Figure 4.

Hub-Protein Knockdown Results Are Consistent with Network-Based Predictions of Hub Centrality and Efficacy

(A) Chemotaxis levels of uninduced C. elegans adults (strain CL2355, with pan-neuronal leaky expression of human Aβ₄₂), declined to an average chemotaxis index (C.I.) of 0.27 at 5 days of adult age (FV bars). C.I. levels (shown as mean ± S.E.M. for triplicate experiments) are higher for RNAi-treated worms, indicating up to 54% rescue relative to day 1 adult worms (C.I. ≈ 0.9). Knockdown targets were nematode orthologs or homologs of randomly selected human proteins identified in each indicated hub category, from the cross-link-defined contactome of SY5Y-APP_Sw neuroblastoma cells. Numbers over bars indicate the unadjusted significance (p values) of hub RNAi knockdowns differing from FV controls, based on heteroscedastic two-tailed paired t tests, considering the C.I. from each of three independent experiments as a single data point. **Unadjusted chi-squared (χ²) significance of p ≤ 0.001, combined from three independent experiments, i.e., the product of three χ² p values comparing treated worms to their simultaneous controls.

(B) Network diagram of the SY5Y-APP_Sw contactome, displaying for each hub its degree (number of interactions; see key for node sizes) and the neural network prediction of knockdown efficacy (rescue of chemotaxis as determined in [A]; see key for node colors).

(C) Network diagram of control data, a scale-free network generated with the same node sizes as in (B). In a scale-free network, the degree distribution follows a power law; real-world networks, including protein-protein interaction networks, are widely considered to be scale-free. The distributions of node sizes, edges, and knockdown efficacies are here far more uniform than in the interactome based on empirically observed interactions (B).