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Geometric characterisation of disease modules.

Franziska Härtner1, Miguel A Andrade-Navarro2, Gregorio Alanis-Lobato2

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Complex systems, like the human protein network, exhibit hyperbolic geometry. This geometry helps understand disease modules and protein communication, revealing disease mechanisms.

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Area of Science:

  • Systems Biology
  • Network Science
  • Computational Biology

Background:

  • Complex systems, including the human protein network (hPIN), are increasingly understood to possess an underlying hyperbolic geometry.
  • This latent geometry aids in visualizing protein-protein interactions and solving systems biology problems by measuring protein distances.
  • Proteins utilize a greedy routing (GR) process guided by hyperbolic distances for efficient communication within the hPIN.

Purpose of the Study:

  • To geometrically characterize disease modules (DMs) within the human protein network.
  • To investigate how the spatial arrangement of DMs in hyperbolic space reflects disease characteristics.
  • To explore the impact of defective proteins on signal transduction using GR strategies.

Main Methods:

  • Geometric characterization of disease modules on a 2D hyperbolic plane.
  • Utilizing a distance-based dissimilarity measure for clustering DMs with shared clinical features.
  • Applying the greedy routing (GR) strategy to analyze signal transduction disruptions.

Main Results:

  • Disease module positions on the hyperbolic plane indicate their fragmentation and functional heterogeneity, offering insights into affected cellular processes.
  • Clustering of DMs based on shared clinical features was achieved using a novel distance-based dissimilarity measure.
  • Analysis revealed how defective proteins impact signal transduction pathways through the hPIN.

Conclusions:

  • The hyperbolic geometry of the hPIN provides a powerful framework for understanding disease mechanisms.
  • Geometric characterization of DMs offers a novel approach to studying disease heterogeneity and affected cellular functions.
  • The study highlights the importance of efficient protein communication for cellular function and disease pathogenesis.