Drawing inspiration from Hilbert’s list of 23 mathematical problems that have focused the mathematical community’s attention for more than a century, we propose fifteen grand AI challenges to focus the biomedical community’s attention on critically relevant questions, most of which still lack effective predictive methodologies.

Sprox-seq enables spatial profiling of protein complexes, surface proteins, and mRNAs in intact tissues by combining proximity ligation with spatial transcriptomics. In human tonsils, Sprox-seq maps germinal center interaction networks, links CD21-CD35 complexes to proliferative programs, reveals interaction-based B cell state transitions, and directly captures B cell-follicular dendritic cell communication.