Statistical and Machine Learning Approaches for Network Analysis

9.2 Datasets and Methods

9.2.1 Microarray Dataset and Protein–Protein Interaction Data

The AD microarray dataset (GSE5281) in GEO database [35] was used for the analysis, including 13 control samples and 10 AD samples collected from the entorhinal cortex region in the brains of AD patients with a mean age of 79.8 ± 9.1 years. The intensities of the probe-sets were first normalized by robust microarray adjustment (RMA) and logarithmized to base two. The expressions of the multiple probes for the same genes on the microarray were then averaged. Experimental PPI data was collected from two major protein interaction databases for human, including BioGRID [36] and HPRD [37]. Duplicate and self-interactions were removed from the analysis.

9.2.2 Calculation of the Synergy Scores of Gene Pairs

An information theory-based score was calculated to quantify the synergy between the genes [34]. Given two genes, G1 and G2, and a phenotype P, the synergy score between G1 and G2 with respect to the phenotype P is defined as

where I(G1;P) is the mutual information between G1 and P, I(G2;P) is the mutual information between G2 and P, and I(G1,G2;P) is the mutual information between (G1,G2) and P. This equation reflects the definition of synergy, the additional contribution provided by the “whole” as compared to the sum of the contributions of the individual “parts.” Mutual information (I) was calculated ...