Tools4Cells: A high-throughput platform for identifying protein-protein interactions using pooled immunoprecipitation-mass spectrometry and sparse signal recovery

This award will enable the development of an integrated experimental and computational platform that accelerates the discovery of protein-protein interactions (PPIs). PPIs are important in governing numerous processes like development and the onset of pathological conditions such as cancer and neurodegenerative disease. PPIs form extensive networks that vary across time, conditions, and cell types, creating a complex and high-dimensional problem. There is a pressing need for universally applicable tools that can comprehensively and efficiently map these networks. The platform developed in the project will accomplish this by transforming the mapping problem into a mathematical one that is easier to solve. The award will also support three undergraduate students, one graduate student and two postdoctoral scholars to receive interdisciplinary training that combines proteomics and computational biology. This project will take a new approach to network mapping by transforming the problem into a compressed mathematical space that can be analyzed more efficiently. To implement this compression, the platform will combine an algorithmically optimized pooling scheme, immunopurification-mass spectrometry, and a novel sparse signal reconstruction algorithm. By increasing the throughput of PPI discovery, the platform will democratize the study of regulated protein interactions for researchers with varying resources. It will also empower scientists to construct medium- to large-scale PPI networks across multiple conditions, fostering transformative discoveries in the biological sciences. Additionally, it holds promise for industry applications, particularly in therapeutic antibody screens, making such research more accessible and impactful. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.