Computational Drug Discovery and Design

Chapter 10

Building Molecular Interaction Networks from Microarray

Data for Drug Target Screening

Sze Chung Yuen, Hongmei Zhu, and Siu-wai Leung

Abstract

Potential drug targets for the disease treatment can be identified from microarray studies on differential
gene expression of patients and healthy participants. Here, we describe a method to use the information of
differentially expressed (DE) genes obtained from microarray studies to build molecular interaction net-
works for identification of pivotal molecules as potential drug targets. The quality control and normaliza-
tion of the microarray data are conducted with R packagessimpleaffyandaffy, respectively. The DE genes
with adjustedPvalues less than 0.05 and log fold changes larger than 1 or less than
1 are identified by
limmapackage to construct a molecular interaction network with InnateDB. The genes with significant
connectivity are identified by the Cytoscape appjActiveModules. The interactions among the genes within a
module are tested bypsychpackage to determine their associations. The gene pairs with significant associa-
tion and known protein structures according to the Protein Data Bank are selected as potential drug targets.
As an example for drug target screening, we demonstrate how to identify potential drug targets from a
molecular interaction network constructed with the DE genes of significant connectivity, using a microarray
dataset of type 2 diabetes mellitus.

Key wordsDifferentially expressed genes, Drug targets, Microarray, R, Type 2 diabetes mellitus

1 Introduction

Microarrays are a high-throughput technology to determine differ-

ential gene expression [1, 2]. For example, the Affymetrix platform

can detect the expression of 20,000–40,000 genes simultaneously

[3]. Its capability is adequate to cover major genes in human

genome [4, 5]. Affymetrix applies a probe set to interrogate a single

gene. The expression ratios estimated from significantly different

signal intensities within a probe set should be consistent [6].

Microarray technology allows researchers to detect dysregula-

tion in gene expression that would help diagnose and understand

Mohini Gore and Umesh B. Jagtap (eds.),Computational Drug Discovery and Design, Methods in Molecular Biology, vol. 1762,
https://doi.org/10.1007/978-1-4939-7756-7_10,©Springer Science+Business Media, LLC, part of Springer Nature 2018

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