High-Quality Binary Protein Interaction Map of the Yeast Interactome Network

TLDR

Yeast interactome maps are limited in binary interaction coverage, and Y2H and AP/MS provide complementary high‑quality data that generate networks with distinct topological and biological properties. The authors aimed to develop an empirically controlled mapping framework to produce a second‑generation high‑quality, high‑throughput Y2H dataset covering approximately 20 % of all yeast binary interactions. They implemented an empirically controlled high‑throughput Y2H mapping framework to generate this dataset. Comparative assessment showed that high‑throughput Y2H yields high‑quality binary interactions, and the resulting map is enriched for transient signaling and intercomplex connections with essential‑protein clustering, while protein connectivity correlates with genetic pleiotropy rather than essentiality.

Abstract

Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a “second-generation” high-quality, high-throughput Y2H data set covering ∼20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry (AP/MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy.