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


Type
Article
Change log
Authors
Vavouraki, Nikoleta 
Tomkins, James E 
Kara, Eleanna 
Houlden, Henry 
Hardy, John 
Abstract

The Hereditary Spastic Paraplegias are a group of neurodegenerative diseases characterized by spasticity and weakness in the lower body. Owing 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.

Description
Keywords
Bioinformatics, Biological sciences, Molecular network, Network
Journal Title
iScience
Conference Name
Journal ISSN
2589-0042
2589-0042
Volume Title
24
Publisher
Elsevier BV
Sponsorship
Medical Research Council (MR/N026004/1)