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.

Science, Ahead of Print.

Nature Biotechnology, Published online: 31 March 2026; doi:10.1038/s41587-026-03068-6Simultaneous profiling of adenylated and non-adenylated RNAs reveals regulatory programs across diverse cell types.