Chenghao Liu

Jarrid Rector-Brooks, Théophile Lambert, Marta Skreta et al.

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes without pre-specifying catalytic residues. We introduce DISCO (DIffusion for Sequence-structure CO-design), a multimodal model that co-designs protein sequence and 3D structure around arbitrary biomolecules, as well as inference-time scaling methods that optimize objectives across both modalities. Conditioned solely on reactive intermediates, DISCO designs diverse heme enzymes with novel active-site geometries. These enzymes catalyze new-to-nature carbene-transfer reactions, including alkene cyclopropanation, spirocyclopropanation, B-H, and C(sp$^3$)-H insertions, with high activities exceeding those of engineered enzymes. Random mutagenesis of a selected design further confirmed that enzyme activity can be improved through directed evolution. By providing a scalable route to evolvable enzymes, DISCO broadens the potential scope of genetically encodable transformations. Code is available at https://github.com/DISCO-design/DISCO.

Fengqian Pang, Chunyue Lei, Hongfei Zhao et al.

Drug Mechanism of Action (MoA) mainly investigates how drug molecules interact with cells, which is crucial for drug discovery and clinical application. Recently, deep learning models have been used to recognize MoA by relying on high-content and fluorescence images of cells exposed to various drugs. However, these methods focus on spatial characteristics while overlooking the temporal dynamics of live cells. Time-lapse imaging is more suitable for observing the cell response to drugs. Additionally, drug molecules can trigger cellular dynamic variations related to specific MoA. This indicates that the drug molecule modality may complement the image counterpart. This paper proposes MolCLIP, the first visual language model to combine microscopic cell video- and molecule-modalities. MolCLIP designs a molecule-auxiliary CLIP framework to guide video features in learning the distribution of the molecular latent space. Furthermore, we integrate a metric learning strategy with MolCLIP to optimize the aggregation of video features. Experimental results on the MitoDataset demonstrate that MolCLIP achieves improvements of 51.2% and 20.5% in mAP for drug identification and MoA recognition, respectively.

Xinru Zhang, Chenghao Liu, Ni Ou et al.

Brain lesion segmentation provides a valuable tool for clinical diagnosis, and convolutional neural networks (CNNs) have achieved unprecedented success in the task. Data augmentation is a widely used strategy that improves the training of CNNs, and the design of the augmentation method for brain lesion segmentation is still an open problem. In this work, we propose a simple data augmentation approach, dubbed as CarveMix, for CNN-based brain lesion segmentation. Like other "mix"-based methods, such as Mixup and CutMix, CarveMix stochastically combines two existing labeled images to generate new labeled samples. Yet, unlike these augmentation strategies based on image combination, CarveMix is lesion-aware, where the combination is performed with an attention on the lesions and a proper annotation is created for the generated image. Specifically, from one labeled image we carve a region of interest (ROI) according to the lesion location and geometry, and the size of the ROI is sampled from a probability distribution. The carved ROI then replaces the corresponding voxels in a second labeled image, and the annotation of the second image is replaced accordingly as well. In this way, we generate new labeled images for network training and the lesion information is preserved. To evaluate the proposed method, experiments were performed on two brain lesion datasets. The results show that our method improves the segmentation accuracy compared with other simple data augmentation approaches.