A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for "orphan" receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets.

A Culture of Understanding: Reflections and Suggestions from a Genomics Research Community Board.

There has been limited community engagement in the burgeoning field of genomics research. In the wake of a new discovery of genetic variants that increase the risk of kidney failure and are almost unique to people of African ancestry, community and clinical leaders in Harlem, New York, formed a community board to inform the direction of related research. The board advised all aspects of a study to assess the impact of testing for these genetic variants at primary care sites that serve diverse populations, including explaining genetic risk to participants. By reflecting on the board's experiences, we found that community voices can have tangible impact on research that navigates the controversial intersection of race, ancestry, and genomics by heightening vigilance, fostering clear communication between researchers and the community, and encouraging researchers to cede some control. Our reflections and work provide a strong justification for longitudinal community partnerships in genomics research.