Fig. 10: Analysis of pathway, disease, and mutation links as well as network-based measures.

a Bar chart showing the percentage of three relevance factors for the set of new high-confidence (HC, n = 160 proteins) substrates compared to a set comprising all known substrates and new HC substrates. Total numbers are indicated within the respective bars. Only pathway and disease links were considered that were not linked before to γ-secretase or its known substrates. b Bar chart showing the number of disease links from (a), as classified by disease classes from DisGeNET. c Chord diagram illustrating the number of links for new pathways and disease terms from (b) for the 20 new HC substrates with the highest number of new links (Supplementary Data 17). Substrates are sorted alphabetically, and validated ones are highlighted in red. Note that mitochondrial proteins, such as TOMM70 (highlighted in (c) by an asterisk), although unlikely γ-secretase substrates, were not excluded to keep our analysis unbiased. d Box plots for network metrics comparing the four confidence-based substrate classes (see Methods “Confidence-based substrate classes” for sample sizes). Differences between HC substrates and the other classes were tested using a two-sided Mann–Whitney U-test with separate Bonferroni correction. Significance levels are indicated by color-coded asterisks (*P < 0.05, **P < 0.01, ***P < 0.001). Source data are provided as a Source Data file.