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
Sreedevi Chandrasekaran, Danail Bonchev

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...Continue Reading

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Citations

Dec 16, 2018·Cells·Alexandru Florin RogobeteMihaela Viviana Ivan
Apr 7, 2019·Briefings in Bioinformatics·Jianjian WangLihua Wang
Feb 2, 2020·Interdisciplinary Sciences, Computational Life Sciences·Fuzhang YangJiang Xie
Nov 17, 2020·Frontiers in Neuroscience·Yuhai ZhaoWalter J Lukiw

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Datasets Mentioned

BETA
GSE4757
GSE28146

Methods Mentioned

BETA
protein modification
ChIP-Seq
transgenic

Software Mentioned

IPA
Database for Annotation , Visualization and Integrated Discove...
Pajek
Pathway Studio
R
DAVID
Bioconductor
limma Bioconductor

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