""" 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("loom_data_directory", "output_directory", "output_prefix") """ from __future__ import annotations from typing import Literal import pickle from pathlib import Path import loompy as lp import numpy as np from datasets import Dataset GENE_MEDIAN_FILE = Path(__file__).parent / "gene_median_dictionary.pkl" TOKEN_DICTIONARY_FILE = Path(__file__).parent / "token_dictionary.pkl" 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] # sort by median-scaled gene values sorted_indices = np.argsort(-gene_vector[nonzero_mask]) # tokenize sentence_tokens = gene_tokens[nonzero_mask][sorted_indices] return sentence_tokens class TranscriptomeTokenizer: def __init__( self, custom_attr_name_dict, nproc=1, gene_median_file=GENE_MEDIAN_FILE, token_dictionary_file=TOKEN_DICTIONARY_FILE, ): """ Initialize tokenizer. Parameters ---------- custom_attr_name_dict : 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. 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 # 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", ): """ Tokenize .loom files in loom_data_directory and save as tokenized .dataset in output_directory. Parameters ---------- loom_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". """ tokenized_cells, cell_metadata = self.tokenize_files(Path(data_directory), file_format) tokenized_dataset = self.create_dataset(tokenized_cells, cell_metadata) 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 = [] loom_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 or .h5ad files tokenize_file_fn = self.tokenize_file if file_format == "loom" else self.tokenize_anndata for file_path in data_directory.glob("*.{}".format(file_format)): print(f"Tokenizing {file_path}") file_tokenized_cells, file_cell_metadata = tokenize_file_fn(file_path) tokenized_cells += file_tokenized_cells for k in loom_cell_attr: cell_metadata[self.custom_attr_name_dict[k]] += file_cell_metadata[k] return tokenized_cells, cell_metadata def tokenize_anndata(self, adata_file_path): import anndata as ad adata = ad.read(adata_file_path) 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 AttributeError: var_exists = False else: var_exists = True if var_exists is True: filter_pass_loc = np.where([True if i == 1 else False for i in adata.obs["filter_pass"]])[0] elif var_exists is False: 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[1])]) tokenized_cells = [] adata_filter = adata[:, filter_pass_loc] X_norm = ((adata_filter.X / adata_filter.X.sum(axis=1) * 10_000) / norm_factor_vector).tocsr() tokenized_cells += [ tokenize_cell(X_norm[i, ...].A.flatten(), coding_miRNA_tokens) for i in range(X_norm.shape[0]) ] # add custom attributes for subview to dict for k in file_cell_metadata.keys(): file_cell_metadata[k] += adata_filter.obs[k].tolist() return tokenized_cells, file_cell_metadata def tokenize_file(self, loom_file_path): 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 is True: filter_pass_loc = np.where([True if i == 1 else False for i in data.ca["filter_pass"]])[0] elif var_exists is False: 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 * 10_000 / 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 for k in file_cell_metadata.keys(): file_cell_metadata[k] += subview.ca[k].tolist() return tokenized_cells, file_cell_metadata def create_dataset(self, tokenized_cells, cell_metadata): # create dict for dataset creation dataset_dict = {"input_ids": tokenized_cells} dataset_dict.update(cell_metadata) # create dataset output_dataset = Dataset.from_dict(dataset_dict) # truncate dataset def truncate(example): example["input_ids"] = example["input_ids"][0:2048] return example output_dataset_truncated = output_dataset.map(truncate, num_proc=self.nproc) # measure lengths of dataset def measure_length(example): example["length"] = len(example["input_ids"]) return example output_dataset_truncated_w_length = output_dataset_truncated.map(measure_length, num_proc=self.nproc) return output_dataset_truncated_w_length