""" N-level foundation model wrappers for Kukanja. These extend the existing FM model classes to support N classification heads. """ import torch import torch.nn as nn class ClsDecoder(nn.Module): """Shared classification decoder head.""" def __init__(self, d_model: int, n_cls: int, nlayers: int = 3): super().__init__() layers = [] for _ in range(nlayers - 1): layers += [nn.Linear(d_model, d_model), nn.LayerNorm(d_model), nn.LeakyReLU()] layers.append(nn.Linear(d_model, n_cls)) self.net = nn.Sequential(*layers) def forward(self, x): return self.net(x) class GeneformerNLevel(nn.Module): """ N-level Geneformer wrapper. Loads pretrained backbone from GeneformerForAnnotation, replaces heads with N-level ModuleList. """ def __init__(self, code_dir, weights_path, gene_names, output_num, dropout=0.2, freeze_backbone=False, max_seq_len=1024): super().__init__() from src.models.geneformer.geneformer_annotation import GeneformerForAnnotation # Create base model with dummy 3-level output (just to load backbone) dummy_out = output_num[:3] if len(output_num) >= 3 else output_num + [2] * (3 - len(output_num)) self._base = GeneformerForAnnotation( code_dir=code_dir, weights_path=weights_path, gene_names=gene_names, output_num=dummy_out, dropout=dropout, freeze_backbone=freeze_backbone, max_seq_len=max_seq_len, ) d_model = self._base.d_model # Replace with N-level heads self.heads = nn.ModuleList([ ClsDecoder(d_model, n) for n in output_num ]) # Remove old heads to avoid confusion del self._base.cls_head_class del self._base.cls_head_subclass del self._base.cls_head_supertype def forward(self, X): input_ids, attention_mask = self._base._tokenize(X) outputs = self._base.backbone(input_ids=input_ids, attention_mask=attention_mask) last_hidden = outputs.last_hidden_state gene_attn_mask = attention_mask.clone() gene_attn_mask[:, 0] = 0.0 count = gene_attn_mask.sum(dim=1, keepdim=True).clamp(min=1.0) cell_emb = (last_hidden * gene_attn_mask.unsqueeze(-1)).sum(dim=1) / count logits = [h(cell_emb) for h in self.heads] return logits, cell_emb class UCENLevel(nn.Module): """ N-level UCE wrapper. Loads pretrained backbone from UCEForAnnotation, replaces heads with N-level ModuleList. """ def __init__(self, model_dir, gene_names, output_num, dropout=0.2, freeze_backbone=False, species='human'): super().__init__() from src.models.uce.uce_annotation import UCEForAnnotation dummy_out = output_num[:3] if len(output_num) >= 3 else output_num + [2] * (3 - len(output_num)) self._base = UCEForAnnotation( model_dir=model_dir, gene_names=gene_names, output_num=dummy_out, dropout=dropout, freeze_backbone=freeze_backbone, ) # For mouse species, we need to override the species filter if species == 'mouse': self._override_species_mouse(model_dir, gene_names) d_model = self._base.d_model self.heads = nn.ModuleList([ ClsDecoder(d_model, n) for n in output_num ]) del self._base.cls_head_class del self._base.cls_head_subclass del self._base.cls_head_supertype def _override_species_mouse(self, model_dir, gene_names): """Override UCE's gene mapping to use mouse genes instead of human.""" import os, pickle import pandas as pd import torch import numpy as np chrom_csv = os.path.join(model_dir, 'species_chrom.csv') offsets_pkl = os.path.join(model_dir, 'species_offsets.pkl') chrom_df = pd.read_csv(chrom_csv) # Reconstruct spec_chrom codes the same way as base class chrom_df["spec_chrom"] = pd.Categorical( chrom_df["species"] + "_" + chrom_df["chromosome"].astype(str) ) mouse_df = chrom_df[chrom_df['species'] == 'mouse'].reset_index(drop=True) if mouse_df.empty: print("[UCE] WARNING: No mouse genes found in species_chrom.csv") return with open(offsets_pkl, 'rb') as f: offsets = pickle.load(f) mouse_offset = offsets.get('mouse', 0) # Build gene lookup (case-insensitive: UCE uses UPPERCASE, EAE uses Title Case) gene_to_info = {} for i, row in mouse_df.iterrows(): gene = row['gene_symbol'] gene_to_info[gene.upper()] = { "token_idx": mouse_offset + i, "chrom_code": int(mouse_df["spec_chrom"].cat.codes[i]), "start": int(row["start"]), } # Rebuild all four buffers from src.models.uce.uce_annotation import PAD_TOKEN_IDX token_idxs = [] chrom_codes = [] starts = [] valid_mask = [] for g in gene_names: info = gene_to_info.get(g.upper()) if info is None: token_idxs.append(PAD_TOKEN_IDX) chrom_codes.append(-1) starts.append(0) valid_mask.append(False) else: token_idxs.append(info["token_idx"]) chrom_codes.append(info["chrom_code"]) starts.append(info["start"]) valid_mask.append(True) valid_count = sum(valid_mask) print(f"[UCE-mouse] Gene coverage: {valid_count}/{len(gene_names)}") # Replace the base class buffers self._base._token_idxs = torch.tensor(token_idxs, dtype=torch.long) self._base._chrom_codes = torch.tensor(chrom_codes, dtype=torch.long) self._base._starts = torch.tensor(starts, dtype=torch.long) self._base._valid_mask = torch.tensor(valid_mask, dtype=torch.bool) self._base.register_buffer("_token_idxs", self._base._token_idxs) self._base.register_buffer("_chrom_codes", self._base._chrom_codes) self._base.register_buffer("_starts", self._base._starts) self._base.register_buffer("_valid_mask", self._base._valid_mask) def forward(self, X): # Bypass base forward (heads deleted), call backbone directly import torch.nn.functional as F sentences, mask = self._base._build_sentences(X) emb = self._base.pe_embedding(sentences) emb = F.normalize(emb, dim=2) _, cell_emb = self._base.backbone(emb, mask=mask) logits = [h(cell_emb) for h in self.heads] return logits, cell_emb class ScGPTNLevel(nn.Module): """ N-level scGPT wrapper. Converts gene_names to vocab IDs, loads pretrained backbone from scGPTForAnnotation, replaces heads with N-level ModuleList. """ def __init__(self, ckpt_dir, gene_names, output_num, dropout=0.2, freeze_backbone=False): super().__init__() import json from pathlib import Path from src.models.scGPT.scGPT_annotation import scGPTForAnnotation # Convert gene names to vocab IDs ckpt_path = Path(ckpt_dir) with open(ckpt_path / "vocab.json") as f: vocab = json.load(f) gene_ids = [] valid = 0 for g in gene_names: if g in vocab: gene_ids.append(vocab[g]) valid += 1 else: gene_ids.append(vocab.get("", 0)) print(f"[scGPT] Gene coverage: {valid}/{len(gene_names)}") gene_ids_tensor = torch.tensor(gene_ids, dtype=torch.long) dummy_out = output_num[:3] if len(output_num) >= 3 else output_num + [2] * (3 - len(output_num)) self._base = scGPTForAnnotation( checkpoint_dir=ckpt_dir, gene_ids=gene_ids_tensor, output_num=dummy_out, dropout=dropout, freeze_backbone=freeze_backbone, ) d_model = self._base.d_model self.heads = nn.ModuleList([ ClsDecoder(d_model, n) for n in output_num ]) del self._base.cls_head_class del self._base.cls_head_subclass del self._base.cls_head_supertype def forward(self, X): # Bypass base forward (heads deleted), call backbone directly from src.models.scGPT.binning import scgpt_binning_torch batch_size = X.shape[0] device = X.device X_norm = torch.log1p(X) X_binned = scgpt_binning_torch(X_norm, n_bins=self._base.n_bins).float() cls_ids = X.new_full((batch_size, 1), self._base.cls_token_id, dtype=torch.long) cls_vals = X.new_zeros(batch_size, 1) gene_ids_exp = self._base.gene_ids.unsqueeze(0).expand(batch_size, -1) src = torch.cat([cls_ids, gene_ids_exp], dim=1) values = torch.cat([cls_vals, X_binned], dim=1) src_key_padding_mask = torch.zeros( batch_size, src.shape[1], dtype=torch.bool, device=device ) output = self._base.backbone(src, values, src_key_padding_mask) cell_emb = output["cell_emb"] logits = [h(cell_emb) for h in self.heads] return logits, cell_emb class StackNLevel(nn.Module): """ N-level Stack wrapper. Loads pretrained backbone from StackForAnnotation, replaces heads with N-level ModuleList. """ def __init__(self, checkpoint_path, gene_list_path, gene_names, output_num, dropout=0.2, freeze_backbone=False): super().__init__() from src.models.stack_model.stack_annotation import StackForAnnotation dummy_out = output_num[:3] if len(output_num) >= 3 else output_num + [2] * (3 - len(output_num)) self._base = StackForAnnotation( checkpoint_path=checkpoint_path, gene_list_path=gene_list_path, gene_names=gene_names, output_num=dummy_out, dropout=dropout, freeze_backbone=freeze_backbone, ) d_model = self._base.embed_dim self.heads = nn.ModuleList([ ClsDecoder(d_model, n) for n in output_num ]) del self._base.cls_head_class del self._base.cls_head_subclass del self._base.cls_head_supertype def forward(self, X): features = self._base._map_genes(X) features_log = torch.log1p(features) if self._base.freeze_backbone: with torch.no_grad(): tokens = self._base.backbone._reduce_and_tokenize(features_log) x = self._base.backbone._run_attention_layers(tokens) else: tokens = self._base.backbone._reduce_and_tokenize(features_log) x = self._base.backbone._run_attention_layers(tokens) cell_emb = x.reshape(X.shape[0], -1) logits = [h(cell_emb) for h in self.heads] return logits, cell_emb class ScSimilarityNLevel(nn.Module): """ N-level scSimilarity wrapper trained from scratch on the current gene panel. """ def __init__(self, n_genes, output_num, latent_dim=128, hidden_dim=None, dropout=0.5, input_dropout=0.4, freeze_backbone=False): super().__init__() from scimilarity.nn_models import Encoder if hidden_dim is None: hidden_dim = [512, 512] self.encoder = Encoder( n_genes=n_genes, latent_dim=latent_dim, hidden_dim=hidden_dim, dropout=dropout, input_dropout=input_dropout, ) self.freeze_backbone = freeze_backbone if freeze_backbone: for p in self.encoder.parameters(): p.requires_grad = False self.heads = nn.ModuleList([ ClsDecoder(latent_dim, n) for n in output_num ]) def forward(self, X): X_norm = torch.log1p(X) if self.freeze_backbone: with torch.no_grad(): cell_emb = self.encoder(X_norm) else: cell_emb = self.encoder(X_norm) logits = [h(cell_emb) for h in self.heads] return logits, cell_emb class NicheformerNLevel(nn.Module): """ N-level Nicheformer wrapper for human Kukanja datasets. """ def __init__(self, checkpoint_path, vocab_path, merfish_mean_path, gene_name_to_ens_path, gene_names, output_num, dropout=0.2, freeze_backbone=False, specie_token=5): super().__init__() from src.models.nicheformer.nicheformer_annotation import NicheformerForAnnotation dummy_out = output_num[:3] if len(output_num) >= 3 else output_num + [2] * (3 - len(output_num)) self._base = NicheformerForAnnotation( checkpoint_path=checkpoint_path, vocab_path=vocab_path, merfish_mean_path=merfish_mean_path, gene_name_to_ens_path=gene_name_to_ens_path, gene_names=gene_names, output_num=dummy_out, dropout=dropout, freeze_backbone=freeze_backbone, specie_token=specie_token, ) for head in [self._base.cls_head_class, self._base.cls_head_subclass, self._base.cls_head_supertype]: for p in head.parameters(): p.requires_grad = False d_model = self._base.d_model self.heads = nn.ModuleList([ ClsDecoder(d_model, n) for n in output_num ]) def forward(self, X): _, cell_emb = self._base(X) logits = [h(cell_emb) for h in self.heads] return logits, cell_emb class ScFoundationNLevel(nn.Module): """ N-level scFoundation wrapper. """ def __init__(self, model_path, config_path, gene_names, output_num, dropout=0.2, freeze_backbone=False, pool_type='all'): super().__init__() from src.models.scfoundation.scfoundation_annotation import ScFoundationForAnnotation dummy_out = output_num[:3] if len(output_num) >= 3 else output_num + [2] * (3 - len(output_num)) self._base = ScFoundationForAnnotation( model_path=model_path, config_path=config_path, gene_names=gene_names, output_num=dummy_out, dropout=dropout, freeze_backbone=freeze_backbone, pool_type=pool_type, ) for head in [self._base.cls_head_class, self._base.cls_head_subclass, self._base.cls_head_supertype]: for p in head.parameters(): p.requires_grad = False d_model = self._base.embed_dim self.heads = nn.ModuleList([ ClsDecoder(d_model, n) for n in output_num ]) def forward(self, X): cell_emb = self._base._encode(X) cell_emb = self._base.emb_norm(cell_emb) logits = [h(cell_emb) for h in self.heads] return logits, cell_emb