Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology (original) (raw)
Figure 1
Pictorial outline of methodology.
A. Genes overlapping the wingspan of associated SNPs are defined, and these genes code for associated proteins. B. Associated proteins are used to recover direct and indirect networks. Direct networks (left) are built from direct interactions between associated proteins according to the InWeb database (colored proteins). Connections between proteins within the same locus are not considered. Indirect networks (right) are built by allowing connections between associated proteins through a protein elsewhere in the genome (grey). Various network parameters to quantify connectivity, defined in the text, are assigned. C. Random networks are built from a within-degree node-label permutation method described in Text S1. An empirical distribution is constructed for each network parameter and used to evaluate the significance of networks. D. Using the same permutation method to score individual proteins, a subset of proteins per locus is nominated as candidates for harboring causal variants (red circles). Scores used to nominate candidates, described in Text S1, are Bonferroni corrected for the number of possible candidates within each locus. E. Candidate genes from D (nominal p-values used) are tested for co-expression.