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Fast and interpretable quantification of biological shape heterogeneity via stratified Wasserstein kernel
Wenjun Zhao1, Danica J Sutherland2,3, Khanh Dao Duc4
1Department of Mathematics, Wake Forest University, Winston-Salem, North Carolina, United States of America.
Plos Computational Biology
|May 7, 2026
Summary
We developed a new framework for comparing shapes from biological imaging data. This method enables robust population-level shape analysis and reveals key differences in cellular structures.
Area of Science:
- Computational Biology
- Biophysics
- Data Science
Background:
- Modern imaging generates large datasets of cellular structures.
- Existing methods for shape comparison are insufficient for large-scale population analysis.
- Principled methods are needed for isometry-invariant shape comparison.
Purpose of the Study:
- Introduce a novel framework for analyzing and comparing shapes from biological imaging.
- Enable statistically rigorous, population-level shape analysis for large datasets.
- Provide a tool for identifying key morphological differences in biological populations.
Main Methods:
- Developed the stratified Wasserstein framework for shape analysis.
- Embedded shapes as point clouds into Euclidean space using ranked local distance profiles.
- Utilized kernel methods for nonparametric hypothesis testing and population analysis.
- Created a sample-based estimator supporting large datasets in near-quadratic time.
Main Results:
- The framework provides an isometry-invariant Euclidean distance and a positive-definite kernel.
- Demonstrated applicability to large-scale 2D cancer cell contour data, quantifying population discrepancies.
- Identified representative cells contributing to observed differences in cancer cell populations.
- Analyzed 3D cell envelope and nucleus volumes to reveal progression patterns and morphological changes.
Conclusions:
- The stratified Wasserstein framework is a simple, principled tool for population-level biological shape analysis.
- The method offers theoretical guarantees and interpretability for shape comparison tasks.
- Potential impact across computational imaging, data science, and diverse biological research domains.

