Multimodal Large Language Models (MLLMs) have shown impressive performance in vision and text tasks. However, hallucination remains a major challenge, especially in fields like healthcare where details are critical. In this work, we show how MLLMs may be enhanced to support Visual RAG (V-RAG), a retrieval-augmented generation framework that incorporates both text and visual data from retrieved images. On the MIMIC-CXR chest X-ray report generation and Multicare medical image caption generation datasets, we show that Visual RAG improves the accuracy of entity probing, which asks whether a medical entities is grounded by an image. We show that the improvements extend both to frequent and rare entities, the latter of which may have less positive training data. Downstream, we apply V-RAG with entity probing to correct hallucinations and generate more clinically accurate X-ray reports, obtaining a higher RadGraph-F1 score.

We consider the conditional generation of 3D drug-like molecules with \textit{explicit control} over molecular properties such as drug-like properties (e.g., Quantitative Estimate of Druglikeness or Synthetic Accessibility score) and effectively binding to specific protein sites. To tackle this problem, we propose an E(3)-equivariant Wasserstein autoencoder and factorize the latent space of our generative model into two disentangled aspects: molecular properties and the remaining structural context of 3D molecules. Our model ensures explicit control over these molecular attributes while maintaining equivariance of coordinate representation and invariance of data likelihood. Furthermore, we introduce a novel alignment-based coordinate loss to adapt equivariant networks for auto-regressive de-novo 3D molecule generation from scratch. Extensive experiments validate our model's effectiveness on property-guided and context-guided molecule generation, both for de-novo 3D molecule design and structure-based drug discovery against protein targets.

When performing complex multi-step reasoning tasks, the ability of Large Language Models (LLMs) to derive structured intermediate proof steps is important for ensuring that the models truly perform the desired reasoning and for improving models' explainability. This paper is centred around a focused study: whether the current state-of-the-art generalist LLMs can leverage the structures in a few examples to better construct the proof structures with \textit{in-context learning}. Our study specifically focuses on structure-aware demonstration and structure-aware pruning. We demonstrate that they both help improve performance. A detailed analysis is provided to help understand the results.

Discrete diffusion models have achieved success in tasks like image generation and masked language modeling but face limitations in controlled content editing. We introduce DICE (Discrete Inversion for Controllable Editing), the first approach to enable precise inversion for discrete diffusion models, including multinomial diffusion and masked generative models. By recording noise sequences and masking patterns during the reverse diffusion process, DICE enables accurate reconstruction and flexible editing of discrete data without the need for predefined masks or attention manipulation. We demonstrate the effectiveness of DICE across both image and text domains, evaluating it on models such as VQ-Diffusion, Paella, and RoBERTa. Our results show that DICE preserves high data fidelity while enhancing editing capabilities, offering new opportunities for fine-grained content manipulation in discrete spaces. For project webpage, see https://hexiaoxiao-cs.github.io/DICE/.

T cells monitor the health status of cells by identifying foreign peptides displayed on their surface. T-cell receptors (TCRs), which are protein complexes found on the surface of T cells, are able to bind to these peptides. This process is known as TCR recognition and constitutes a key step for immune response. Optimizing TCR sequences for TCR recognition represents a fundamental step towards the development of personalized treatments to trigger immune responses killing cancerous or virus-infected cells. In this paper, we formulated the search for these optimized TCRs as a reinforcement learning (RL) problem, and presented a framework TCRPPO with a mutation policy using proximal policy optimization. TCRPPO mutates TCRs into effective ones that can recognize given peptides. TCRPPO leverages a reward function that combines the likelihoods of mutated sequences being valid TCRs measured by a new scoring function based on deep autoencoders, with the probabilities of mutated sequences recognizing peptides from a peptide-TCR interaction predictor. We compared TCRPPO with multiple baseline methods and demonstrated that TCRPPO significantly outperforms all the baseline methods to generate positive binding and valid TCRs. These results demonstrate the potential of TCRPPO for both precision immunotherapy and peptide-recognizing TCR motif discovery.

Learning disentangled representations leads to interpretable models and facilitates data generation with style transfer, which has been extensively studied on static data such as images in an unsupervised learning framework. However, only a few works have explored unsupervised disentangled sequential representation learning due to challenges of generating sequential data. In this paper, we propose recurrent Wasserstein Autoencoder (R-WAE), a new framework for generative modeling of sequential data. Our theoretical analysis shows that, R-WAE minimizes an upper bound of a penalized form of the Wasserstein distance between model distribution and sequential data distribution, and simultaneously maximizes the mutual information between input data and different disentangled latent factors, respectively. This is superior to (recurrent) VAE which does not explicitly enforce mutual information maximization between input data and disentangled latent representations. When the number of actions in sequential data is available as weak supervision information, R-WAE is extended to learn a categorical latent representation of actions to improve its disentanglement. Experiments on a variety of datasets show that our models outperform other baselines with the same settings in terms of disentanglement and unconditional video generation both quantitatively and qualitatively. Unsupervised representation learning is an important research topic in machine learning.

In drug discovery, molecule optimization is an important step in order to modify drug candidates into better ones in terms of desired drug properties. With the recent advance of Artificial Intelligence, this traditionally in vitro process has been increasingly facilitated by in silico approaches. We present an innovative in silico approach to computationally optimizing molecules and formulate the problem as to generate optimized molecular graphs via deep generative models. Our generative models follow the key idea of fragment-based drug design, and optimize molecules by modifying their small fragments. Our models learn how to identify the to-be-optimized fragments and how to modify such fragments by learning from the difference of molecules that have good and bad properties. In optimizing a new molecule, our models apply the learned signals to decode optimized fragments at the predicted location of the fragments. We also construct multiple such models into a pipeline such that each of the models in the pipeline is able to optimize one fragment, and thus the entire pipeline is able to modify multiple fragments of molecule if needed. We compare our models with other state-of-the-art methods on benchmark datasets and demonstrate that our methods significantly outperform others with more than 80% property improvement under moderate molecular similarity constraints, and more than 10% property improvement under high molecular similarity constraints.

T-cell receptors can recognize foreign peptides bound to major histocompatibility complex (MHC) class-I proteins, and thus trigger the adaptive immune response. Therefore, identifying peptides that can bind to MHC class-I molecules plays a vital role in the design of peptide vaccines. Many computational methods, for example, the state-of-the-art allele-specific method MHCflurry, have been developed to predict the binding affinities between peptides and MHC molecules. In this manuscript, we develop two allele-specific Convolutional Neural Network (CNN)-based methods named ConvM and SpConvM to tackle the binding prediction problem. Specifically, we formulate the problem as to optimize the rankings of peptide-MHC bindings via ranking-based learning objectives. Such optimization is more robust and tolerant to the measurement inaccuracy of binding affinities, and therefore enables more accurate prioritization of binding peptides. In addition, we develop a new position encoding method in ConvM and SpConvM to better identify the most important amino acids for the binding events. Our experimental results demonstrate that our models significantly outperform the state-of-the-art methods including MHCflurry with an average percentage improvement of 6.70% on AUC and 17.10% on ROC5 across 128 alleles.

Learning disentangled representations of natural language is essential for many NLP tasks, e.g., conditional text generation, style transfer, personalized dialogue systems, etc. Similar problems have been studied extensively for other forms of data, such as images and videos. However, the discrete nature of natural language makes the disentangling of textual representations more challenging (e.g., the manipulation over the data space cannot be easily achieved). Inspired by information theory, we propose a novel method that effectively manifests disentangled representations of text, without any supervision on semantics. A new mutual information upper bound is derived and leveraged to measure dependence between style and content. By minimizing this upper bound, the proposed method induces style and content embeddings into two independent low-dimensional spaces. Experiments on both conditional text generation and text-style transfer demonstrate the high quality of our disentangled representation in terms of content and style preservation.

In spite of achieving revolutionary successes in machine learning, deep convolutional neural networks have been recently found to be vulnerable to adversarial attacks and difficult to generalize to novel test images with reasonably large geometric transformations. Inspired by a recent neuroscience discovery revealing that primate brain employs disentangled shape and appearance representations for object recognition, we propose a general disentangled deep autoencoding regularization framework that can be easily applied to any deep embedding based classification model for improving the robustness of deep neural networks. Our framework effectively learns disentangled appearance code and geometric code for robust image classification, which is the first disentangling based method defending against adversarial attacks and complementary to standard defense methods. Extensive experiments on several benchmark datasets show that, our proposed regularization framework leveraging disentangled embedding significantly outperforms traditional unregularized convolutional neural networks for image classification on robustness against adversarial attacks and generalization to novel test data.