Network Topology Analysis of Post-Mortem Brain Microarrays Identifies More Alzheimer’s Related Genes and MicroRNAs and Points to Novel Routes for Fighting with the Disease

Authors

Sreedevi Chandrasekaran, Virginia Commonwealth UniversityFollow
Danail Bonchev, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2016

Journal/Book/Conference Title

PLOS ONE

Volume

11

Issue

1

DOI of Original Publication

10.1371/journal.pone.0144052

Comments

Originally published at http://dx.doi.org/10.1371/journal.pone.0144052

Correction: 9 Mar 2016: The PLOS ONE Staff (2016) Correction: Network Topology Analysis of Post-Mortem Brain Microarrays Identifies More Alzheimer's Related Genes and MicroRNAs and Points to Novel Routes for Fighting with the Disease. PLoS ONE 11(3): e0151122. doi: 10.1371/journal.pone.0151122 View correction

Date of Submission

March 2016

Abstract

Network-based approaches are powerful and beneficial tools to study complex systems in their entirety, elucidating the essential factors that turn the multitude of individual elements into a functional system. In this study we used critical network topology descriptors and guilt-by-association rule to explore and understand the significant molecular players, drug targets and underlying biological mechanisms of Alzheimer’s disease. Analyzing two post-mortem brain gene microarrays (GSE4757 and GSE28146) with Pathway Studio software package we constructed and analyzed a set of protein-protein interaction, as well as miRNA-target networks. In a 4-step procedure the expression datasets were normalized using Robust Multi-array Average approach, while the modulation of gene expression by the disease was statistically evaluated by the empirical Bayes method from the limma Bioconductor package. Representative set of 214 seed-genes (p<0.01) common for the three brain sections of the two microarrays was thus created. The Pathway Studio analysis of the networks built identified 15 new potential AD-related genes and 17 novel AD-involved microRNAs. Using KEGG pathways relevant in Alzheimer’s disease we built an integrated mechanistic network from the interactions between the overlapping genes in these pathways. Routes of possible disease initiation process were thus revealed through the CD4, DCN, and IL8 extracellular ligands. DAVID and IPA enrichment analysis uncovered a number of deregulated biological processes and pathways including neuron projection/differentiation, aging, oxidative stress, chemokine/ neurotrophin signaling, long-term potentiation and others. The findings in this study offer information of interest for subsequent experimental studies.

Rights

Copyright © 2016 Chandrasekaran, Bonchev. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Study of Biological Complexity Publications