Deep learning has significantly advanced numerous fields by training on extensive annotated datasets. However, this data-driven paradigm faces limitations such as limited adaptability and high annotation costs, particularly when precise adherence to detailed, domain-specific guidelines is required in annotation. This challenge raises a critical question: Can models effectively shift from data-driven learning to autonomously leveraging guidelines with minimal annotated examples? To address this, we propose the Guideline-Driven Prompt (GDP) optimization framework, which shifts the learning paradigm from data-driven training to guideline-driven reasoning. GDP leverages Retrieval Augmented Generation (RAG) to retrieve essential fragments from complex guidelines and synthesize them into structured, executable prompts. A tree-based optimization algorithm systematically constructs and refines these prompts, explicitly capturing the intricate logic embedded in professional guidelines through a latent pipeline structure. Empirical evaluations on four datasets ranging from diverse domains and different tasks demonstrate that GDP effectively transitions the learning process from data-intensive methods to a guideline-driven approach in tasks requiring detailed and complex guideline adherence, reducing dependence on extensive annotated datasets.

Exploring the functions of genes and gene products is crucial to a wide range of fields, including medical research, evolutionary biology, and environmental science. However, discovering new functions largely relies on expensive and exhaustive wet lab experiments. Existing methods of automatic function annotation or prediction mainly focus on protein function prediction with sequence, 3D-structures or protein family information. In this study, we propose to tackle the gene function prediction problem by exploring Gene Ontology graph and annotation with BERT (GoBERT) to decipher the underlying relationships among gene functions. Our proposed novel function prediction task utilizes existing functions as inputs and generalizes the function prediction to gene and gene products. Specifically, two pre-train tasks are designed to jointly train GoBERT to capture both explicit and implicit relations of functions. Neighborhood prediction is a self-supervised multi-label classification task that captures the explicit function relations. Specified masking and recovering task helps GoBERT in finding implicit patterns among functions. The pre-trained GoBERT possess the ability to predict novel functions for various gene and gene products based on known functional annotations. Extensive experiments, biological case studies, and ablation studies are conducted to demonstrate the superiority of our proposed GoBERT.

Molecular property prediction aims to learn representations that map chemical structures to functional properties. While multimodal learning has emerged as a powerful paradigm to learn molecular representations, prior works have largely overlooked textual and taxonomic information of molecules for representation learning. We introduce TRIDENT, a novel framework that integrates molecular SMILES, textual descriptions, and taxonomic functional annotations to learn rich molecular representations. To achieve this, we curate a comprehensive dataset of molecule-text pairs with structured, multi-level functional annotations. Instead of relying on conventional contrastive loss, TRIDENT employs a volume-based alignment objective to jointly align tri-modal features at the global level, enabling soft, geometry-aware alignment across modalities. Additionally, TRIDENT introduces a novel local alignment objective that captures detailed relationships between molecular substructures and their corresponding sub-textual descriptions. A momentum-based mechanism dynamically balances global and local alignment, enabling the model to learn both broad functional semantics and fine-grained structure-function mappings. TRIDENT achieves state-of-the-art performance on 18 downstream tasks, demonstrating the value of combining SMILES, textual, and taxonomic functional annotations for molecular property prediction. Our code and data are available at https://github.com/uta-smile/TRIDENT.

In the rapidly evolving field of AI research, foundational models like BERT and GPT have significantly advanced language and vision tasks. The advent of pretrain-prompting models, such as ChatGPT and segment anything model (SAM), has further revolutionized image segmentation. However, their applications in specialized areas, particularly in nuclei segmentation within medical imaging, reveal a key challenge: the generation of high-quality, informative prompts is as crucial as applying state-of-the-art (SOTA) fine-tuning techniques on foundation models. To address this, we introduce segment any cell (SAC), an innovative framework that enhances SAM specifically for nuclei segmentation. SAC integrates a low-rank adaptation (LoRA) within the attention layer of the Transformer to improve the fine-tuning process, outperforming existing SOTA methods. It also introduces an innovative auto-prompt generator that produces effective prompts to guide segmentation, a critical factor in handling the complexities of nuclei segmentation in biomedical imaging. Our extensive experiments demonstrate the superiority of SAC in nuclei segmentation tasks, proving its effectiveness as a tool for pathologists and researchers. Our contributions include a novel prompt generation strategy, automated adaptability for diverse segmentation tasks, the innovative application of low-rank attention adaptation in SAM, and a versatile framework for semantic and instance segmentation challenges.

The interaction between T-cell receptors (TCRs) and peptides (epitopes) presented by major histocompatibility complex molecules (MHC) is fundamental to the immune response. Accurate prediction of TCR-epitope interactions is crucial for advancing the understanding of various diseases and their prevention and treatment. Existing methods primarily rely on sequence-based approaches, overlooking the inherent topology structure of TCR-epitope interaction networks. In this study, we present $GTE$, a novel heterogeneous Graph neural network model based on inductive learning to capture the topological structure between TCRs and Epitopes. Furthermore, we address the challenge of constructing negative samples within the graph by proposing a dynamic edge update strategy, enhancing model learning with the nonbinding TCR-epitope pairs. Additionally, to overcome data imbalance, we adapt the Deep AUC Maximization strategy to the graph domain. Extensive experiments are conducted on four public datasets to demonstrate the superiority of exploring underlying topological structures in predicting TCR-epitope interactions, illustrating the benefits of delving into complex molecular networks. The implementation code and data are available at https://github.com/uta-smile/GTE.