from typing import List, Dict, Optional, Union, Tuple import numpy as np from transformers import PreTrainedTokenizer from dataclasses import dataclass import torch import anndata as ad from scipy.sparse import issparse import numba import os import json from huggingface_hub import hf_hub_download import pandas as pd # Token IDs must match exactly with the original implementation PAD_TOKEN = 0 MASK_TOKEN = 1 CLS_TOKEN = 2 # These mappings preserve the exact token IDs from the original implementation MODALITY_DICT = { 'dissociated': 3, 'spatial': 4, } SPECIES_DICT = { 'human': 5, 'Homo sapiens': 5, 'Mus musculus': 6, 'mouse': 6, } TECHNOLOGY_DICT = { "merfish": 7, "MERFISH": 7, "cosmx": 8, "NanoString digital spatial profiling": 8, "Xenium": 9, "10x 5' v2": 10, "10x 3' v3": 11, "10x 3' v2": 12, "10x 5' v1": 13, "10x 3' v1": 14, "10x 3' transcription profiling": 15, "10x transcription profiling": 15, "10x 5' transcription profiling": 16, "CITE-seq": 17, "Smart-seq v4": 18, } def sf_normalize(X: np.ndarray) -> np.ndarray: """Size factor normalize to 10k counts.""" X = X.copy() counts = np.array(X.sum(axis=1)) # avoid zero division error counts += counts == 0. # normalize to 10000 counts scaling_factor = 10000. / counts if issparse(X): from scipy.sparse import sparsefuncs sparsefuncs.inplace_row_scale(X, scaling_factor) else: np.multiply(X, scaling_factor.reshape((-1, 1)), out=X) return X @numba.jit(nopython=True, nogil=True) def _sub_tokenize_data(x: np.ndarray, max_seq_len: int = -1, aux_tokens: int = 30) -> np.ndarray: """Tokenize the input gene vector.""" scores_final = np.empty((x.shape[0], max_seq_len if max_seq_len > 0 else x.shape[1])) for i, cell in enumerate(x): nonzero_mask = np.nonzero(cell)[0] sorted_indices = nonzero_mask[np.argsort(-cell[nonzero_mask])][:max_seq_len] sorted_indices = sorted_indices + aux_tokens if max_seq_len: scores = np.zeros(max_seq_len, dtype=np.int32) else: scores = np.zeros_like(cell, dtype=np.int32) scores[:len(sorted_indices)] = sorted_indices.astype(np.int32) scores_final[i, :] = scores return scores_final class NicheformerTokenizer(PreTrainedTokenizer): """Tokenizer for Nicheformer that handles single-cell data.""" model_input_names = ["input_ids", "attention_mask"] vocab_files_names = {"vocab_file": "vocab.json"} modality_dict = MODALITY_DICT species_dict = SPECIES_DICT technology_dict = TECHNOLOGY_DICT def _load_reference_model(self): """Load reference model for gene alignment.""" try: # Get the model name or path from the tokenizer repo_id = self.name_or_path if hasattr(self, "name_or_path") else "aletlvl/Nicheformer" # Download the reference model if not already cached model_path = hf_hub_download(repo_id=repo_id, filename="model.h5ad") return ad.read_h5ad(model_path) except Exception as e: print(f"Warning: Could not load reference model: {e}") return None def __init__( self, vocab_file=None, max_length: int = 1500, aux_tokens: int = 30, median_counts_per_gene: Optional[np.ndarray] = None, gene_names: Optional[List[str]] = None, technology_mean: Optional[Union[str, np.ndarray]] = None, **kwargs ): # Initialize base vocabulary self._vocabulary = { "[PAD]": PAD_TOKEN, "[MASK]": MASK_TOKEN, "[CLS]": CLS_TOKEN, } if vocab_file is not None: with open(vocab_file, 'r') as f: self._vocabulary.update(json.load(f)) else: # Add modality tokens for name, idx in self.modality_dict.items(): self._vocabulary[f"[MODALITY_{name}]"] = idx # Add species tokens for name, idx in self.species_dict.items(): if name in ["Homo sapiens", "Mus musculus"]: continue # Skip redundant names self._vocabulary[f"[SPECIES_{name}]"] = idx # Add technology tokens for name, idx in self.technology_dict.items(): if name in ["MERFISH", "10x transcription profiling"]: continue # Skip redundant names clean_name = name.lower().replace(" ", "_").replace("'", "_") self._vocabulary[f"[TECH_{clean_name}]"] = idx # Add gene tokens if provided if gene_names is not None: for i, gene in enumerate(gene_names): self._vocabulary[gene] = i + aux_tokens # Save vocabulary os.makedirs('to_hf', exist_ok=True) with open('to_hf/vocab.json', 'w') as f: json.dump(self._vocabulary, f, indent=4) super().__init__(**kwargs) self.max_length = max_length self.aux_tokens = aux_tokens self.median_counts_per_gene = median_counts_per_gene self.gene_names = gene_names self.name_or_path = kwargs.get('name_or_path', 'aletlvl/Nicheformer') # Set up special token mappings self._pad_token = "[PAD]" self._mask_token = "[MASK]" self._cls_token = "[CLS]" # Load technology mean if provided self.technology_mean = None if technology_mean is not None: self._load_technology_mean(technology_mean) def _load_technology_mean(self, technology_mean): """Load technology mean from file or array.""" if isinstance(technology_mean, str): try: self.technology_mean = np.load(technology_mean) print(f"Loaded technology mean from {technology_mean} with shape {self.technology_mean.shape}") except Exception as e: print(f"Warning: Could not load technology mean from {technology_mean}: {e}") elif isinstance(technology_mean, np.ndarray): self.technology_mean = technology_mean print(f"Using provided technology mean array with shape {self.technology_mean.shape}") else: print(f"Warning: Invalid technology_mean type: {type(technology_mean)}") def get_vocab(self) -> Dict[str, int]: """Returns the vocabulary mapping.""" return self._vocabulary.copy() def _tokenize(self, text: str) -> List[str]: """Tokenize text input.""" # This tokenizer doesn't handle text input directly raise NotImplementedError("This tokenizer only works with gene expression data") def _convert_token_to_id(self, token: str) -> int: """Convert token to ID.""" # First check special token mappings if token in self.modality_dict: return self.modality_dict[token] if token in self.species_dict: return self.species_dict[token] if token in self.technology_dict: return self.technology_dict[token] # Then check vocabulary return self._vocabulary.get(token, self._vocabulary["[PAD]"]) def _convert_id_to_token(self, index: int) -> str: """Convert ID to token.""" # First check special token mappings for token, idx in self.modality_dict.items(): if idx == index: return token for token, idx in self.species_dict.items(): if idx == index: return token for token, idx in self.technology_dict.items(): if idx == index: return token # Then check vocabulary for token, idx in self._vocabulary.items(): if idx == index: return token return "[PAD]" def save_vocabulary(self, save_directory: str, filename_prefix: Optional[str] = None) -> Tuple[str]: """Save the vocabulary to a file.""" vocab_file = os.path.join( save_directory, (filename_prefix + "-" if filename_prefix else "") + "vocab.json" ) with open(vocab_file, "w", encoding="utf-8") as f: json.dump(self._vocabulary, f, ensure_ascii=False) return (vocab_file,) def _tokenize_gene_expression(self, x: np.ndarray) -> np.ndarray: """Tokenize gene expression matrix. Args: x: Gene expression matrix (cells x genes) Returns: Tokenized matrix """ # Handle sparse input if issparse(x): x = x.toarray() # Normalize and scale x = np.nan_to_num(x) x = sf_normalize(x) if self.median_counts_per_gene is not None: median_counts = self.median_counts_per_gene.copy() median_counts += median_counts == 0 x = x / median_counts.reshape((1, -1)) # Apply technology mean normalization if available if self.technology_mean is not None and self.technology_mean.shape[0] == x.shape[1]: # Avoid division by zero safe_mean = np.maximum(self.technology_mean, 1e-6) x = x / safe_mean # Apply log1p transformation x = np.log1p(x) # Convert to tokens tokens = _sub_tokenize_data(x, self.max_length, self.aux_tokens) return tokens.astype(np.int32) def __call__(self, data: Union[ad.AnnData, np.ndarray], **kwargs) -> Dict[str, torch.Tensor]: """Tokenize gene expression data. Args: data: AnnData object or numpy array of gene expression data Returns: Dictionary with input_ids and attention_mask tensors """ if isinstance(data, ad.AnnData): adata = data.copy() # Align with reference model if available if hasattr(self, '_load_reference_model'): reference_model = self._load_reference_model() if reference_model is not None: # Store original column types before concatenation original_types = {} for col in ['modality', 'specie', 'assay']: if col in adata.obs.columns: original_types[col] = adata.obs[col].dtype # Concatenate and then remove the reference adata = ad.concat([reference_model, adata], join='outer', axis=0) adata = adata[1:] # Restore original column types after concatenation for col, dtype in original_types.items(): if col in adata.obs.columns: try: adata.obs[col] = adata.obs[col].astype(dtype) except Exception as e: print(f"Warning: Could not convert {col} back to {dtype}: {e}") # Get gene expression data X = adata.X # Get metadata for special tokens modality = adata.obs['modality'] if 'modality' in adata.obs.columns else None species = adata.obs['specie'] if 'specie' in adata.obs.columns else None technology = adata.obs['assay'] if 'assay' in adata.obs.columns else None # Use integer values directly if available if modality is not None: try: if pd.api.types.is_numeric_dtype(modality): modality_tokens = modality.astype(int).tolist() else: modality_tokens = [self.modality_dict.get(m, self._vocabulary["[PAD]"]) for m in modality] except Exception as e: print(f"Warning: Error processing modality tokens: {e}") modality_tokens = [self._vocabulary["[PAD]"]] * len(adata) else: modality_tokens = None if species is not None: try: if pd.api.types.is_numeric_dtype(species): species_tokens = species.astype(int).tolist() else: species_tokens = [self.species_dict.get(s, self._vocabulary["[PAD]"]) for s in species] except Exception as e: print(f"Warning: Error processing species tokens: {e}") species_tokens = [self._vocabulary["[PAD]"]] * len(adata) else: species_tokens = None if technology is not None: try: if pd.api.types.is_numeric_dtype(technology): technology_tokens = technology.astype(int).tolist() else: technology_tokens = [self.technology_dict.get(t, self._vocabulary["[PAD]"]) for t in technology] except Exception as e: print(f"Warning: Error processing technology tokens: {e}") technology_tokens = [self._vocabulary["[PAD]"]] * len(adata) else: technology_tokens = None else: X = data modality_tokens = None species_tokens = None technology_tokens = None # Tokenize gene expression data token_ids = self._tokenize_gene_expression(X) # Add special tokens if available - changed order to [species, technology, modality] special_tokens = np.zeros((token_ids.shape[0], 3), dtype=np.int64) special_token_mask = np.zeros((token_ids.shape[0], 3), dtype=bool) if species_tokens is not None: special_tokens[:, 0] = species_tokens special_token_mask[:, 0] = True if technology_tokens is not None: special_tokens[:, 1] = technology_tokens special_token_mask[:, 1] = True if modality_tokens is not None: special_tokens[:, 2] = modality_tokens special_token_mask[:, 2] = True # Only keep the special tokens that are present (have True in mask) special_tokens = special_tokens[:, special_token_mask[0]] if special_tokens.size > 0: token_ids = np.concatenate([special_tokens, token_ids[:, :(self.max_length - special_tokens.shape[1])]], axis=1) # Create attention mask attention_mask = (token_ids != self._vocabulary["[PAD]"]) return { "input_ids": torch.tensor(token_ids, dtype=torch.long), "attention_mask": torch.tensor(attention_mask) } def get_vocab_size(self) -> int: """Get vocabulary size.""" if self.gene_names is not None: return len(self.gene_names) + self.aux_tokens return max( max(self.modality_dict.values()), max(self.species_dict.values()), max(self.technology_dict.values()) ) + 1 def convert_tokens_to_string(self, tokens: List[str]) -> str: """Convert a sequence of tokens to a string. Not used for gene expression.""" raise NotImplementedError("This tokenizer only works with gene expression data") def build_inputs_with_special_tokens(self, token_ids_0: List[int], token_ids_1: Optional[List[int]] = None) -> List[int]: """Build model inputs from a sequence by adding special tokens.""" # For gene expression data, special tokens are handled in __call__ return token_ids_0 def get_special_tokens_mask(self, token_ids_0: List[int], token_ids_1: Optional[List[int]] = None, already_has_special_tokens: bool = False) -> List[int]: """Get list where entries are [1] if a token is [special] else [0].""" # Consider tokens < aux_tokens as special return [1 if token_id < self.aux_tokens else 0 for token_id in token_ids_0]