MechanoMaST - a multimodal pipeline for spatially registering mechanical and transcriptomic tissue data

Spatial-omics workflows allow for the analysis of molecular information within the context of tissue structure. However, they have not yet integrated direct mechanical measurements, such as tissue stiffness, which carries prognostic value. The reason for this lack of incorporation is due to several obstacles, including the need for substantial samples, low throughput, specialized equipment, and complex data registration processes.

In this study, researchers have developed mechanoMaST, the first workflow to integrate absolute mechanical measurements with spatial-omics data.

MechanoMaST combines nanoindentation stiffness maps, generated through atomic force microscopy, with spatial transcriptomics maps obtained from adjacent tissue cryosections. These two modalities are computationally co-registered, enabling a direct spatial correlation at a resolution of 100 micrometers. The mapping accuracy is evaluated using error propagation techniques, which provide ground-truth mechanical data that is directly correlated with spatial gene expression.

The researchers applied mechanoMaST to human colorectal cancer liver metastasis samples from ten patients, resulting in a spatial resource that identifies a four-gene stiffness signature.

The mechanoMaST workflow is easily adaptable to other tissues across various stages of development and disease. Furthermore, it can be extended to incorporate additional spatial-omics modalities from adjacent sections, making it a versatile tool for future research.