Gene Regulatory Network Inference from Pre-trained Single-Cell Transcriptomics Transformer with Joint Graph Learning

Inferring gene regulatory networks (GRNs) from single-cell RNA sequencing (scRNA-seq) data is a complex challenge that requires capturing the intricate relationships between genes and their regulatory interactions. In this study, we tackle this challenge by leveraging the single-cell BERT-based pre-trained transformer model (scBERT), trained on extensive unlabeled scRNA-seq data, to augment structured biological knowledge from existing GRNs. We introduce a novel joint graph learning approach that combines the rich contextual representations learned by pre-trained single-cell language models with the structured knowledge encoded in GRNs using graph neural networks (GNNs). By integrating these two modalities, our approach effectively reasons over boththe gene expression level constraints provided by the scRNA-seq data and the structured biological knowledge inherent in GRNs. We evaluate our method on human cell benchmark datasets from the BEELINE study with cell type-specific ground truth networks. The results demonstrate superior performance over current state-of-the-art baselines, offering a deeper understanding of cellular regulatory mechanisms.

AI for Biomedicine in the Era of Large Language Models

The capabilities of AI for biomedicine span a wide spectrum, from the atomic level, where it solves partial differential equations for quantum systems, to the molecular level, predicting chemical or protein structures, and further extending to societal predictions like infectious disease outbreaks. Recent advancements in large language models, exemplified by models like ChatGPT, have showcased significant prowess in natural language tasks, such as translating languages, constructing chatbots, and answering questions. When we consider biomedical data, we observe a resemblance to natural language in terms of sequences: biomedical literature and health records presented as text, biological sequences or sequencing data arranged in sequences, or sensor data like brain signals as time series. The question arises: Can we harness the potential of recent large language models to drive biomedical knowledge discoveries? In this survey, we will explore the application of large language models to three crucial categories of biomedical data: 1) textual data, 2) biological sequences, and 3) brain signals. Furthermore, we will delve into large language model challenges in biomedical research, including ensuring trustworthiness, achieving personalization, and adapting to multi-modal data representation