Prediction of New Candidate Genes Related to AD and MDD

In this study, the PPIN data were obtained from the Protein Interaction Network Analysis (PINA) database (Cowley et al., 2012) by pooling and curating the unique physical interaction information from six main public protein interaction databases, i.e., BioGRID, IntAct, DIP, MINT, MIPS/MPact, and HPRD. In the meantime, Menche et al. (2015) reported an interactome for human that contained 141,296 edges among 13,460 nodes. Later, we merged the two interactomes data by excluding the self-interaction and redundant pairs. We excluded ubiquitin-C, B, and D (i.e., UBC, UBB, and UBD) from this network because of the non-specific binding of ubiquitin to proteins for degradation (Ferrari et al., 2018). Finally, we obtained a relatively complete human physical interactome, which included 15,435 genes/protein and 218,161 interactions (Supplementary Material 1).

We mapped the 650 AD-associated genes to the PPIN and obtained an AD-specific network containing 9,089 genes/protein and 32,065 interactions. Similarly, by mapping the 447 MDD-associated genes to the PPIN, we obtained an MDD-specific network containing 6,541 genes/protein and 18,221 interactions. Then, the irrelevant interactions were excluded by merging the AD-specific network and MDD-specific network into a single disease network, which contained 10,203 genes/protein and 45,385 interactions. Finally, the AD-specific network was compared against the MDD-specific network, and the overlapping part was extracted, and the node degree of each node in this overlapping network was calculated with the disease network as background via the “Network Analyzer” (Assenov et al., 2008) plug-in in the Cytoscape software. After removing AD-associated genes and MDD-associated genes, the remaining genes could be expected to be novel candidate genes for both diseases.