The Best Thing Since Sliced Tissue: A Glimpse into the Future with GPSA

a,b, A superposition of the histology images of the two slices in the unaligned and aligned coordinate systems, respectively. c,d, Magnified versions of the region in the red bounding box. e, The same data as d, but the points for the second slice are shown with arrows pointing in the direction of the alignment.1

In the heart of San Francisco’s bustling Mission Bay neighbourhood, a groundbreaking innovation is taking shape. Researchers from the esteemed Gladstone Institutes have unveiled a pioneering method that could hold the key to moving our understanding of biological tissues forward in a dramatic fashion.

A Sliced Approach to Understanding Tissues

Imagine having just a few slices from a loaf of bread and trying to visualize the entire loaf. This analogy mirrors the challenges faced by scientists who aim to understand the three-dimensional structure of biological tissues using only two-dimensional slices. The difficulties are compounded when we consider the inherent warping of tissue samples during lab procedures.

However, Dr. Barbara Engelhardt and her team from Gladstone Institutes have brought forward a computational solution that promises to revolutionize this domain: the Gaussian Process Spatial Alignment (GPSA).

The Science Behind GPSA

GPSA operates on a unique two-layer Gaussian process. In layman’s terms, it reverses the warping seen in 2D tissue slices and reconstructs them in a 3D virtual model. This process doesn’t just stop at aligning these slices but goes a step further, filling the spaces between them. It offers predictions on gene or protein expressions at every point, providing researchers with a comprehensive 3D “atlas” of the tissue.

This adaptability of GPSA is particularly noteworthy. Not only can it manage slices of varying sizes and resolutions, but it also accommodates data from different technologies. Furthermore, it can merge various types of tissue data – from gene expressions to cellular structures – into one cohesive atlas.

Broader Implications for Healthcare

The potential applications of GPSA are vast. It opens doors to new insights into tumors, allowing healthcare professionals to pinpoint exact locations for treatments. By providing a thorough understanding of how illnesses progress or how different tissues evolve over time, it promises more targeted interventions and treatments.

For labs operating on tighter budgets, GPSA offers a beacon of hope. Dr. Engelhardt’s team is working on methodologies that can determine the minimum number of tissue slices needed for effective analysis. This not only conserves resources but also maximizes the insights derived from the available samples.

A Collaborative Triumph

The groundbreaking study, “Alignment of Spatial Genomics and Histology Data Using Deep Gaussian Processes,” was a collaborative effort. Published in the renowned journal Nature Methods on August 17, 2023, it boasted contributions from Didong Li from the University of North Carolina, Chapel Hill, and Andrew Jones and F. William Townes of Carnegie Mellon University.

With financial backing from notable organizations like the Helmsley Charitable Trust, the National Institutes of Health, and the National Science Foundation, this research stands as a testament to the power of collaboration and innovative thinking.


In an era where biomedical breakthroughs are critical, Gladstone Institutes’ GPSA methodology stands out as a beacon of hope. By bridging the gap between 2D slices and 3D tissue models, it offers a glimpse into a future where our understanding of human biology and health could reach unprecedented heights.

  1. Jones, A., Townes, F.W., Li, D. et al. Alignment of spatial genomics data using deep Gaussian processes. Nat Methods 20, 1379–1387 (2023).

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