Genetic landscape of an in vivo protein interactome.

Genetic variation influences in vivo protein-protein interactions in yeast, with 12,000 SNPs revealing 61 reporter PPIs and numerous piQTLs.

• Why it matters: Understanding how natural genetic differences affect PPIs is crucial for linking genetic variation to cellular function and complex traits, yet this relationship remains largely unexplored.
• What they did: The study measured PPI strength across yeast strains with extensive SNPs, identifying and validating piQTLs, especially trans-acting ones, in both coding and noncoding regions, including noncoding RNAs and 3'UTRs.
• The result: Findings show trans-piQTLs often target genes near PPIs in network space, overlap more with protein abundance QTLs, and enable detailed dissection of post-transcriptional regulation, advancing complex trait analysis.