Omer Bar-Tal

Abstract Understanding the spatial organization of tissues is of critical importance for both basic and translational research. While recent advances in tissue imaging are opening an exciting new window into the biology of human tissues, interpreting the data that they create is a significant computational challenge. Cell segmentation, the task of uniquely identifying each cell in an image, remains a substantial barrier for tissue imaging, as existing approaches are inaccurate or require a substantial amount of manual curation to yield useful results. Here, we addressed the problem of cell segmentation in tissue imaging data through large-scale data annotation and deep learning. We constructed TissueNet, an image dataset containing >1 million paired whole-cell and nuclear annotations for tissue images from nine organs and six imaging platforms. We created Mesmer, a deep learning-enabled segmentation algorithm trained on TissueNet that performs nuclear and whole-cell segmentation in tissue imaging data. We demonstrated that Mesmer has better speed and accuracy than previous methods, generalizes to the full diversity of tissue types and imaging platforms in TissueNet, and achieves human-level performance for whole-cell segmentation. Mesmer enabled the automated extraction of key cellular features, such as subcellular localization of protein signal, which was challenging with previous approaches. We further showed that Mesmer could be adapted to harness cell lineage information present in highly multiplexed datasets. We used this enhanced version to quantify cell morphology changes during human gestation. All underlying code and models are released with permissive licenses as a community resource.

We present a method for semantically transferring the visual appearance of one natural image to another. Specifically, our goal is to generate an image in which objects in a source structure image are “painted” with the visual appearance of their semantically related objects in a target appearance image. Our method works by training a generator given only a single structure/appearance image pair as input. To integrate semantic information into our framework—a pivotal component in tackling this task-our key idea is to leverage a pre-trained and fixed Vision Transformer (ViT) model which serves as an external semantic prior. Specifically, we derive novel representations of structure and appearance extracted from deep ViT features, untwisting them from the learned self-attention modules. We then establish an objective function that splices the desired structure and appearance representations, interweaving them together in the space of ViT features. Our framework, which we term “Splice”, does not involve adversarial training, nor does it require any additional input information such as semantic segmentation or correspondences, and can generate high resolution results, e.g., work in HD. We demonstrate high quality results on a variety of in-the-wild image pairs, under significant variations in the number of objects, their pose and appearance.