import os import torch from torch import nn from torch.utils.data import Dataset, DataLoader import time import traceback import numpy as np from anndata import AnnData import scanpy as sc from typing import List, Tuple, Dict, Optional from scgpt.tokenizer import tokenize_and_pad_batch, random_mask_value from scgpt import SubsetsBatchSampler from scgpt.loss import ( masked_relative_error, criterion_neg_log_bernoulli, ) from scgpt.utils import eval_scib_metrics import warnings from scipy.sparse import issparse from sklearn.metrics import accuracy_score, precision_score, recall_score, f1_score def prepare_data( tokenized_train, tokenized_valid, train_batch_labels, valid_batch_labels, config, epoch, train_celltype_labels=None, valid_celltype_labels=None, sort_seq_batch=False, ) -> Tuple[Dict[str, torch.Tensor]]: assert config.task in ["annotation", "integration", "perturb", "multiomic"] masked_values_train = random_mask_value( tokenized_train["values"], mask_ratio=config.mask_ratio, mask_value=config.mask_value, pad_value=config.pad_value, ) masked_values_valid = random_mask_value( tokenized_valid["values"], mask_ratio=config.mask_ratio, mask_value=config.mask_value, pad_value=config.pad_value, ) print( f"random masking at epoch {epoch:3d}, ratio of masked values in train: ", f"{(masked_values_train == config.mask_value).sum() / (masked_values_train - config.pad_value).count_nonzero():.4f}", ) input_gene_ids_train, input_gene_ids_valid = ( tokenized_train["genes"], tokenized_valid["genes"], ) input_values_train, input_values_valid = masked_values_train, masked_values_valid target_values_train, target_values_valid = ( tokenized_train["values"], tokenized_valid["values"], ) tensor_batch_labels_train = torch.from_numpy(train_batch_labels).long() tensor_batch_labels_valid = torch.from_numpy(valid_batch_labels).long() if config.task == "annotation": tensor_celltype_labels_train = torch.from_numpy(train_celltype_labels).long() tensor_celltype_labels_valid = torch.from_numpy(valid_celltype_labels).long() if config.task == "multiomic": tensor_mod_types_train, tensor_mod_types_valid = ( tokenized_train["mod_types"].long(), tokenized_valid["mod_types"].long(), ) if sort_seq_batch: train_sort_ids = np.argsort(train_batch_labels) input_gene_ids_train = input_gene_ids_train[train_sort_ids] input_values_train = input_values_train[train_sort_ids] target_values_train = target_values_train[train_sort_ids] tensor_batch_labels_train = tensor_batch_labels_train[train_sort_ids] if config.task == "annotation": tensor_celltype_labels_train = tensor_celltype_labels_train[train_sort_ids] if config.task == "multiomic": tensor_mod_types_train = tensor_mod_types_train[train_sort_ids] valid_sort_ids = np.argsort(valid_batch_labels) input_gene_ids_valid = input_gene_ids_valid[valid_sort_ids] input_values_valid = input_values_valid[valid_sort_ids] target_values_valid = target_values_valid[valid_sort_ids] tensor_batch_labels_valid = tensor_batch_labels_valid[valid_sort_ids] if config.task == "annotation": tensor_celltype_labels_valid = tensor_celltype_labels_valid[valid_sort_ids] if config.task == "multiomic": tensor_mod_types_valid = tensor_mod_types_valid[valid_sort_ids] train_data_pt = { "gene_ids": input_gene_ids_train, "values": input_values_train, "target_values": target_values_train, "batch_labels": tensor_batch_labels_train, } valid_data_pt = { "gene_ids": input_gene_ids_valid, "values": input_values_valid, "target_values": target_values_valid, "batch_labels": tensor_batch_labels_valid, } if config.task == "annotation": train_data_pt["celltype_labels"] = tensor_celltype_labels_train valid_data_pt["celltype_labels"] = tensor_celltype_labels_valid if config.task == "multiomic": train_data_pt["mod_types"] = tensor_mod_types_train valid_data_pt["mod_types"] = tensor_mod_types_valid return train_data_pt, valid_data_pt class SeqDataset(Dataset): def __init__(self, data: Dict[str, torch.Tensor]): self.data = data def __len__(self): return self.data["gene_ids"].shape[0] def __getitem__(self, idx): return {k: v[idx] for k, v in self.data.items()} # data_loader def prepare_dataloader( data_pt: Dict[str, torch.Tensor], batch_size: int, shuffle: bool = False, intra_domain_shuffle: bool = False, drop_last: bool = False, num_workers: int = 0, per_seq_batch_sample: bool = False, ) -> DataLoader: dataset = SeqDataset(data_pt) if per_seq_batch_sample: # find the indices of samples in each seq batch subsets = [] batch_labels_array = data_pt["batch_labels"].numpy() for batch_label in np.unique(batch_labels_array): batch_indices = np.where(batch_labels_array == batch_label)[0].tolist() subsets.append(batch_indices) data_loader = DataLoader( dataset=dataset, batch_sampler=SubsetsBatchSampler( subsets, batch_size, intra_subset_shuffle=intra_domain_shuffle, inter_subset_shuffle=shuffle, drop_last=drop_last, ), num_workers=num_workers, pin_memory=True, ) return data_loader data_loader = DataLoader( dataset=dataset, batch_size=batch_size, shuffle=shuffle, drop_last=drop_last, num_workers=num_workers, pin_memory=True, ) return data_loader def train( model: nn.Module, loader: DataLoader, vocab, criterion_gep_gepc, criterion_dab, criterion_cls, scaler, optimizer, scheduler, device, config, logger, epoch, ) -> None: """ Train the model for one epoch. """ import wandb model.train() total_loss, total_gep, total_cls, total_gepc, total_ecs, total_dab = ( 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, ) total_zero_log_prob, total_gepc_zero_log_prob = 0.0, 0.0 # total_error = 0.0 log_interval = config.log_interval start_time = time.time() num_batches = len(loader) for batch, batch_data in enumerate(loader): input_gene_ids = batch_data["gene_ids"].to(device) input_values = batch_data["values"].to(device) target_values = batch_data["target_values"].to(device) batch_labels = batch_data["batch_labels"].to(device) if config.task == "annotation": celltype_labels = batch_data["celltype_labels"].to(device) if config.task == "multiomic": mod_types = batch_data["mod_types"].to(device) src_key_padding_mask = input_gene_ids.eq(vocab[config.pad_token]) with torch.cuda.amp.autocast(enabled=config.amp): output_dict = model( input_gene_ids, input_values, src_key_padding_mask=src_key_padding_mask, batch_labels=batch_labels if config.use_batch_labels or config.DSBN else None, CLS=config.CLS, MVC=config.GEPC, ECS=config.ESC, mod_types=mod_types if config.use_mod else None, # do_sample=do_sample_in_train, # generative_training=False ) masked_positions = input_values.eq( config.mask_value ) # the postions to predict loss = 0.0 metrics_to_log = {} if config.GEP: loss_gep = criterion_gep_gepc( output_dict["mlm_output"], target_values, masked_positions ) loss = loss + loss_gep metrics_to_log = {"train/gep": loss_gep.item()} if config.GEP and config.explicit_zero_prob: loss_zero_log_prob = criterion_neg_log_bernoulli( output_dict["mlm_zero_probs"], target_values, masked_positions ) loss = loss + loss_zero_log_prob metrics_to_log.update({"train/nzlp": loss_zero_log_prob.item()}) if config.GEPC: loss_gepc = criterion_gep_gepc( output_dict["mvc_output"], target_values, masked_positions ) loss = loss + loss_gepc metrics_to_log.update({"train/mvc": loss_gepc.item()}) if config.GEPC and config.explicit_zero_prob: loss_gepc_zero_log_prob = criterion_neg_log_bernoulli( output_dict["mvc_zero_probs"], target_values, masked_positions ) loss = loss + loss_gepc_zero_log_prob metrics_to_log.update( {"train/mvc_nzlp": loss_gepc_zero_log_prob.item()} ) if config.CLS: loss_cls = criterion_cls(output_dict["cls_output"], celltype_labels) loss = loss + loss_cls metrics_to_log.update({"train/cls": loss_cls.item()}) error_rate = 1 - ( (output_dict["cls_output"].argmax(1) == celltype_labels) .sum() .item() ) / celltype_labels.size(0) if config.ESC: loss_ecs = 10 * output_dict["loss_ecs"] loss = loss + loss_ecs metrics_to_log.update({"train/ecs": loss_ecs.item()}) if config.DAR: # try weighting and separate optimizer loss_dab = criterion_dab(output_dict["dab_output"], batch_labels) loss = loss + config.dab_weight * loss_dab metrics_to_log.update({"train/dab": loss_dab.item()}) model.zero_grad() scaler.scale(loss).backward() scaler.unscale_(optimizer) with warnings.catch_warnings(record=True) as w: warnings.filterwarnings("always") torch.nn.utils.clip_grad_norm_( model.parameters(), 1.0, error_if_nonfinite=False if scaler.is_enabled() else True, ) if len(w) > 0: logger.warning( f"Found infinite gradient. This may be caused by the gradient " f"scaler. The current scale is {scaler.get_scale()}. This warning " "can be ignored if no longer occurs after autoscaling of the scaler." ) scaler.step(optimizer) scaler.update() wandb.log(metrics_to_log) total_loss += loss.item() total_gep += loss_gep.item() if config.GEP else 0.0 total_cls += loss_cls.item() if config.CLS else 0.0 total_gepc += loss_gepc.item() if config.GEPC else 0.0 total_ecs += loss_ecs.item() if config.ESC else 0.0 total_dab += loss_dab.item() if config.DAR else 0.0 total_zero_log_prob += ( loss_zero_log_prob.item() if config.GEP and config.explicit_zero_prob else 0.0 ) total_gepc_zero_log_prob += ( loss_gepc_zero_log_prob.item() if config.GEPC and config.explicit_zero_prob else 0.0 ) if batch % log_interval == 0 and batch > 0: lr = scheduler.get_last_lr()[0] ms_per_batch = (time.time() - start_time) * 1000 / log_interval cur_loss = total_loss / log_interval cur_gep = total_gep / log_interval if config.GEP else 0.0 cur_cls = total_cls / log_interval if config.CLS else 0.0 cur_gepc = total_gepc / log_interval if config.GEPC else 0.0 cur_ecs = total_ecs / log_interval if config.ESC else 0.0 cur_dab = total_dab / log_interval if config.DAR else 0.0 cur_zero_log_prob = ( total_zero_log_prob / log_interval if config.explicit_zero_prob else 0.0 ) cur_gepc_zero_log_prob = ( total_gepc_zero_log_prob / log_interval if config.GEPC and config.explicit_zero_prob else 0.0 ) # cur_error = total_error / log_interval logger.info( f"| epoch {epoch:3d} | {batch:3d}/{num_batches:3d} batches | " f"lr {lr:05.5f} | ms/batch {ms_per_batch:5.2f} | " f"loss {cur_loss:5.2f} | " + (f"gep {cur_gep:5.2f} |" if config.GEP else "") + (f"cls {cur_cls:5.2f} | " if config.CLS else "") # + (f"err {cur_error:5.2f} | " if config.CLS else "") + (f"gepc {cur_gepc:5.2f} |" if config.GEPC else "") + (f"ecs {cur_ecs:5.2f} |" if config.ESC else "") + (f"dar {cur_dab:5.2f} |" if config.DAR else "") ) total_loss = 0 total_gep = 0 total_cls = 0 total_gepc = 0 total_ecs = 0 total_dab = 0 total_zero_log_prob = 0 total_gepc_zero_log_prob = 0 # total_error = 0 start_time = time.time() def define_wandb_metrcis(): import wandb wandb.define_metric("valid/loss", summary="min", step_metric="epoch") wandb.define_metric("test/avg_bio", summary="max") def evaluate( model: nn.Module, loader: DataLoader, vocab, criterion_gep_gepc, criterion_dab, criterion_cls, device, config, epoch, ) -> float: """ Evaluate the model on the evaluation data. """ import wandb model.eval() total_loss = 0.0 # total_error = 0.0 total_dab = 0.0 total_num = 0 with torch.no_grad(): for batch_data in loader: input_gene_ids = batch_data["gene_ids"].to(device) input_values = batch_data["values"].to(device) target_values = batch_data["target_values"].to(device) batch_labels = batch_data["batch_labels"].to(device) if config.task == "annotation": celltype_labels = batch_data["celltype_labels"].to(device) if config.task == "multiomic": mod_types = batch_data["mod_types"].to(device) src_key_padding_mask = input_gene_ids.eq(vocab[config.pad_token]) with torch.cuda.amp.autocast(enabled=config.amp): output_dict = model( input_gene_ids, input_values, src_key_padding_mask=src_key_padding_mask, batch_labels=batch_labels if config.use_batch_labels or config.DSBN else None, CLS=config.CLS, # evaluation does not need CLS or CCE MVC=False, ECS=False, mod_types=mod_types if config.use_mod else None, # do_sample=do_sample_in_train, # generative_training = False, ) if config.task == "annotation": output_values = output_dict["cls_output"] loss = criterion_cls(output_values, celltype_labels) elif config.task in ["integration", "multiomic"]: output_values = output_dict["mlm_output"] masked_positions = input_values.eq(config.mask_value) loss = criterion_gep_gepc( output_values, target_values, masked_positions ) if config.DAR: loss_dab = criterion_dab(output_dict["dab_output"], batch_labels) total_loss += loss.item() * len(input_gene_ids) if config.DAR: total_dab += ( loss_dab.item() * len(input_gene_ids) if config.DAR else 0.0 ) else: total_dab = 0 total_num += len(input_gene_ids) wandb.log( { "valid/loss": (total_loss + config.dab_weight * total_dab) / total_num, "epoch": epoch, }, ) return total_loss / total_num def predict( model: nn.Module, loader: DataLoader, vocab, config, device, ) -> float: """ Evaluate the model on the evaluation data. """ model.eval() predictions = [] with torch.no_grad(): for batch_data in loader: input_gene_ids = batch_data["gene_ids"].to(device) input_values = batch_data["values"].to(device) target_values = batch_data["target_values"].to(device) batch_labels = batch_data["batch_labels"].to(device) celltype_labels = batch_data["celltype_labels"].to(device) src_key_padding_mask = input_gene_ids.eq(vocab[config.pad_token]) with torch.cuda.amp.autocast(enabled=config.amp): output_dict = model( input_gene_ids, input_values, src_key_padding_mask=src_key_padding_mask, batch_labels=batch_labels if config.use_batch_labels or config.DSBN else None, CLS=config.CLS, MVC=config.GEPC, ECS=config.ESC, ) output_values = output_dict["cls_output"] preds = output_values.argmax(1).cpu().numpy() predictions.append(preds) return np.concatenate(predictions, axis=0) # %% inference def test( model: nn.Module, adata: DataLoader, gene_ids, vocab, config, device, logger ) -> float: all_counts = ( adata.layers[config.input_layer_key].toarray() if issparse(adata.layers[config.input_layer_key]) else adata.layers[config.input_layer_key] ) celltypes_labels = adata.obs["celltype_id"].tolist() # make sure count from 0 celltypes_labels = np.array(celltypes_labels) batch_ids = adata.obs["batch_id"].tolist() batch_ids = np.array(batch_ids) tokenized_test = tokenize_and_pad_batch( all_counts, gene_ids, max_len=config.max_seq_len, vocab=vocab, pad_token=config.pad_token, pad_value=config.pad_value, append_cls=True, # append token at the beginning include_zero_gene=config.include_zero_gene, ) input_values_test = random_mask_value( tokenized_test["values"], mask_ratio=config.mask_ratio, mask_value=config.mask_value, pad_value=config.pad_value, ) test_data_pt = { "gene_ids": tokenized_test["genes"], "values": input_values_test, "target_values": tokenized_test["values"], "batch_labels": torch.from_numpy(batch_ids).long(), "celltype_labels": torch.from_numpy(celltypes_labels).long(), } test_loader = DataLoader( dataset=SeqDataset(test_data_pt), batch_size=config.batch_size, shuffle=False, drop_last=False, num_workers=min(len(os.sched_getaffinity(0)), config.batch_size // 2), pin_memory=True, ) model.eval() predictions = predict( model, test_loader, vocab, config, device, ) # compute accuracy, precision, recall, f1 accuracy = accuracy_score(celltypes_labels, predictions) precision = precision_score(celltypes_labels, predictions, average="macro") recall = recall_score(celltypes_labels, predictions, average="macro") macro_f1 = f1_score(celltypes_labels, predictions, average="macro") micro_f1 = f1_score(celltypes_labels, predictions, average="micro") logger.info( f"Accuracy: {accuracy:.3f}, Precision: {precision:.3f}, Recall: {recall:.3f}, " f"Macro F1: {macro_f1:.3f}, Micro F1: {micro_f1:.3f}" ) results = { "test/accuracy": accuracy, "test/precision": precision, "test/recall": recall, "test/macro_f1": macro_f1, "test/micro_f1": micro_f1, } return predictions, celltypes_labels, results def eval_testdata( model: nn.Module, adata_t: AnnData, gene_ids, vocab, config, logger, include_types: List[str] = ["cls"], ) -> Optional[Dict]: """evaluate the model on test dataset of adata_t""" model.eval() # copy adata_t to avoid reuse previously computed results stored in adata_t adata_t = adata_t.copy() all_counts = ( adata_t.layers[config.input_layer_key].toarray() if issparse(adata_t.layers[config.input_layer_key]) else adata_t.layers[config.input_layer_key] ) celltypes_labels = adata_t.obs["celltype"].tolist() celltypes_labels = np.array(celltypes_labels) batch_ids = adata_t.obs["batch_id"].tolist() batch_ids = np.array(batch_ids) # Evaluate cls cell embeddings if "cls" in include_types: logger.info("Evaluating cls cell embeddings") tokenized_all = tokenize_and_pad_batch( all_counts, gene_ids, max_len=config.max_seq_len, vocab=vocab, pad_token=config.pad_token, pad_value=config.pad_value, append_cls=True, # append token at the beginning include_zero_gene=config.include_zero_gene, ) all_gene_ids, all_values = tokenized_all["genes"], tokenized_all["values"] src_key_padding_mask = all_gene_ids.eq(vocab[config.pad_token]) with torch.no_grad(), torch.cuda.amp.autocast(enabled=config.amp): cell_embeddings = model.encode_batch( all_gene_ids, all_values.float(), src_key_padding_mask=src_key_padding_mask, batch_size=config.batch_size, batch_labels=torch.from_numpy(batch_ids).long() if config.DSBN or config.DAR or config.use_batch_labels else None, time_step=0, return_np=True, ) cell_embeddings = cell_embeddings / np.linalg.norm( cell_embeddings, axis=1, keepdims=True ) adata_t.obsm["X_scGPT"] = cell_embeddings results = {} try: results = eval_scib_metrics(adata_t) except Exception as e: traceback.print_exc() logger.error(e) sc.pp.neighbors(adata_t, use_rep="X_scGPT") sc.tl.umap(adata_t, min_dist=0.3) fig = sc.pl.umap( adata_t, color=["str_batch"], title=[f"batch, avg_bio = {results.get('avg_bio', 0.0):.4f}"], frameon=False, return_fig=True, show=False, ) results["batch_umap"] = fig sc.pp.neighbors(adata_t, use_rep="X_scGPT") sc.tl.umap(adata_t, min_dist=0.3) fig = sc.pl.umap( adata_t, color=["celltype"], title=[ f"celltype, avg_bio = {results.get('avg_bio', 0.0):.4f}", ], frameon=False, return_fig=True, show=False, ) results["celltype_umap"] = fig if len(include_types) == 1: return results