Comprehensive Metapath-based Heterogeneous Graph Transformer for Gene-Disease Association Prediction

Discovering gene-disease associations is crucial for understanding disease mechanisms, yet identifying these associations remains challenging due to the time and cost of biological experiments. Computational methods are increasingly vital for efficient and scalable gene-disease association prediction. Graph-based learning models, which leverage node features and network relationships, are commonly employed for biomolecular predictions. However, existing methods often struggle to effectively integrate node features, heterogeneous structures, and semantic information. To address these challenges, we propose COmprehensive MEtapath-based heterogeneous graph Transformer(COMET) for predicting gene-disease associations. COMET integrates diverse datasets to construct comprehensive heterogeneous networks, initializing node features with BioGPT. We define seven Metapaths and utilize a transformer framework to aggregate Metapath instances, capturing global contexts and long-distance dependencies. Through intra- and inter-metapath aggregation using attention mechanisms, COMET fuses latent vectors from multiple Metapaths to enhance GDA prediction accuracy. Our method demonstrates superior robustness compared to state-of-the-art approaches. Ablation studies and visualizations validate COMET's effectiveness, providing valuable insights for advancing human health research.

Knowledge-Guided Biomarker Identification for Label-Free Single-Cell RNA-Seq Data: A Reinforcement Learning Perspective

Gene panel selection aims to identify the most informative genomic biomarkers in label-free genomic datasets. Traditional approaches, which rely on domain expertise, embedded machine learning models, or heuristic-based iterative optimization, often introduce biases and inefficiencies, potentially obscuring critical biological signals. To address these challenges, we present an iterative gene panel selection strategy that harnesses ensemble knowledge from existing gene selection algorithms to establish preliminary boundaries or prior knowledge, which guide the initial search space. Subsequently, we incorporate reinforcement learning through a reward function shaped by expert behavior, enabling dynamic refinement and targeted selection of gene panels. This integration mitigates biases stemming from initial boundaries while capitalizing on RL's stochastic adaptability. Comprehensive comparative experiments, case studies, and downstream analyses demonstrate the effectiveness of our method, highlighting its improved precision and efficiency for label-free biomarker discovery. Our results underscore the potential of this approach to advance single-cell genomics data analysis.

scReader: Prompting Large Language Models to Interpret scRNA-seq Data

Large language models (LLMs) have demonstrated remarkable advancements, primarily due to their capabilities in modeling the hidden relationships within text sequences. This innovation presents a unique opportunity in the field of life sciences, where vast collections of single-cell omics data from multiple species provide a foundation for training foundational models. However, the challenge lies in the disparity of data scales across different species, hindering the development of a comprehensive model for interpreting genetic data across diverse organisms. In this study, we propose an innovative hybrid approach that integrates the general knowledge capabilities of LLMs with domain-specific representation models for single-cell omics data interpretation. We begin by focusing on genes as the fundamental unit of representation. Gene representations are initialized using functional descriptions, leveraging the strengths of mature language models such as LLaMA-2. By inputting single-cell gene-level expression data with prompts, we effectively model cellular representations based on the differential expression levels of genes across various species and cell types. In the experiments, we constructed developmental cells from humans and mice, specifically targeting cells that are challenging to annotate. We evaluated our methodology through basic tasks such as cell annotation and visualization analysis. The results demonstrate the efficacy of our approach compared to other methods using LLMs, highlighting significant improvements in accuracy and interoperability. Our hybrid approach enhances the representation of single-cell data and offers a robust framework for future research in cross-species genetic analysis.

GeneSUM: Large Language Model-based Gene Summary Extraction

Emerging topics in biomedical research are continuously expanding, providing a wealth of information about genes and their function. This rapid proliferation of knowledge presents unprecedented opportunities for scientific discovery and formidable challenges for researchers striving to keep abreast of the latest advancements. One significant challenge is navigating the vast corpus of literature to extract vital gene-related information, a time-consuming and cumbersome task. To enhance the efficiency of this process, it is crucial to address several key challenges: (1) the overwhelming volume of literature, (2) the complexity of gene functions, and (3) the automated integration and generation. In response, we propose GeneSUM, a two-stage automated gene summary extractor utilizing a large language model (LLM). Our approach retrieves and eliminates redundancy of target gene literature and then fine-tunes the LLM to refine and streamline the summarization process. We conducted extensive experiments to validate the efficacy of our proposed framework. The results demonstrate that LLM significantly enhances the integration of gene-specific information, allowing more efficient decision-making in ongoing research.

Towards Graph Prompt Learning: A Survey and Beyond

Large-scale "pre-train and prompt learning" paradigms have demonstrated remarkable adaptability, enabling broad applications across diverse domains such as question answering, image recognition, and multimodal retrieval. This approach fully leverages the potential of large-scale pre-trained models, reducing downstream data requirements and computational costs while enhancing model applicability across various tasks. Graphs, as versatile data structures that capture relationships between entities, play pivotal roles in fields such as social network analysis, recommender systems, and biological graphs. Despite the success of pre-train and prompt learning paradigms in Natural Language Processing (NLP) and Computer Vision (CV), their application in graph domains remains nascent. In graph-structured data, not only do the node and edge features often have disparate distributions, but the topological structures also differ significantly. This diversity in graph data can lead to incompatible patterns or gaps between pre-training and fine-tuning on downstream graphs. We aim to bridge this gap by summarizing methods for alleviating these disparities. This includes exploring prompt design methodologies, comparing related techniques, assessing application scenarios and datasets, and identifying unresolved problems and challenges. This survey categorizes over 100 relevant works in this field, summarizing general design principles and the latest applications, including text-attributed graphs, molecules, proteins, and recommendation systems. Through this extensive review, we provide a foundational understanding of graph prompt learning, aiming to impact not only the graph mining community but also the broader Artificial General Intelligence (AGI) community.

BioRAG: A RAG-LLM Framework for Biological Question Reasoning

The question-answering system for Life science research, which is characterized by the rapid pace of discovery, evolving insights, and complex interactions among knowledge entities, presents unique challenges in maintaining a comprehensive knowledge warehouse and accurate information retrieval. To address these issues, we introduce BioRAG, a novel Retrieval-Augmented Generation (RAG) with the Large Language Models (LLMs) framework. Our approach starts with parsing, indexing, and segmenting an extensive collection of 22 million scientific papers as the basic knowledge, followed by training a specialized embedding model tailored to this domain. Additionally, we enhance the vector retrieval process by incorporating a domain-specific knowledge hierarchy, which aids in modeling the intricate interrelationships among each query and context. For queries requiring the most current information, BioRAG deconstructs the question and employs an iterative retrieval process incorporated with the search engine for step-by-step reasoning. Rigorous experiments have demonstrated that our model outperforms fine-tuned LLM, LLM with search engines, and other scientific RAG frameworks across multiple life science question-answering tasks.

GUME: Graphs and User Modalities Enhancement for Long-Tail Multimodal Recommendation

Multimodal recommendation systems (MMRS) have received considerable attention from the research community due to their ability to jointly utilize information from user behavior and product images and text. Previous research has two main issues. First, many long-tail items in recommendation systems have limited interaction data, making it difficult to learn comprehensive and informative representations. However, past MMRS studies have overlooked this issue. Secondly, users' modality preferences are crucial to their behavior. However, previous research has primarily focused on learning item modality representations, while user modality representations have remained relatively simplistic.To address these challenges, we propose a novel Graphs and User Modalities Enhancement (GUME) for long-tail multimodal recommendation. Specifically, we first enhance the user-item graph using multimodal similarity between items. This improves the connectivity of long-tail items and helps them learn high-quality representations through graph propagation. Then, we construct two types of user modalities: explicit interaction features and extended interest features. By using the user modality enhancement strategy to maximize mutual information between these two features, we improve the generalization ability of user modality representations. Additionally, we design an alignment strategy for modality data to remove noise from both internal and external perspectives. Extensive experiments on four publicly available datasets demonstrate the effectiveness of our approach.

Enhancing Tabular Data Optimization with a Flexible Graph-based Reinforced Exploration Strategy

Tabular data optimization methods aim to automatically find an optimal feature transformation process that generates high-value features and improves the performance of downstream machine learning tasks. Current frameworks for automated feature transformation rely on iterative sequence generation tasks, optimizing decision strategies through performance feedback from downstream tasks. However, these approaches fail to effectively utilize historical decision-making experiences and overlook potential relationships among generated features, thus limiting the depth of knowledge extraction. Moreover, the granularity of the decision-making process lacks dynamic backtracking capabilities for individual features, leading to insufficient adaptability when encountering inefficient pathways, adversely affecting overall robustness and exploration efficiency. To address the limitations observed in current automatic feature engineering frameworks, we introduce a novel method that utilizes a feature-state transformation graph to effectively preserve the entire feature transformation journey, where each node represents a specific transformation state. During exploration, three cascading agents iteratively select nodes and idea mathematical operations to generate new transformation states. This strategy leverages the inherent properties of the graph structure, allowing for the preservation and reuse of valuable transformations. It also enables backtracking capabilities through graph pruning techniques, which can rectify inefficient transformation paths. To validate the efficacy and flexibility of our approach, we conducted comprehensive experiments and detailed case studies, demonstrating superior performance in diverse scenarios.

Enhanced Gene Selection in Single-Cell Genomics: Pre-Filtering Synergy and Reinforced Optimization

Recent advancements in single-cell genomics necessitate precision in gene panel selection to interpret complex biological data effectively. Those methods aim to streamline the analysis of scRNA-seq data by focusing on the most informative genes that contribute significantly to the specific analysis task. Traditional selection methods, which often rely on expert domain knowledge, embedded machine learning models, or heuristic-based iterative optimization, are prone to biases and inefficiencies that may obscure critical genomic signals. Recognizing the limitations of traditional methods, we aim to transcend these constraints with a refined strategy. In this study, we introduce an iterative gene panel selection strategy that is applicable to clustering tasks in single-cell genomics. Our method uniquely integrates results from other gene selection algorithms, providing valuable preliminary boundaries or prior knowledge as initial guides in the search space to enhance the efficiency of our framework. Furthermore, we incorporate the stochastic nature of the exploration process in reinforcement learning (RL) and its capability for continuous optimization through reward-based feedback. This combination mitigates the biases inherent in the initial boundaries and harnesses RL's adaptability to refine and target gene panel selection dynamically. To illustrate the effectiveness of our method, we conducted detailed comparative experiments, case studies, and visualization analysis.

Dynamic and Adaptive Feature Generation with LLM

The representation of feature space is a crucial environment where data points get vectorized and embedded for upcoming modeling. Thus the efficacy of machine learning (ML) algorithms is closely related to the quality of feature engineering. As one of the most important techniques, feature generation transforms raw data into an optimized feature space conducive to model training and further refines the space. Despite the advancements in automated feature engineering and feature generation, current methodologies often suffer from three fundamental issues: lack of explainability, limited applicability, and inflexible strategy. These shortcomings frequently hinder and limit the deployment of ML models across varied scenarios. Our research introduces a novel approach adopting large language models (LLMs) and feature-generating prompts to address these challenges. We propose a dynamic and adaptive feature generation method that enhances the interpretability of the feature generation process. Our approach broadens the applicability across various data types and tasks and draws advantages over strategic flexibility. A broad range of experiments showcases that our approach is significantly superior to existing methods.