Tiangang Wang

Jiajia Liu, Mengyuan Yang, Yankai Yu et al.

Large language models (LLMs) are a class of artificial intelligence models based on deep learning, which have great performance in various tasks, especially in natural language processing (NLP). Large language models typically consist of artificial neural networks with numerous parameters, trained on large amounts of unlabeled input using self-supervised or semi-supervised learning. However, their potential for solving bioinformatics problems may even exceed their proficiency in modeling human language. In this review, we will provide a comprehensive overview of the essential components of large language models (LLMs) in bioinformatics, spanning genomics, transcriptomics, proteomics, drug discovery, and single-cell analysis. Key aspects covered include tokenization methods for diverse data types, the architecture of transformer models, the core attention mechanism, and the pre-training processes underlying these models. Additionally, we will introduce currently available foundation models and highlight their downstream applications across various bioinformatics domains. Finally, drawing from our experience, we will offer practical guidance for both LLM users and developers, emphasizing strategies to optimize their use and foster further innovation in the field.

Zhiwei Fan, Tiangang Wang, Kexin Huang et al.

Recent advances in spatial omics technologies have revolutionized our ability to study biological systems with unprecedented resolution. By preserving the spatial context of molecular measurements, these methods enable comprehensive mapping of cellular heterogeneity, tissue architecture, and dynamic biological processes in developmental biology, neuroscience, oncology, and evolutionary studies. This review highlights a systematic overview of the continuous advancements in both technology and computational algorithms that are paving the way for a deeper, more systematic comprehension of the structure and mechanisms of mammalian tissues and organs by using spatial multi-omics. Our viewpoint demonstrates how advanced machine learning algorithms and multi-omics integrative modeling can decode complex biological processes, including the spatial organization and topological relationships of cells during organ development, as well as key molecular signatures and regulatory networks underlying tumorigenesis and metastasis. Finally, we outline future directions for technological innovation and modeling insights of spatial omics in precision medicine.