Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias

Output Details

Preprint January 16, 2021

Published April 28, 2021

The Hereditary Spastic Paraplegias are a group of neurodegenerative diseases characterized by spasticity and weakness in the lower body. Due to the combination of genetic diversity and variable clinical presentation, the Hereditary Spastic Paraplegias are a strong candidate for protein-protein interaction network analysis as a tool to understand disease mechanism(s) and to aid functional stratification of phenotypes. In this study, experimentally validated human data were used to create a protein-protein interaction network based on the causative genes. Network evaluation as a combination of topological analysis and functional annotation led to the identification of core proteins in putative shared biological processes, such as intracellular transport and vesicle trafficking. The application of machine learning techniques suggested a functional dichotomy linked with distinct sets of clinical presentations, indicating that there is scope to further classify conditions currently described under the same umbrella-term of Hereditary Spastic Paraplegias based on specific molecular mechanisms of disease.
Tags
  • Machine learning
  • Original Research
  • Protein-protein interaction

Meet the Authors

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    NikoletaVavouraki

  • James Tomkins, PhD

    Key Personnel: Team Wood

    University of Cambridge

  • User avatar fallback logo

    Eleanna Kara

  • User avatar fallback logo

    Henry Houlden

  • John Hardy, PhD

    Lead PI (Core Leadership): Team Hardy

    University College London

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    Marcus J. Tindal

  • Claudia Manzoni, PhD

    Key Personnel: Team Hardy

    University College London