Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport

Abstract Understanding disease progression is crucial for detecting critical transitions and finding trigger molecules, facilitating early diagnosis interventions. However, the high dimensionality of data and the lack of aligned samples across disease stages have posed challenges in addressing these...

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Main Authors: Wenbo Hua, Ruixia Cui, Heran Yang, Jingyao Zhang, Chang Liu, Jian Sun
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07995-z
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author Wenbo Hua
Ruixia Cui
Heran Yang
Jingyao Zhang
Chang Liu
Jian Sun
author_facet Wenbo Hua
Ruixia Cui
Heran Yang
Jingyao Zhang
Chang Liu
Jian Sun
author_sort Wenbo Hua
collection DOAJ
description Abstract Understanding disease progression is crucial for detecting critical transitions and finding trigger molecules, facilitating early diagnosis interventions. However, the high dimensionality of data and the lack of aligned samples across disease stages have posed challenges in addressing these tasks. We present a computational framework, Gaussian Graphical Optimal Transport (GGOT), for analyzing disease progressions. The proposed GGOT uses Gaussian graphical models, incorporating protein interaction networks, to characterize the data distributions at different disease stages. Then we use population-level optimal transport to calculate the Wasserstein distances and transport between stages, enabling us to detect critical transitions. By analyzing the per-molecule transport distance, we quantify the importance of each molecule and identify trigger molecules. Moreover, GGOT predicts the occurrence of critical transitions in unseen samples and visualizes the disease progression process. We apply GGOT to the simulation dataset and six disease datasets with varying disease progression rates to substantiate its effectiveness. Compared to existing methods, our proposed GGOT exhibits superior performance in detecting critical transitions.
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spelling doaj-art-cfb4d716e6e84c55a88a28b2aa94db442025-08-20T03:07:44ZengNature PortfolioCommunications Biology2399-36422025-04-018111810.1038/s42003-025-07995-zUncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transportWenbo Hua0Ruixia Cui1Heran Yang2Jingyao Zhang3Chang Liu4Jian Sun5School of Mathematics and Statistics, Xi’an Jiaotong UniversityKey Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Ministry of EducationSchool of Mathematics and Statistics, Xi’an Jiaotong UniversityKey Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Ministry of EducationKey Laboratory of Surgical Critical Care and Life Support (Xi’an Jiaotong University), Ministry of EducationSchool of Mathematics and Statistics, Xi’an Jiaotong UniversityAbstract Understanding disease progression is crucial for detecting critical transitions and finding trigger molecules, facilitating early diagnosis interventions. However, the high dimensionality of data and the lack of aligned samples across disease stages have posed challenges in addressing these tasks. We present a computational framework, Gaussian Graphical Optimal Transport (GGOT), for analyzing disease progressions. The proposed GGOT uses Gaussian graphical models, incorporating protein interaction networks, to characterize the data distributions at different disease stages. Then we use population-level optimal transport to calculate the Wasserstein distances and transport between stages, enabling us to detect critical transitions. By analyzing the per-molecule transport distance, we quantify the importance of each molecule and identify trigger molecules. Moreover, GGOT predicts the occurrence of critical transitions in unseen samples and visualizes the disease progression process. We apply GGOT to the simulation dataset and six disease datasets with varying disease progression rates to substantiate its effectiveness. Compared to existing methods, our proposed GGOT exhibits superior performance in detecting critical transitions.https://doi.org/10.1038/s42003-025-07995-z
spellingShingle Wenbo Hua
Ruixia Cui
Heran Yang
Jingyao Zhang
Chang Liu
Jian Sun
Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport
Communications Biology
title Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport
title_full Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport
title_fullStr Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport
title_full_unstemmed Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport
title_short Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport
title_sort uncovering critical transitions and molecule mechanisms in disease progressions using gaussian graphical optimal transport
url https://doi.org/10.1038/s42003-025-07995-z
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