The metabolomic physics of complex diseases

Shuang Wu, Xiang Liu, Ang Dong, Claudia Gragnoli, Christopher Griffin, Jie Wu, Shing Tung Yau, Rongling Wu

Research output: Contribution to journalArticlepeer-review


Human diseases involve metabolic alterations. Metabolomic profiles have served as a vital biomarker for the early identification of high-risk individuals and disease prevention. However, current approaches can only characterize individual key metabolites, without taking into account the reality that complex diseases are multifactorial, dynamic, heterogeneous, and interdependent. Here, we leverage a statistical physics model to combine all metabolites into bidirectional, signed, and weighted interaction networks and trace how the flow of information from one metabolite to the next causes changes in health state. Viewing a disease outcome as the consequence of complex interactions among its interconnected components (metabolites), we integrate concepts from ecosystem theory and evolutionary game theory to model how the health state-dependent alteration of a metabolite is shaped by its intrinsic properties and through extrinsic influences from its conspecifics. We code intrinsic contributions as nodes and extrinsic contributions as edges into quantitative networks and implement GLMY homology theory to analyze and interpret the topological change of health state from symbiosis to dysbiosis and vice versa. The application of this model to real data allows us to identify several hub metabolites and their interaction webs, which play a part in the formation of inflammatory bowel diseases. The findings by our model could provide important information on drug design to treat these diseases and beyond.

Original languageEnglish (US)
Article numbere2308496120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - 2023

All Science Journal Classification (ASJC) codes

  • General

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