title: Integrating network, sequence and functional features using machine learning approaches towards identification of novel Alzheimer genes.
abstract: Alzheimer'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.
  
  
  
  In 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.
  
  
  
  To 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.
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.|Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, 304022, India.
authors.forename: Salma
authors.initials: S
authors.lastname: Jamal
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.|Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, 304022, India.
authors.forename: Sukriti
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Bioinformatics Programme, Centre for Biological Sciences, Central University of South Bihar, BIT Campus, Patna, Bihar, India.
authors.forename: Asheesh
authors.initials: A
authors.lastname: Shanker
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India. abhinavgr@gmail.com.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D066264:Datasets as Topic; D020869:Gene Expression Profiling; D063990:Gene Ontology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D000069550:Machine Learning; D058977:Molecular Sequence Annotation; D025941:Protein Interaction Mapping; D015203:Reproducibility of Results
keywords: Alzheimer-associated genes; Functional annotations; Interaction networks; Machine learning; Molecular docking; Molecular dynamics; Sequence features