Fig. 4

L3 provides mechanistic insights into protein function and complex diseases. For two proteins involved in retinitis pigmentosa (RP), FAM161A and PRPF31, we show all known interacting partners in HI-tested (gray), together with those predicted by the L3 algorithm and confirmed by pairwise tests (blue). The top L3 predicted interaction is connecting FAM161A to GOLGA2, two proteins without any shared interaction partners. The node size and color illustrates the degree of the proteins in HI-tested. In light of our experiments, GOLGA2, TRIM23, and TRIM54 are now amongst several shared interaction partners between FAM161A and PRPF31, a pre-mRNA splicing factor, whose mutations are causal for another form of RP³⁰. This illustrates the key principle behind L3 (Fig. 1d), that two proteins, like FAM161A and PRPF31, despite sharing multiple interacting partners, do not necesseraly interact with each other, but share additional, previously unrecognized interaction partners