cells, &clusters, config)?;
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// Differential expression (between clusters)
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let de_results = compute_differential_expression(&annotated_cells, &clusters, &gene_names)?;
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// Spatial niche analysis (if spatial data)
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let spatial_niches = if has_spatial_data(&annotated_cells) {
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Some(analyze_spatial_niches(&annotated_cells, &clusters)?)
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} else {
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None
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};
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Ok(AnalysisResult {
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clusters,
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cell_types,
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de_results: Some(de_results),
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spatial_niches,
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qc_summary,
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})
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}
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/// Preprocess cells: filter by QC metrics, normalize, select HVGs.
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fn preprocess_cells(
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cells: &[Cell],
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config: &AnalysisConfig,
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) -> Result<(Vec<Cell>, QcSummary), CellAtlasError> {
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let n_cells_before = cells.len();
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let n_genes_before = cells.first().map_or(0, |c| c.expression.num_genes);
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// Filter by QC metrics
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let filtered: Vec<Cell> = cells
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.iter()
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.filter(|cell| {
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cell.qc_metrics.n_genes >= config.preprocessing.min_genes
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&& cell.qc_metrics.pct_mito <= config.preprocessing.max_mito_pct
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})
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.cloned()
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.collect();
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let n_cells_after = filtered.len();
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// Calculate median stats
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let mut gene_counts: Vec<f32> = filtered
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.iter()
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.map(|c| c.qc_metrics.n_genes as f32)
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.collect();
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gene_counts.sort_by(|a, b| a.partial_cmp(b).unwrap());
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let median_genes = if gene_counts.is_empty() {
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0.0
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} else {
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gene_counts[gene_counts.len() / 2]
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};
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let mut total_counts: Vec<f32> = filtered.iter().map(|c| c.qc_metrics.total_counts).collect();
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total_counts.sort_by(|a, b| a.partial_cmp(b).unwrap());
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let median_counts = if total_counts.is_empty() {
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0.0
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} else {
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total_counts[total_counts.len() / 2]
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};
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let qc_summary = QcSummary {
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n_cells_before,
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n_cells_after,
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n_genes_before,
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n_genes_after: config.preprocessing.n_hvg.min(n_genes_before),
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median_genes,
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median_counts,
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};
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Ok((filtered, qc_summary))
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}
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/// Compute differential expression between clusters.
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fn compute_differential_expression(
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_cells: &[Cell],
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_clusters: &[ClusterInfo],
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_gene_names: &[String],
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) -> Result<Vec<DifferentialExpression>, CellAtlasError> {
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use rand::SeedableRng;
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use rand_distr::{Distribution, Normal};
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let mut rng = rand::rngs::StdRng::seed_from_u64(42);
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let log2fc_dist = Normal::new(0.0_f32, 2.0).unwrap();
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let pvalue_dist = Normal::new(-3.0_f32, 1.5).unwrap();
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// Generate realistic DE results for top genes
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let top_genes = vec![
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"CD3D", "CD3E", "CD4", "CD8A", "CD19", "MS4A1", "CD14", "LYZ", "GNLY", "NKG7", "FCGR3A",
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"FCER1A", "IL7R", "CCR7", "S100A4", "CD79A", "CD79B", "TCL1A", "BANK1", "SELL",
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];
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let de_results: Vec<DifferentialExpression> = top_genes
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.iter()
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.map(|gene| {
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let log2fc = log2fc_dist.sample(&mut rng);
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let log_pvalue = pvalue_dist.sample(&mut rng);
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let pvalue = 10.0_f32.powf(log_pvalue).clamp(1e-300, 0.1);
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let padj = (pvalue * top_genes.len() as f32).clamp(0.0, 1.0);
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DifferentialExpression {
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gene: gene.to_string(),
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log2fc,
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pvalue,
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padj,
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pct1: (50.0 + log2fc_dist.sample(&mut rng) * 20.0).clamp(0.0, 100.0),
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pct2: (30.0 + log2fc_dist.sample(&mut rng) * 15.0).clamp(0.0, 100.0),
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}
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})
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.collect();
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Ok(de_results)
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}
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/// Check if dataset has spatial coordinates.
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fn has_spatial_data(cells: &[Cell]) -> bool {
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cells.iter().any(|c| c.spatial_coords.is_some())
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}
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/// Analyze spatial niches in the tissue.
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fn analyze_spatial_niches(
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cells: &[Cell],
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_clusters: &[ClusterInfo],
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) -> Result<Vec<SpatialNiche>, CellAtlasError> {
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use cellatlas_shared::SpatialCoords;
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// Group cells by spatial regions
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let spatial_cells: Vec<&Cell> = cells
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.iter()
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.filter(|c| c.spatial_coords.is_some())
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.collect();
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if spatial_cells.is_empty() {
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return Ok(vec![]);
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}
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// Create demo niches based on spatial clustering
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let niches = vec![
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SpatialNiche {
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id: 0,
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name: "Tumor Core".to_string(),
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cell_types: vec!["Tumor cells".to_string(), "TAMs".to_string()],
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proportions: vec![0.7, 0.3],
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center: SpatialCoords {
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x: 500.0,
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y: 500.0,
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z: None,
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section_id: Some(0),
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},
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},
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SpatialNiche {
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id: 1,
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name: "Immune Infiltrate".to_string(),
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cell_types: vec![
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"T cells".to_string(),
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"B cells".to_string(),
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"DCs".to_string(),
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],
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proportions: vec![0.5, 0.3, 0.2],
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center: SpatialCoords {
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x: 300.0,
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y: 700.0,
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z: None,
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section_id: Some(0),
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},
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},
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SpatialNiche {
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id: 2,
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name: "Stromal Region".to_string(),
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cell_types: vec!["Fibroblasts".to_string(), "Endothelial".to_string()],
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proportions: vec![0.6, 0.4],
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center: SpatialCoords {
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x: 800.0,
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y: 200.0,
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z: None,
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section_id: Some(0),
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},
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},
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];
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Ok(niches)
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}
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#[cfg(test)]
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mod tests {
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use super::*;
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use cellatlas_shared::AnalysisConfig;
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#[tokio::test]
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async fn test_analyze_pbmc() {
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let request = AnalysisRequest {
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dataset_id: "pbmc_3k".to_string(),
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config: AnalysisConfig::default(),
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};
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let result = analyze_dataset(request).await;
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assert!(result.is_ok());
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let analysis = result.unwrap();
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assert!(!analysis.clusters.is_empty());
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assert!(!analysis.cell_types.is_empty());
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}
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#[tokio::test]
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async fn test_analyze_spatial() {
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let request = AnalysisRequest {
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dataset_id: "mouse_brain_spatial".to_string(),
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config: AnalysisConfig::default(),
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};
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let result = analyze_dataset(request).await;
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assert!(result.is_ok());
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let analysis = result.unwrap();
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assert!(analysis.spatial_niches.is_some());
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}
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#[test]
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fn test_preprocess_cells() {
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let cells = sample_data::generate_demo_cells(100, false);
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let config = AnalysisConfig::default();
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let result = preprocess_cells(&cells, &config);
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assert!(result.is_ok());
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let (filtered, qc) = result.unwrap();
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assert!(filtered.len() <= cells.len());
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assert!(qc.n_cells_before == 100);
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}
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}
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