Antigen-Specific Antibody Design via Direct Energy-based Preference Optimization

Antibody design, a crucial task with significant implications across various disciplines such as therapeutics and biology, presents considerable challenges due to its intricate nature. In this paper, we tackle antigen-specific antibody design as a protein sequence-structure co-design problem, considering both rationality and functionality. Leveraging a pre-trained conditional diffusion model that jointly models sequences and structures of complementarity-determining regions (CDR) in antibodies with equivariant neural networks, we propose direct energy-based preference optimization to guide the generation of antibodies with both rational structures and considerable binding affinities to given antigens. Our method involves fine-tuning the pre-trained diffusion model using a residue-level decomposed energy preference. Additionally, we employ gradient surgery to address conflicts between various types of energy, such as attraction and repulsion. Experiments on RAbD benchmark show that our approach effectively optimizes the energy of generated antibodies and achieves state-of-the-art performance in designing high-quality antibodies with low total energy and high binding affinity, demonstrating the superiority of our approach.

Fast Model Debias with Machine Unlearning

Recent discoveries have revealed that deep neural networks might behave in a biased manner in many real-world scenarios. For instance, deep networks trained on a large-scale face recognition dataset CelebA tend to predict blonde hair for females and black hair for males. Such biases not only jeopardize the robustness of models but also perpetuate and amplify social biases, which is especially concerning for automated decision-making processes in healthcare, recruitment, etc., as they could exacerbate unfair economic and social inequalities among different groups. Existing debiasing methods suffer from high costs in bias labeling or model re-training, while also exhibiting a deficiency in terms of elucidating the origins of biases within the model. To this respect, we propose a fast model debiasing framework (FMD) which offers an efficient approach to identify, evaluate and remove biases inherent in trained models. The FMD identifies biased attributes through an explicit counterfactual concept and quantifies the influence of data samples with influence functions. Moreover, we design a machine unlearning-based strategy to efficiently and effectively remove the bias in a trained model with a small counterfactual dataset. Experiments on the Colored MNIST, CelebA, and Adult Income datasets along with experiments with large language models demonstrate that our method achieves superior or competing accuracies compared with state-of-the-art methods while attaining significantly fewer biases and requiring much less debiasing cost. Notably, our method requires only a small external dataset and updating a minimal amount of model parameters, without the requirement of access to training data that may be too large or unavailable in practice.

Towards Distribution-Agnostic Generalized Category Discovery

Data imbalance and open-ended distribution are two intrinsic characteristics of the real visual world. Though encouraging progress has been made in tackling each challenge separately, few works dedicated to combining them towards real-world scenarios. While several previous works have focused on classifying close-set samples and detecting open-set samples during testing, it's still essential to be able to classify unknown subjects as human beings. In this paper, we formally define a more realistic task as distribution-agnostic generalized category discovery (DA-GCD): generating fine-grained predictions for both close- and open-set classes in a long-tailed open-world setting. To tackle the challenging problem, we propose a Self-Balanced Co-Advice contrastive framework (BaCon), which consists of a contrastive-learning branch and a pseudo-labeling branch, working collaboratively to provide interactive supervision to resolve the DA-GCD task. In particular, the contrastive-learning branch provides reliable distribution estimation to regularize the predictions of the pseudo-labeling branch, which in turn guides contrastive learning through self-balanced knowledge transfer and a proposed novel contrastive loss. We compare BaCon with state-of-the-art methods from two closely related fields: imbalanced semi-supervised learning and generalized category discovery. The effectiveness of BaCon is demonstrated with superior performance over all baselines and comprehensive analysis across various datasets. Our code is publicly available.

Robustness-Guided Image Synthesis for Data-Free Quantization

Quantization has emerged as a promising direction for model compression. Recently, data-free quantization has been widely studied as a promising method to avoid privacy concerns, which synthesizes images as an alternative to real training data. Existing methods use classification loss to ensure the reliability of the synthesized images. Unfortunately, even if these images are well-classified by the pre-trained model, they still suffer from low semantics and homogenization issues. Intuitively, these low-semantic images are sensitive to perturbations, and the pre-trained model tends to have inconsistent output when the generator synthesizes an image with poor semantics. To this end, we propose Robustness-Guided Image Synthesis (RIS), a simple but effective method to enrich the semantics of synthetic images and improve image diversity, further boosting the performance of downstream data-free compression tasks. Concretely, we first introduce perturbations on input and model weight, then define the inconsistency metrics at feature and prediction levels before and after perturbations. On the basis of inconsistency on two levels, we design a robustness optimization objective to enhance the semantics of synthetic images. Moreover, we also make our approach diversity-aware by forcing the generator to synthesize images with small correlations in the label space. With RIS, we achieve state-of-the-art performance for various settings on data-free quantization and can be extended to other data-free compression tasks.

AI-enabled Automatic Multimodal Fusion of Cone-Beam CT and Intraoral Scans for Intelligent 3D Tooth-Bone Reconstruction and Clinical Applications

A critical step in virtual dental treatment planning is to accurately delineate all tooth-bone structures from CBCT with high fidelity and accurate anatomical information. Previous studies have established several methods for CBCT segmentation using deep learning. However, the inherent resolution discrepancy of CBCT and the loss of occlusal and dentition information largely limited its clinical applicability. Here, we present a Deep Dental Multimodal Analysis (DDMA) framework consisting of a CBCT segmentation model, an intraoral scan (IOS) segmentation model (the most accurate digital dental model), and a fusion model to generate 3D fused crown-root-bone structures with high fidelity and accurate occlusal and dentition information. Our model was trained with a large-scale dataset with 503 CBCT and 28,559 IOS meshes manually annotated by experienced human experts. For CBCT segmentation, we use a five-fold cross validation test, each with 50 CBCT, and our model achieves an average Dice coefficient and IoU of 93.99% and 88.68%, respectively, significantly outperforming the baselines. For IOS segmentations, our model achieves an mIoU of 93.07% and 95.70% on the maxillary and mandible on a test set of 200 IOS meshes, which are 1.77% and 3.52% higher than the state-of-art method. Our DDMA framework takes about 20 to 25 minutes to generate the fused 3D mesh model following the sequential processing order, compared to over 5 hours by human experts. Notably, our framework has been incorporated into a software by a clear aligner manufacturer, and real-world clinical cases demonstrate that our model can visualize crown-root-bone structures during the entire orthodontic treatment and can predict risks like dehiscence and fenestration. These findings demonstrate the potential of multi-modal deep learning to improve the quality of digital dental models and help dentists make better clinical decisions.