RPE-choroid AMD interactome: globally conserved and phenotype-specific subnetworks. (a) AMD interactome showing direct and indirect protein-protein interactions within RPE-choroid Global Up, CNV Up and GA Up disease modules assembled from three data sources: STRING , Ingenuity Pathway Analyzer (IPA), and the Bossi and Lehner  human protein-protein interaction dataset (PPI) (see Materials and methods). Gene products are represented by nodes, most of which are color-coded according to disease module. Yellow nodes represent genes predicted by IPA, with the exception of VEGFA, which was predicted manually and is highly expressed in our RPE-choroid expression data. Parallelogram-shaped nodes denote genes previously associated with AMD (Table S2 in Additional file 3). Individual immunoglobulin genes/probes in the Global Up module were combined (see Materials and methods) and are represented as a single node ('Ig'). Exp, Db, and Text indicate Experimental, Knowledge/Database, and Text-mining components of the STRING interaction score, respectively. (b) Heat maps depict differential expression of network genes in the macula of each AMD/pre-AMD phenotype (also see Figure S12 in Additional file 1). Differential expression was calculated as the geometric mean of each gene normalized to age-matched normal donor samples (≥ 60 years). Only pure GA and CNV are represented. (For data including GA/CNV donor samples, see Figure S12 in Additional file 1). (c) Bar plot depicting mean of expression data in (b), shown as a function of AMD/pre-AMD phenotype. Error bars represent standard error of the mean.