Article
Multiplex and multimodal mapping of variant effects in secreted proteins via MultiSTEP.
Nature structural & molecular biology - 1 Oct 2025
Popp Nicholas A, Powell Rachel L, Wheelock Melinda K, Holmes Kristen J, Zapp Brendan D, Sheldon Kathryn M, Fletcher Shelley N, Wu Xiaoping, Fayer Shawn, Rubin Alan F, Lannert Kerry W, Chang Alexis T, Sheehan John P, Johnsen Jill M, Fowler Douglas M
Abstract excerpt
Despite widespread advances in DNA sequencing, the functional consequences of most genetic variants remain poorly understood. Multiplexed assays of variant effect can measure the function of variants at scale but cannot readily be applied to the ~10% of human genes encoding secreted proteins. Here we develop a flexible, scalable human cell surface display method, multiplexed surface tethering of extracellular...
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