Protein–protein interaction network with machine learning models and multiomics data reveal potential neurodegenerative disease-related proteins

2020 ◽  
Vol 29 (8) ◽  
pp. 1378-1387 ◽  
Author(s):  
Xinjian Yu ◽  
Siqi Lai ◽  
Hongjun Chen ◽  
Ming Chen

Abstract Research of protein–protein interaction in several model organisms is accumulating since the development of high-throughput experimental technologies and computational methods. The protein–protein interaction network (PPIN) is able to examine biological processes in a systematic manner and has already been used to predict potential disease-related proteins or drug targets. Based on the topological characteristics of the PPIN, we investigated the application of the random forest classification algorithm to predict proteins that may cause neurodegenerative disease, a set of pathological changes featured by protein malfunction. By integrating multiomics data, we further showed the validity of our machine learning model and narrowed down the prediction results to several hub proteins that play essential roles in the PPIN. The novel insights into neurodegeneration pathogenesis brought by this computational study can indicate promising directions for future experimental research.

2021 ◽  
Author(s):  
Nikoleta Vavouraki ◽  
James E. Tomkins ◽  
Eleanna Kara ◽  
Henry Houlden ◽  
John Hardy ◽  
...  

AbstractThe Hereditary Spastic Paraplegias are a group of neurodegenerative diseases characterized by spasticity and weakness in the lower body. Despite the identification of causative mutations in over 70 genes, the molecular aetiology remains unclear. 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 protein-protein interactions were used to create a protein-protein interaction network based on the causative Hereditary Spastic Paraplegia genes. Network evaluation as a combination of both 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, suggesting 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.


2019 ◽  
Vol 15 (6) ◽  
pp. 431-441 ◽  
Author(s):  
Dibyajyoti Das ◽  
Sowmya Ramaswamy Krishnan ◽  
Arijit Roy ◽  
Gopalakrishnan Bulusu

To understand disease pathogenesis, all the disease-related proteins must be identified. In this work, known proteins were used to identify related novel proteins using RWR method on a dynamic P. falciparum protein–protein interaction network.


2017 ◽  
Vol 8 (Suppl 1) ◽  
pp. S20-S21 ◽  
Author(s):  
Akram Safaei ◽  
Mostafa Rezaei Tavirani ◽  
Mona Zamanian Azodi ◽  
Alireza Lashay ◽  
Seyed Farzad Mohammadi ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document