New Method Aligns Data from Tissue Slices Virtually to Expand Possibilities for 3D Analysis

The new method, named Gaussian Process Spatial Alignment (GPSA) which has been developed by researchers at Gladstone Institutes (San Francisco, CA, USA) has a scope extending beyond tumors, encompassing a wide array of tissues and data derived from tissue slices. This innovative method leverages a two-layer Gaussian process. In the first layer, it aligns the warped two-dimensional tissue slice onto a three-dimensional tissue model. The second layer attributes data collected from the slice, such as activated genes, to each point in the three-dimensional model. This intelligent approach effectively reverses the warping effect, resulting in a precise alignment of the slices. During this process, the GPSA model extrapolates data to fill the gaps between slices, generating a comprehensive three-dimensional "atlas" of the tissue.

A key advantage of GPSA is its versatility. Researchers can construct tissue atlases using data from slices of varying sizes, generated by diverse technologies, and captured at different scales and resolutions. Unlike previous techniques that demanded a predefined three-dimensional framework, GPSA derives this framework solely from the two-dimensional slices when an initial framework isn't available. Additionally, GPSA has the capability to merge multiple types of tissue-slice data, such as genetic activity and cellular structure, into a unified atlas. Furthermore, when applied to slices taken from the same tissue at different time points, GPSA can generate atlases that predict how each location within the tissue evolves over time. This feature could deepen our insights into aging, disease progression, and the development of different tissues within growing organisms. Presently, researchers are engaged in further analyses to further demonstrate the tool’s flexibility. For instance, they have devised an approach that budget-conscious labs can use to determine the minimum number of tissue slices required and the precise cutting locations needed for GPSA to build an informative tissue atlas.

“Say you have four slices from different locations in a person’s breast cancer tumor, and for every point on each slice you know which of 20,000 genes are turned on or off,” said Gladstone Senior Investigator Barbara Engelhardt, PhD, senior author of the study. “GPSA creates a fully query-able 3D atlas where, for any single ‘x, y, z’ coordinate, for any of the 20,000 genes, we can dive in and ask: What genes are on and off at this position in the tumor? And how certain are we in this estimate?”

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