Table 1.
Suppressors of the Aβ-paralysis phenotype.
Table 2.
Enhancers of the Aβ-paralysis phenotype.
Table 3.
Gene ontology enrichment for worm screen hits.
Figure 1.
The +1 interaction network for the 52 GWAS genes with intermediate and high significance (p<105). For the 52 genes in the GWAS white+grey zones, there were 703 interactions in the +1 interactome.
Figure 2.
The +1 interaction network for the human orthologues of the 60 worm genes that were highlighted in our worm RNAi screen. For the 60 worm-screen genes with human orthologues, there were 3191 interactions in the +1 interactome.
Figure 3.
Distribution of rankings of worm genes.
The x-axis represents the log of the gene ranking bin boundaries, arranged in decreasing gene-product connectedness from left to right. The y-axis represents the log of the fraction of genes in each bin (where 100% is 60 genes). The dashed line shows the linear regression for the worm screen results. The results of the screens are shown as black diamonds and results of random simulations are shown as empty triangles.
Figure 4.
Distribution of rankings of worm models of neurodegenerative diseases.
The x-axis represents the log of the gene ranking bin boundaries, arranged in decreasing gene-product connectedness from left to right. The y-axis represents the log of the fraction of genes in each bin (where 100% is 135, 23, 22 & 52 genes for panels A, B, C & D respectively). The dashed line shows the linear regression for the worm screen results. The results of the screens are shown as black diamonds and results of random simulations are shown as empty triangles. (A) polyglutamine screen; (B) α-synuclein screen; (C) tau screen; (D) GWAS candidate white+grey zone genes for AD.
Figure 5.
The interaction network of 4 significant worm gene products.
Four human orthologues of worm screen gene products (MOB4, TCP1, CCT8 and ACTB) have +1 interactomes that overlap more than expected with the +1 interactome of the GWAS white+grey gene products. Two of these are components of the abundant cytoplasmic TRiC/CCT chaperone, the third (MOB4) interacts closely and fourth (ACTB), along with tubulin, is an important substrate. TRiC/CCT interacts with STK24 and PP2a to form a complex that regulates the MAPK pathway. This network of interactions may have a bearing on tau phosphorylation and neuronal regeneration.
Table 4.
Overlap between the +1 interactome for the products of genes in the GWAS white+grey zone and those of genes in the +1 interactome of the worm RNAi screen.