Kyongtae Tyler Bae

Mohamad Koohi-Moghadam, Hongzhe Sun, Hongyan Li et al.

The discovery of anticancer therapeutics has traditionally treated organic small molecules and metal-based coordination complexes as separate chemical domains, limiting knowledge transfer despite their shared biological objectives. This disparity is particularly pronounced in available data, with extensive screening databases for organic compounds compared to only a few thousand characterized metal complexes. Here, we introduce ChemCLIP, a dual-encoder contrastive learning framework that bridges this organic-inorganic divide by learning unified representations based on shared anticancer activities rather than structural similarity. We compiled complementary datasets comprising 44,854 unique organic compounds and 5,164 unique metal complexes, standardized across 60 cancer cell lines. By training parallel encoders with activity-aware hard negative mining, we mapped structurally distinct compounds into a shared 256-dimensional embedding space where biologically similar compounds cluster together regardless of chemical class. We systematically evaluated four molecular encoding strategies: Morgan fingerprints, ChemBERTa, MolFormer, and Chemprop, through quantitative alignment metrics, embedding visualizations, and downstream classification tasks. Morgan fingerprints achieved superior performance with an average alignment ratio of 0.899 and downstream classification AUCs of 0.859 (inorganic) and 0.817 (organic). This work establishes contrastive learning as an effective strategy for unifying disparate chemical domains and provides empirical guidance for encoder selection in multi-modal chemistry applications, with implications extending beyond anticancer drug discovery to any scenario requiring cross-domain chemical knowledge transfer.

Mohamad Koohi-Moghadam, Mohammad-Ali Nikouei Mahani, Kyongtae Tyler Bae

The development of robust artificial intelligence models for histopathology diagnosis is severely constrained by the scarcity of expert-annotated lesion data, particularly for rare pathologies and underrepresented disease subtypes. While data augmentation offers a potential solution, existing methods fail to generate sufficiently realistic lesion morphologies that preserve the complex spatial relationships and cellular architectures characteristic of histopathological tissues. Here we present PathoGen, a diffusion-based generative model that enables controllable, high-fidelity inpainting of lesions into benign histopathology images. Unlike conventional augmentation techniques, PathoGen leverages the iterative refinement process of diffusion models to synthesize lesions with natural tissue boundaries, preserved cellular structures, and authentic staining characteristics. We validate PathoGen across four diverse datasets representing distinct diagnostic challenges: kidney, skin, breast, and prostate pathology. Quantitative assessment confirms that PathoGen outperforms state-of-the-art generative baselines, including conditional GAN and Stable Diffusion, in image fidelity and distributional similarity. Crucially, we show that augmenting training sets with PathoGen-synthesized lesions enhances downstream segmentation performance compared to traditional geometric augmentations, particularly in data-scarce regimes. Besides, by simultaneously generating realistic morphology and pixel-level ground truth, PathoGen effectively overcomes the manual annotation bottleneck. This approach offers a scalable pathway for developing generalizable medical AI systems despite limited expert-labeled data.

Reza Safdari, Mohammad Koohi-Moghaddam, Kyongtae Tyler Bae

In this study, we implemented a two-stage deep learning-based approach to segment lesions in PET/CT images for the AutoPET III challenge. The first stage utilized a DynUNet model for coarse segmentation, identifying broad regions of interest. The second stage refined this segmentation using an ensemble of SwinUNETR, SegResNet, and UNet models. Preprocessing involved resampling images to a common resolution and normalization, while data augmentation techniques such as affine transformations and intensity adjustments were applied to enhance model generalization. The dataset was split into 80% training and 20% validation, excluding healthy cases. This method leverages multi-stage segmentation and model ensembling to achieve precise lesion segmentation, aiming to improve robustness and overall performance.