Spatial Transcriptomics (ST) technologies provide biologists with rich insights into single-cell biology by preserving spatial context of cells. Building foundational models for ST can significantly enhance the analysis of vast and complex data sources, unlocking new perspectives on the intricacies of biological tissues. However, modeling ST data is inherently challenging due to the need to extract multi-scale information from tissue slices containing vast numbers of cells. This process requires integrating macro-scale tissue morphology, micro-scale cellular microenvironment, and gene-scale gene expression profile. To address this challenge, we propose **SToFM**, a multi-scale **S**patial **T**ranscript**o**mics **F**oundation **M**odel. SToFM first performs multi-scale information extraction on each ST slice, to construct a set of ST sub-slices that aggregate macro-, micro- and gene-scale information. Then an SE(2) Transformer is used to obtain high-quality cell representations from the sub-slices. Additionally, we construct **SToCorpus-88M**, the largest high-resolution spatial transcriptomics corpus for pretraining. SToFM achieves outstanding performance on a variety of downstream tasks, such as tissue region semantic segmentation and cell type annotation, demonstrating its comprehensive understanding of ST data through capturing and integrating multi-scale information.

This paper presents CPL-IQA, a novel semi-supervised blind image quality assessment (BIQA) framework for authentic distortion scenarios. To address the challenge of limited labeled data in IQA area, our approach leverages confidence-quantifiable pseudo-label learning to effectively utilize unlabeled authentically distorted images. The framework operates through a preprocessing stage and two training phases: first converting MOS labels to vector labels via entropy minimization, followed by an iterative process that alternates between model training and label optimization. The key innovations of CPL-IQA include a manifold assumption-based label optimization strategy and a confidence learning method for pseudo-labels, which enhance reliability and mitigate outlier effects. Experimental results demonstrate the framework’s superior performance on real-world distorted image datasets, offering a more standardized semi-supervised learning paradigm without requiring additional supervision or network complexity.

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding cell identity from the transcriptomic data, such as annotating cell types, has become an important task in bioinformatics. As these semantic aspects are determined by human experts, it is impossible for AI models to effectively carry out cell identity understanding tasks without the supervision signals provided by single-cell and label pairs. The single-cell pre-trained language models (PLMs) currently used for this task are trained only on a single modality, transcriptomics data, lack an understanding of cell identity knowledge. As a result, they have to be fine-tuned for downstream tasks and struggle when lacking labeled data with the desired semantic labels. To address this issue, we propose an innovative solution by constructing a unified representation of single-cell data and natural language during the pre-training phase, allowing the model to directly incorporate insights related to cell identity. More specifically, we introduce **LangCell**, the first **Lang**uage-**Cell** pre-training framework. LangCell utilizes texts enriched with cell identity information to gain a profound comprehension of cross-modal knowledge. Results from experiments conducted on different benchmarks show that LangCell is the only single-cell PLM that can work effectively in zero-shot cell identity understanding scenarios, and also significantly outperforms existing models in few-shot and fine-tuning cell identity understanding scenarios.

Studying protein mutations within amino acid sequences holds tremendous significance in life sciences. Protein language models (PLMs) have demonstrated strong capabilities in broad biological applications. However, due to architectural design and lack of supervision, PLMs model mutations implicitly with evolutionary plausibility, which is not satisfactory to serve as explainable and engineerable tools in real-world studies. To address these issues, we present MutaPLM, a unified framework for interpreting and navigating protein mutations with protein language models. MutaPLM introduces a protein *delta* network that captures explicit protein mutation representations within a unified feature space, and a transfer learning pipeline with a chain-of-thought (CoT) strategy to harvest protein mutation knowledge from biomedical texts. We also construct MutaDescribe, the first large-scale protein mutation dataset with rich textual annotations, which provides cross-modal supervision signals. Through comprehensive experiments, we demonstrate that MutaPLM excels at providing human-understandable explanations for mutational effects and prioritizing novel mutations with desirable properties. Our code, model, and data are open-sourced at https://github.com/PharMolix/MutaPLM.