""" STELLAR-like Spatial GNN for hierarchical cell annotation. Architecture: 1. Build KNN spatial graph (precomputed) 2. Gene expression encoder (Linear → hidden) 3. GCN message passing layers (aggregate neighbor features) 4. Hierarchical classification heads (same residual design as mjm_1) 5. Reconstruction decoder The spatial graph encodes cell neighborhood structure — cells that are physically close share information through message passing, compensating for the limited gene panel in MERFISH data. """ import torch import torch.nn as nn import torch.nn.functional as F import numpy as np from scipy.spatial import cKDTree # ── Graph construction ────────────────────────────────────────────────────── def build_knn_graph(spatial_coords, k=15): """ Build a KNN spatial graph from 2D coordinates. Returns edge_index [2, E] as a LongTensor (COO format). """ tree = cKDTree(spatial_coords) _, indices = tree.query(spatial_coords, k=k + 1) # +1 because self is included n = len(spatial_coords) src = np.repeat(np.arange(n), k) dst = indices[:, 1:].flatten() # exclude self-loop edge_index = np.stack([src, dst], axis=0) return torch.from_numpy(edge_index).long() # ── GCN Layer (pure PyTorch) ──────────────────────────────────────────────── class GCNConv(nn.Module): """Simple GCN convolution: h' = D^{-1} A X W + b (mean aggregation).""" def __init__(self, in_dim, out_dim): super().__init__() self.linear = nn.Linear(in_dim, out_dim) def forward(self, x, edge_index): """ x: [N, in_dim] edge_index: [2, E] (src → dst) """ src, dst = edge_index N = x.size(0) # Transform h = self.linear(x) # [N, out_dim] # Aggregate (mean of neighbors) # Use scatter_mean via index_add agg = torch.zeros_like(h) agg.index_add_(0, dst, h[src]) # Degree normalization deg = torch.zeros(N, device=x.device) deg.index_add_(0, dst, torch.ones(dst.size(0), device=x.device)) deg = deg.clamp(min=1).unsqueeze(-1) agg = agg / deg return agg # ── Spatial GNN Model ─────────────────────────────────────────────────────── class SpatialGNN(nn.Module): """ STELLAR-inspired spatial GNN for hierarchical cell annotation. Pipeline: X [B, 140] → gene_encoder → h0 [B, hidden] h0 → GCN_1 → h1 → GCN_2 → h2 (spatial context aggregation) h2 → head_class → logits_class [B, 3] h2 → head_subclass → logits_subclass [B, 24] (+ residual from class) h2 → head_supertype→ logits_supertype [B, 137] (+ residual from subclass) h2 → recon_decoder → x_hat [B, 140] """ def __init__(self, input_dim=140, hidden_dim=256, latent_dim=128, n_gcn_layers=2, dropout=0.3, output_num=[3, 24, 137]): super().__init__() # Gene expression encoder self.gene_encoder = nn.Sequential( nn.Linear(input_dim, hidden_dim), nn.LayerNorm(hidden_dim), nn.SiLU(), nn.Dropout(dropout), ) # GCN layers self.gcn_layers = nn.ModuleList() self.gcn_norms = nn.ModuleList() for _ in range(n_gcn_layers): self.gcn_layers.append(GCNConv(hidden_dim, hidden_dim)) self.gcn_norms.append(nn.LayerNorm(hidden_dim)) self.gcn_dropout = nn.Dropout(dropout) # Projection to latent self.to_latent = nn.Linear(hidden_dim, latent_dim) # Hierarchical classification heads (with cross-level feature residual) dec_dim = latent_dim self.dec1 = nn.Sequential(nn.Linear(dec_dim, dec_dim), nn.SiLU(), nn.Dropout(dropout)) self.dec2 = nn.Sequential(nn.Linear(dec_dim, dec_dim), nn.SiLU(), nn.Dropout(dropout)) self.dec3 = nn.Sequential(nn.Linear(dec_dim, dec_dim), nn.SiLU(), nn.Dropout(dropout)) self.head1 = nn.Linear(dec_dim, output_num[0]) self.head2 = nn.Linear(dec_dim, output_num[1]) self.head3 = nn.Linear(dec_dim, output_num[2]) # Reconstruction self.recon_decoder = nn.Sequential( nn.Linear(latent_dim, hidden_dim), nn.SiLU(), nn.Linear(hidden_dim, input_dim), ) def forward(self, x, edge_index): """ Args: x: [N, input_dim] gene expression (log1p normalized) edge_index: [2, E] spatial KNN graph Returns: recon: [N, input_dim] logits: [logits_class, logits_subclass, logits_supertype] z: [N, latent_dim] """ # Encode gene expression h = self.gene_encoder(x) # GCN message passing with residual connections for gcn, norm in zip(self.gcn_layers, self.gcn_norms): h_new = gcn(h, edge_index) h = norm(h + h_new) # residual + norm h = F.silu(h) h = self.gcn_dropout(h) # Project to latent z = self.to_latent(h) # Hierarchical decoding with feature residuals c1 = self.dec1(z) logits1 = self.head1(c1) c2 = self.dec2(z) + c1 logits2 = self.head2(c2) c3 = self.dec3(z) + c2 logits3 = self.head3(c3) # Reconstruction recon = self.recon_decoder(z) return recon, [logits1, logits2, logits3], z