Computational approaches to drug discovery involve multiple sub-problems, and among them, drug-target binding affinity prediction plays an important role. Despite recent advances, accurately predicting binding affinity remains an open research area. The major objective of our paper is to perform a comprehensive review and comparative analysis of recent machine learning methods for drug-target binding affinity prediction, with a focus on identifying strengths, limitations, and research gaps. We review representative recent deep learning approaches that use common benchmark datasets and evaluation metrics, covering a range of neural network architectures and representation strategies. In addition, we analyze seven widely used benchmark datasets and commonly adopted evaluation metrics for drug-target binding affinity prediction. Our analysis indicates that although many methods report strong performance on standard benchmarks, their effectiveness is often influenced by dataset bias and limited evaluation settings. Furthermore, most methods exhibit reduced performance in cold-start scenarios, highlighting challenges in generalization. We identify several limitations of current approaches, including dataset imbalance, the lack of standardized evaluation, limited real-world applicability, and challenges in cold-start scenarios. We also discuss future research directions, including better dataset design, more robust evaluation methods, improved handling of cold-start problems, and the integration of multimodal representations.
Deep learning for 3D medical image segmentation requires extensive manual annotations, a major bottleneck in volumetric medical imaging. Active learning aims to reduce this burden by selecting informative samples for annotation, but most methods assume that an initial labeled set is already available. This leaves the cold-start problem largely unresolved: how to select the first volumes from a fully unlabeled pool before any task-specific model is trained. We propose CSCS, a Curriculum-Stratified Cold-Start framework that adapts initial sample selection to the structure of the unlabeled dataset. CSCS combines two self-supervised, label-free signals: local typicality, measuring representativeness in the embedding space, and reconstruction-based uncertainty, used as a proxy for sample difficulty. These signals are combined through a weighted geometric score, where the weighting is determined by a closed-form pacing rule based on the effective annotation budget and the Difficulty-Coverage Ratio, a pool-level statistic measuring the alignment between difficulty and representativeness. We evaluate CSCS on four 3D medical image segmentation benchmarks: BraTS, FeTA, Spleen, and an in-house fetal MRI dataset. Using nnU-Net as downstream segmentation model, CSCS shows consistently competitive performance across datasets and annotation budgets, with the strongest gains in low-to-mid annotation regimes. These results suggest that dataset-aware cold-start initialization can improve the robustness of active learning for 3D medical image segmentation by adapting sample selection to the geometry of the unlabeled pool.