Integrating network, sequence and functional features using machine learning approaches towards identification of novel Alzheimer genes

BMC Genomics

Research Article

Asheesh Shanker¹  Abhinav Grover²  Salma Jamal³  Sukriti Goyal³ 

[1] Bioinformatics Programme, Centre for Biological Sciences, Central University of South Bihar, BIT Campus, Patna, Bihar, India;School of Biotechnology, Jawaharlal Nehru University, 110067, New Delhi, India;School of Biotechnology, Jawaharlal Nehru University, 110067, New Delhi, India;Department of Bioscience and Biotechnology, Banasthali University, 304022, Tonk, Rajasthan, India;

关键词: Alzheimer-associated genes;    Machine learning;    Interaction networks;    Sequence features;    Functional annotations;    Molecular docking;    Molecular dynamics;   

DOI  :  10.1186/s12864-016-3108-1

 received in 2016-04-29, accepted in 2016-09-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAlzheimer’s disease (AD) is a complex progressive neurodegenerative disorder commonly characterized by short term memory loss. Presently no effective therapeutic treatments exist that can completely cure this disease. The cause of Alzheimer’s is still unclear, however one of the other major factors involved in AD pathogenesis are the genetic factors and around 70 % risk of the disease is assumed to be due to the large number of genes involved. Although genetic association studies have revealed a number of potential AD susceptibility genes, there still exists a need for identification of unidentified AD-associated genes and therapeutic targets to have better understanding of the disease-causing mechanisms of Alzheimer’s towards development of effective AD therapeutics.ResultsIn the present study, we have used machine learning approach to identify candidate AD associated genes by integrating topological properties of the genes from the protein-protein interaction networks, sequence features and functional annotations. We also used molecular docking approach and screened already known anti-Alzheimer drugs against the novel predicted probable targets of AD and observed that an investigational drug, AL-108, had high affinity for majority of the possible therapeutic targets. Furthermore, we performed molecular dynamics simulations and MM/GBSA calculations on the docked complexes to validate our preliminary findings.ConclusionsTo the best of our knowledge, this is the first comprehensive study of its kind for identification of putative Alzheimer-associated genes using machine learning approaches and we propose that such computational studies can improve our understanding on the core etiology of AD which could lead to the development of effective anti-Alzheimer drugs.

【 授权许可】

CC BY   
© The Author(s). 2016