Genetic Programming Algorithm Evolving Robust Unary Costs for Efficient Graph Cut Segmentation

Accurate cell and nuclei segmentation remains challenging due to the sensitivity of classical graph-cut methods to parameter tuning. While deep learning models like U-Net offer strong performance, they require large annotated datasets and substantial GPU resources. This work presents a cost-effective alternative: a genetic programming (GP) framework that jointly optimizes unary cost functions and regularization parameters for graph-cut segmentation, coupled with automatic seed selection. Evaluation is conducted under two distinct protocols: (1) oracle-guided per-image optimization, establishing upper-bound performance (mean Dice 0.822, IoU 0.733), and (2) true generalization via train/test split, where expressions learned on 50 images are applied to 50 unseen images (mean Dice 0.695, IoU 0.588). The fixed-model generalization still significantly outperforms the baseline graph cut (+0.158 Dice, p<0.001). Cross-dataset validation on MoNuSeg (H&E histopathology) achieves a Dice score of 0.823 with the fixed GP model, significantly outperforming the baseline (+0.272). This result uses a single fixed model—the best-performing expression from BBBC038 training—applied in a zero-shot manner to MoNuSeg without any retraining or domain adaptation. All 100 images showed non-negative improvement under oracle optimization in the experiments. The method requires no GPU training, runs in 550 s per image for oracle search, and offers interpretable symbolic cost functions. Code and annotations are provided to ensure reproducibility. This approach offers a practical, interpretable alternative in resource-constrained biomedical imaging settings.