""" RegFMDenoiser: single-flow training and inference for RegFM. No cascaded time steps, no latent ODE — just scDFM flow + L_reg. """ import torch import torch.nn.functional as F import torchdiffeq from src._scdfm_imports import AffineProbPath, CondOTScheduler, make_lognorm_poisson_noise from src.loss import compute_reg_loss, get_lambda_reg class RegFMDenoiser: """Handles train_step and generation for RegFM.""" def __init__(self, model, config, valid_mask=None): """ Args: model: RegFMModel instance config: RegFMConfig valid_mask: (G_full,) bool tensor — True = gene valid in scGPT vocab """ self.model = model self.config = config self.path = AffineProbPath(scheduler=CondOTScheduler()) self.valid_mask_full = valid_mask def _sample_time(self, B, device): """Sample timesteps using logit-normal or uniform.""" if self.config.t_sample_mode == "logit_normal": u = torch.randn(B, device=device) * self.config.t_std + self.config.t_mean t = torch.sigmoid(u) else: t = torch.rand(B, device=device) return t.clamp(1e-5, 1.0 - 1e-5) def train_step(self, batch, step, gene_ids, accelerator): """ One training step of RegFM. Args: batch: dict from GRNDatasetWrapper with keys: src_cell_data (B, G_sub), tgt_cell_data (B, G_sub), condition_id (B, 2), z_target (B, G_sub, G_sub), gene_ids_sub (G_sub,), input_gene_ids (G_sub,) step: current training iteration (for λ_reg schedule) gene_ids: full gene_ids tensor (G_full,) on device accelerator: HuggingFace Accelerator Returns: dict with loss, loss_vel, loss_reg, loss_mmd, lambda_reg_eff """ device = accelerator.device cfg = self.config source = batch["src_cell_data"].to(device) target = batch["tgt_cell_data"].to(device) delta_attn = batch["z_target"].to(device) gene_ids_sub = batch["gene_ids_sub"].to(device) input_gene_ids = batch["input_gene_ids"] perturbation_id = batch["condition_id"].to(device) B = source.shape[0] # --- Flow matching path --- t = self._sample_time(B, device) if cfg.noise_type == "Gaussian": noise = torch.randn_like(target) else: noise = make_lognorm_poisson_noise( target_log=source, alpha=cfg.poisson_alpha, per_cell_L=cfg.poisson_target_sum if cfg.poisson_target_sum > 0 else 1e4, ) path_sample = self.path.sample(t=t, x_0=noise, x_1=target) x_t = path_sample.x_t v_target = path_sample.dx_t # --- Forward --- gene_input = gene_ids_sub.unsqueeze(0).expand(B, -1) v_pred, R_pred = self.model( gene_input, x_t, t, source, perturbation_id=perturbation_id, gene_id_all=gene_input, mode="predict_y", ) # --- L_vel --- loss_vel = F.mse_loss(v_pred, v_target) # --- L_reg --- valid_sub = None if self.valid_mask_full is not None: valid_sub = self.valid_mask_full[input_gene_ids.cpu()].to(device) loss_reg = compute_reg_loss( R_pred, delta_attn, valid_mask=valid_sub, sparse_weight=cfg.sparse_reg_weight, ) lambda_eff = get_lambda_reg( step, cfg.lambda_reg, cfg.lambda_reg_zero_steps, cfg.lambda_reg_ramp_steps ) # --- L_mmd (optional) --- loss_mmd = torch.tensor(0.0, device=device) if cfg.use_mmd_loss and cfg.gamma > 0: x1_hat = x_t + v_pred * (1.0 - t).unsqueeze(-1) loss_mmd = self._mmd_loss(x1_hat, target) # --- Total --- loss = loss_vel + lambda_eff * loss_reg + cfg.gamma * loss_mmd return { "loss": loss, "loss_vel": loss_vel.item(), "loss_reg": loss_reg.item(), "loss_mmd": loss_mmd.item(), "lambda_reg_eff": lambda_eff, } @staticmethod def _mmd_loss(x_pred, x_target): """Multi-scale MMD loss (same as scDFM).""" from scdfm_src.loss.metrics import median_sigmas, mmd2_unbiased_multi_sigma sigmas = median_sigmas(x_target, scales=(0.5, 1.0, 2.0, 4.0)) return mmd2_unbiased_multi_sigma(x_pred, x_target, sigmas) @torch.no_grad() def generate(self, source, perturbation_id, gene_ids_sub, steps=None, method=None): """ Generate expression predictions via single-stage ODE. Args: source: (B, G_sub) control expression perturbation_id: (B, 2) perturbation IDs gene_ids_sub: (G_sub,) vocab-encoded gene IDs steps: ODE integration steps (default: config.ode_steps) method: ODE method (default: config.ode_method) Returns: x_pred: (B, G_sub) predicted expression, clamped >= 0 """ cfg = self.config steps = steps or cfg.ode_steps method = method or cfg.ode_method device = source.device B = source.shape[0] if cfg.noise_type == "Gaussian": x_init = torch.randn_like(source) else: x_init = make_lognorm_poisson_noise( target_log=source, alpha=cfg.poisson_alpha, per_cell_L=cfg.poisson_target_sum if cfg.poisson_target_sum > 0 else 1e4, ) gene_input = gene_ids_sub.unsqueeze(0).expand(B, -1) def ode_fn(t_scalar, x): t_batch = t_scalar.expand(B).to(device) v, _R = self.model( gene_input, x, t_batch, source, perturbation_id=perturbation_id, gene_id_all=gene_input, mode="predict_y", ) return v traj = torchdiffeq.odeint( ode_fn, x_init, torch.linspace(0, 1, steps, device=device), method=method, atol=1e-4, rtol=1e-4, ) return torch.clamp(traj[-1], min=0)