Fused Gromov-Wasserstein Contrastive Learning for Effective Enzyme-Reaction Screening

Enzymes are crucial catalysts that enable a wide range of biochemical reactions. Efficiently identifying specific enzymes from vast protein libraries is essential for advancing biocatalysis. Traditional computational methods for enzyme screening and retrieval are time-consuming and resource-intensive. Recently, deep learning approaches have shown promise. However, these methods focus solely on the interaction between enzymes and reactions, overlooking the inherent hierarchical relationships within each domain. To address these limitations, we introduce FGW-CLIP, a novel contrastive learning framework based on optimizing the fused Gromov-Wasserstein distance. FGW-CLIP incorporates multiple alignments, including inter-domain alignment between reactions and enzymes and intra-domain alignment within enzymes and reactions. By introducing a tailored regularization term, our method minimizes the Gromov-Wasserstein distance between enzyme and reaction spaces, which enhances information integration across these domains. Extensive evaluations demonstrate the superiority of FGW-CLIP in challenging enzyme-reaction tasks. On the widely-used EnzymeMap benchmark, FGW-CLIP achieves state-of-the-art performance in enzyme virtual screening, as measured by BEDROC and EF metrics. Moreover, FGW-CLIP consistently outperforms across all three splits of ReactZyme, the largest enzyme-reaction benchmark, demonstrating robust generalization to novel enzymes and reactions. These results position FGW-CLIP as a promising framework for enzyme discovery in complex biochemical settings, with strong adaptability across diverse screening scenarios.

Learning from Simulated and Unsupervised Images through Adversarial Training

With recent progress in graphics, it has become more tractable to train models on synthetic images, potentially avoiding the need for expensive annotations. However, learning from synthetic images may not achieve the desired performance due to a gap between synthetic and real image distributions. To reduce this gap, we propose Simulated+Unsupervised (S+U) learning, where the task is to learn a model to improve the realism of a simulator's output using unlabeled real data, while preserving the annotation information from the simulator. We develop a method for S+U learning that uses an adversarial network similar to Generative Adversarial Networks (GANs), but with synthetic images as inputs instead of random vectors. We make several key modifications to the standard GAN algorithm to preserve annotations, avoid artifacts, and stabilize training: (i) a 'self-regularization' term, (ii) a local adversarial loss, and (iii) updating the discriminator using a history of refined images. We show that this enables generation of highly realistic images, which we demonstrate both qualitatively and with a user study. We quantitatively evaluate the generated images by training models for gaze estimation and hand pose estimation. We show a significant improvement over using synthetic images, and achieve state-of-the-art results on the MPIIGaze dataset without any labeled real data.