"""RegFM loss functions: L_reg with magnitude weighting and hard negative mining.""" import torch import torch.nn.functional as F def compute_reg_loss( R_pred: torch.Tensor, delta_attn: torch.Tensor, valid_mask: torch.Tensor = None, sparse_weight: float = 0.01, ) -> torch.Tensor: """ Regulatory structure supervision loss. Handles: 1. Diagonal exclusion (self-loops not part of GRN) 2. Missing gene masking (genes absent from scGPT vocab) 3. Magnitude-weighted MSE on non-zero entries (strong edges get more gradient) 4. Hard negative mining on zero entries (only penalize top false positives) Args: R_pred: (B, G, G) predicted interaction matrix (already tanh-bounded) delta_attn: (B, G, G) ground truth delta attention (sparse) valid_mask: (G,) bool tensor, True = gene valid in scGPT vocab. None = all valid. sparse_weight: weight for hard negative sparsity loss Returns: loss: scalar tensor """ B, G, _ = R_pred.shape # 1. Exclude diagonal (self-loops) diag_mask = torch.eye(G, dtype=torch.bool, device=R_pred.device) R_pred = R_pred.masked_fill(diag_mask.unsqueeze(0), 0.0) delta_attn = delta_attn.masked_fill(diag_mask.unsqueeze(0), 0.0) # 2. Missing gene masking (zero out rows/columns of invalid genes) if valid_mask is not None: inv = ~valid_mask # inv = True for missing/invalid genes R_pred = R_pred.clone() R_pred[:, inv, :] = 0.0 R_pred[:, :, inv] = 0.0 delta_attn = delta_attn.clone() delta_attn[:, inv, :] = 0.0 delta_attn[:, :, inv] = 0.0 # 3. Non-zero entries: magnitude-weighted MSE mask_nz = delta_attn != 0 n_nonzero = mask_nz.sum().item() if n_nonzero > 0: residual = (R_pred[mask_nz] - delta_attn[mask_nz]).pow(2) mag_weights = delta_attn[mask_nz].abs() mag_weights = mag_weights / mag_weights.sum() loss_nz = (mag_weights * residual).sum() else: loss_nz = R_pred.new_tensor(0.0) # 4. Zero entries: hard negative mining (top-K by |R_pred|) mask_zero = ~mask_nz if valid_mask is not None: valid_2d = valid_mask.unsqueeze(0).unsqueeze(2) & valid_mask.unsqueeze(0).unsqueeze(1) mask_zero = mask_zero & valid_2d # Also exclude diagonal from zero mask mask_zero = mask_zero & ~diag_mask.unsqueeze(0) if mask_zero.any(): zero_preds = R_pred[mask_zero] n_hard = max(min(3 * n_nonzero, len(zero_preds)), 1) _, hard_idx = zero_preds.abs().topk(n_hard) loss_sparse = zero_preds[hard_idx].pow(2).mean() else: loss_sparse = R_pred.new_tensor(0.0) return loss_nz + sparse_weight * loss_sparse def get_lambda_reg(step: int, lambda_reg: float, zero_steps: int, ramp_steps: int) -> float: """Two-phase λ_reg schedule: zero → linear ramp → constant.""" if step < zero_steps: return 0.0 elif step < zero_steps + ramp_steps: return lambda_reg * (step - zero_steps) / ramp_steps else: return lambda_reg