MONTAGE: A Computation Framework to Identify Spatially Resolved Functional Enrichment Gradients in the Tissue Microenvironment via Spatial Communities.

Single-cell spatial-omics has advanced our understanding of how tumor microenvironment contributes to cancer progression. However, most single-cell spatial-omics studies focus on cell types and neighborhoods, offering limited information about functional and clinical relevance of cellular organization. We introduce MONTAGE, a computational framework to reconstruct, functionally analyze, and identify clinically relevant cellular spatial communities (SCs).

Spatially organized inflammatory myeloid-CD8 T cell aggregates linked to Merkel-cell Polyomavirus driven Reorganization of the Tumor Microenvironment.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with high propensity for metastasis, caused by Merkel-cell-polyomavirus (MCPyV), or chronic UV-light-exposure. How MCPyV spatially modulates immune responses within the tumor microenvironment and how such are linked to patient outcomes remains unknown. We interrogated the cellular and transcriptional landscapes of 60 MCC-patients using a combination of multiplex proteomics, RNA-hybridization, and spatially oriented transcriptomics.

Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood.

Multimodal and spatially resolved profiling identifies distinct patterns of T cell infiltration in nodal B cell lymphoma entities.

The redirection of T cells has emerged as an attractive therapeutic principle in B cell non-Hodgkin lymphoma (B-NHL). However, a detailed characterization of lymphoma-infiltrating T cells across B-NHL entities is missing. Here we present an in-depth T cell reference map of nodal B-NHL, based on cellular indexing of transcriptomes and epitopes, T cell receptor sequencing, flow cytometry and multiplexed immunofluorescence applied to 101 lymph nodes from patients with diffuse large B cell, mantle cell, follicular or marginal zone lymphoma, and from healthy controls.

A real-time GPU-accelerated parallelized image processor for large-scale multiplexed fluorescence microscopy data.

Highly multiplexed, single-cell imaging has revolutionized our understanding of spatial cellular interactions associated with health and disease. With ever-increasing numbers of antigens, region sizes, and sample sizes, multiplexed fluorescence imaging experiments routinely produce terabytes of data. Fast and accurate processing of these large-scale, high-dimensional imaging data is essential to ensure reliable segmentation and identification of cell types and for characterization of cellular neighborhoods and inference of mechanistic insights.

Multicellular modules as clinical diagnostic and therapeutic targets.

The complex determinants of health and disease can be determined when approached as a system of interactions of biological agents at different scales. Similar to the physicochemical properties that govern nucleic acids and proteins, there should be a finite set of rules that dictate the behavior of cells to form tissues. Thus, the occurrence of disease can be seen as flaws in processes that are governed by rules pertaining to multicellular structures.