Histology imaging is an important tool in medical diagnosis and research, enabling the examination of tissue structure and composition at the microscopic level. Understanding the underlying molecular mechanisms of tissue architecture is critical in uncovering disease mechanisms and developing effective treatments. Gene expression profiling provides insight into the molecular processes underlying tissue architecture, but the process can be time-consuming and expensive. We present BLEEP (Bi-modaL Embedding for Expression Prediction), a bi-modal embedding framework capable of generating spatially resolved gene expression profiles of whole-slide Hematoxylin and eosin (H&E) stained histology images. BLEEP uses contrastive learning to construct a low-dimensional joint embedding space from a reference dataset using paired image and expression profiles at micrometer resolution. With this approach, the gene expression of any query image patch can be imputed using the expression profiles from the reference dataset. We demonstrate BLEEP's effectiveness in gene expression prediction by benchmarking its performance on a human liver tissue dataset captured using the 10x Visium platform, where it achieves significant improvements over existing methods. Our results demonstrate the potential of BLEEP to provide insights into the molecular mechanisms underlying tissue architecture, with important implications in diagnosis and research of various diseases. The proposed approach can significantly reduce the time and cost associated with gene expression profiling, opening up new avenues for high-throughput analysis of histology images for both research and clinical applications.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyperparameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deeplearning algorithm that not only exceeds existing methods, but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging. Cell segmentation is a fundamental task that is universally required for biological image analysis across a large number of different experimental settings and imaging modalities. For example, in multiplexed fluorescence image-based cancer microenvironment analysis, cell segmentation is the prerequisite for the identification of tumor sub-types, composition, and organization, which can lead to important biological insights [1]-[3]. However, the development of a universal and automatic cell segmentation technique continues to pose significant challenges due to the extensive diversity observed in microscopy images. This diversity arises from variations in cell origins, microscopy types, staining techniques, and cell morphologies. Recent advances [4], [5] have successfully demonstrated the feasibility of automatic and precise cellular segmentation for specific microscopy image types and cell types, such as fluorescence and mass spectrometry images [6], [7], differential interference contrast images of platelets [8], bacteria images [9] and yeast images [10], [11], but the selection of appropriate segmentation models remains a non-trivial task for non-expert users in conventional biology laboratories. Efforts have been made towards the development of generalized cell segmentation algorithms [9], [12], [13]. However, these algorithms were primarily trained using datasets consisting of gray-scale images and two-channel fluorescent images, lacking the necessary diversity to ensure robust generalization across a wide range of imaging modalities. For example, the segmentation models have struggled to perform effectively on RGB images, such as bone marrow aspirate slides stained with Jenner-Giemsa. Furthermore, these models often require manual selection of both the model type and the specific image channel to be segmented, posing challenges for biologists with limited computational expertise. Biomedical image data science competitions have emerged as an effective way to accelerate the development of cutting-edge algorithms [14], [15].