""" Geneformer tokenizer. Input data: Required format: raw counts scRNAseq data without feature selection as .loom file Required row (gene) attribute: "ensembl_id"; Ensembl ID for each gene Required col (cell) attribute: "n_counts"; total read counts in that cell Optional col (cell) attribute: "filter_pass"; binary indicator of whether cell should be tokenized based on user-defined filtering criteria Optional col (cell) attributes: any other cell metadata can be passed on to the tokenized dataset as a custom attribute dictionary as shown below Usage: from geneformer import TranscriptomeTokenizer tk = TranscriptomeTokenizer({"cell_type": "cell_type", "organ_major": "organ_major"}, nproc=4) tk.tokenize_data("data_directory", "output_directory", "output_prefix") """ from __future__ import annotations import logging import pickle import warnings from pathlib import Path from typing import Literal import anndata as ad import loompy as lp import numpy as np import scipy.sparse as sp from datasets import Dataset warnings.filterwarnings("ignore", message=".*The 'nopython' keyword.*") logger = logging.getLogger(__name__) GENE_MEDIAN_FILE = Path(__file__).parent / "gene_median_dictionary.pkl" TOKEN_DICTIONARY_FILE = Path(__file__).parent / "token_dictionary.pkl" def rank_genes(gene_vector, gene_tokens): """ Rank gene expression vector. """ # sort by median-scaled gene values sorted_indices = np.argsort(-gene_vector) return gene_tokens[sorted_indices] def tokenize_cell(gene_vector, gene_tokens): """ Convert normalized gene expression vector to tokenized rank value encoding. """ # create array of gene vector with token indices # mask undetected genes nonzero_mask = np.nonzero(gene_vector)[0] # rank by median-scaled gene values return rank_genes(gene_vector[nonzero_mask], gene_tokens[nonzero_mask]) class TranscriptomeTokenizer: def __init__( self, custom_attr_name_dict=None, nproc=1, chunk_size=512, gene_median_file=GENE_MEDIAN_FILE, token_dictionary_file=TOKEN_DICTIONARY_FILE, ): """ Initialize tokenizer. Parameters ---------- custom_attr_name_dict : None, dict Dictionary of custom attributes to be added to the dataset. Keys are the names of the attributes in the loom file. Values are the names of the attributes in the dataset. nproc : int Number of processes to use for dataset mapping. chunk_size: int = 512 Chunk size for anndata tokenizer. gene_median_file : Path Path to pickle file containing dictionary of non-zero median gene expression values across Genecorpus-30M. token_dictionary_file : Path Path to pickle file containing token dictionary (Ensembl IDs:token). """ # dictionary of custom attributes {output dataset column name: input .loom column name} self.custom_attr_name_dict = custom_attr_name_dict # number of processes for dataset mapping self.nproc = nproc # chunk size for anndata tokenizer self.chunk_size = chunk_size # load dictionary of gene normalization factors # (non-zero median value of expression across Genecorpus-30M) with open(gene_median_file, "rb") as f: self.gene_median_dict = pickle.load(f) # load token dictionary (Ensembl IDs:token) with open(token_dictionary_file, "rb") as f: self.gene_token_dict = pickle.load(f) # gene keys for full vocabulary self.gene_keys = list(self.gene_median_dict.keys()) # protein-coding and miRNA gene list dictionary for selecting .loom rows for tokenization self.genelist_dict = dict(zip(self.gene_keys, [True] * len(self.gene_keys))) def tokenize_data( self, data_directory: Path | str, output_directory: Path | str, output_prefix: str, file_format: Literal["loom", "h5ad"] = "loom", use_generator: bool = False, ): """ Tokenize .loom files in data_directory and save as tokenized .dataset in output_directory. Parameters ---------- data_directory : Path Path to directory containing loom files or anndata files output_directory : Path Path to directory where tokenized data will be saved as .dataset output_prefix : str Prefix for output .dataset file_format : str Format of input files. Can be "loom" or "h5ad". use_generator : bool Whether to use generator or dict for tokenization. """ tokenized_cells, cell_metadata = self.tokenize_files( Path(data_directory), file_format ) tokenized_dataset = self.create_dataset( tokenized_cells, cell_metadata, use_generator=use_generator ) output_path = (Path(output_directory) / output_prefix).with_suffix(".dataset") tokenized_dataset.save_to_disk(output_path) def tokenize_files( self, data_directory, file_format: Literal["loom", "h5ad"] = "loom" ): tokenized_cells = [] if self.custom_attr_name_dict is not None: cell_attr = [attr_key for attr_key in self.custom_attr_name_dict.keys()] cell_metadata = { attr_key: [] for attr_key in self.custom_attr_name_dict.values() } # loops through directories to tokenize .loom files file_found = 0 # loops through directories to tokenize .loom or .h5ad files tokenize_file_fn = ( self.tokenize_loom if file_format == "loom" else self.tokenize_anndata ) for file_path in data_directory.glob("*.{}".format(file_format)): file_found = 1 print(f"Tokenizing {file_path}") file_tokenized_cells, file_cell_metadata = tokenize_file_fn(file_path) tokenized_cells += file_tokenized_cells if self.custom_attr_name_dict is not None: for k in cell_attr: cell_metadata[self.custom_attr_name_dict[k]] += file_cell_metadata[ k ] else: cell_metadata = None if file_found == 0: logger.error( f"No .{file_format} files found in directory {data_directory}." ) raise return tokenized_cells, cell_metadata def tokenize_anndata(self, adata_file_path, target_sum=10_000): adata = ad.read(adata_file_path, backed="r") if self.custom_attr_name_dict is not None: file_cell_metadata = { attr_key: [] for attr_key in self.custom_attr_name_dict.keys() } coding_miRNA_loc = np.where( [self.genelist_dict.get(i, False) for i in adata.var["ensembl_id"]] )[0] norm_factor_vector = np.array( [ self.gene_median_dict[i] for i in adata.var["ensembl_id"][coding_miRNA_loc] ] ) coding_miRNA_ids = adata.var["ensembl_id"][coding_miRNA_loc] coding_miRNA_tokens = np.array( [self.gene_token_dict[i] for i in coding_miRNA_ids] ) try: _ = adata.obs["filter_pass"] except KeyError: var_exists = False else: var_exists = True if var_exists: filter_pass_loc = np.where([i == 1 for i in adata.obs["filter_pass"]])[0] elif not var_exists: print( f"{adata_file_path} has no column attribute 'filter_pass'; tokenizing all cells." ) filter_pass_loc = np.array([i for i in range(adata.shape[0])]) tokenized_cells = [] for i in range(0, len(filter_pass_loc), self.chunk_size): idx = filter_pass_loc[i : i + self.chunk_size] n_counts = adata[idx].obs["n_counts"].values[:, None] X_view = adata[idx, coding_miRNA_loc].X X_norm = X_view / n_counts * target_sum / norm_factor_vector X_norm = sp.csr_matrix(X_norm) tokenized_cells += [ rank_genes(X_norm[i].data, coding_miRNA_tokens[X_norm[i].indices]) for i in range(X_norm.shape[0]) ] # add custom attributes for subview to dict if self.custom_attr_name_dict is not None: for k in file_cell_metadata.keys(): file_cell_metadata[k] += adata[idx].obs[k].tolist() else: file_cell_metadata = None return tokenized_cells, file_cell_metadata def tokenize_loom(self, loom_file_path, target_sum=10_000): if self.custom_attr_name_dict is not None: file_cell_metadata = { attr_key: [] for attr_key in self.custom_attr_name_dict.keys() } with lp.connect(str(loom_file_path)) as data: # define coordinates of detected protein-coding or miRNA genes and vector of their normalization factors coding_miRNA_loc = np.where( [self.genelist_dict.get(i, False) for i in data.ra["ensembl_id"]] )[0] norm_factor_vector = np.array( [ self.gene_median_dict[i] for i in data.ra["ensembl_id"][coding_miRNA_loc] ] ) coding_miRNA_ids = data.ra["ensembl_id"][coding_miRNA_loc] coding_miRNA_tokens = np.array( [self.gene_token_dict[i] for i in coding_miRNA_ids] ) # define coordinates of cells passing filters for inclusion (e.g. QC) try: data.ca["filter_pass"] except AttributeError: var_exists = False else: var_exists = True if var_exists: filter_pass_loc = np.where([i == 1 for i in data.ca["filter_pass"]])[0] elif not var_exists: print( f"{loom_file_path} has no column attribute 'filter_pass'; tokenizing all cells." ) filter_pass_loc = np.array([i for i in range(data.shape[1])]) # scan through .loom files and tokenize cells tokenized_cells = [] for _ix, _selection, view in data.scan(items=filter_pass_loc, axis=1): # select subview with protein-coding and miRNA genes subview = view.view[coding_miRNA_loc, :] # normalize by total counts per cell and multiply by 10,000 to allocate bits to precision # and normalize by gene normalization factors subview_norm_array = ( subview[:, :] / subview.ca.n_counts * target_sum / norm_factor_vector[:, None] ) # tokenize subview gene vectors tokenized_cells += [ tokenize_cell(subview_norm_array[:, i], coding_miRNA_tokens) for i in range(subview_norm_array.shape[1]) ] # add custom attributes for subview to dict if self.custom_attr_name_dict is not None: for k in file_cell_metadata.keys(): file_cell_metadata[k] += subview.ca[k].tolist() else: file_cell_metadata = None return tokenized_cells, file_cell_metadata def create_dataset( self, tokenized_cells, cell_metadata, use_generator=False, keep_uncropped_input_ids=False, ): print("Creating dataset.") # create dict for dataset creation dataset_dict = {"input_ids": tokenized_cells} if self.custom_attr_name_dict is not None: dataset_dict.update(cell_metadata) # create dataset if use_generator: def dict_generator(): for i in range(len(tokenized_cells)): yield {k: dataset_dict[k][i] for k in dataset_dict.keys()} output_dataset = Dataset.from_generator(dict_generator, num_proc=self.nproc) else: output_dataset = Dataset.from_dict(dataset_dict) def format_cell_features(example): # Store original uncropped input_ids in separate feature if keep_uncropped_input_ids: example["input_ids_uncropped"] = example["input_ids"] example["length_uncropped"] = len(example["input_ids"]) # Truncate/Crop input_ids to size 2,048 example["input_ids"] = example["input_ids"][0:2048] example["length"] = len(example["input_ids"]) return example output_dataset_truncated = output_dataset.map( format_cell_features, num_proc=self.nproc ) return output_dataset_truncated