Understanding the fitness of protein variants with combinatorial mutations is critical for effective protein engineering. In this issue of Cell Systems, Chu et al. present TopVIP, a top variant identification pipeline that enables accurate picking of the greatest number of best-performing protein variants with high-fitness leveraging zero-shot predictor and low-N iterative sampling. Understanding the fitness of protein variants with combinatorial mutations is critical for effective protein engineering. In this issue of Cell Systems, Chu et al. present TopVIP, a top variant identification pipeline that enables accurate picking of the greatest number of best-performing protein variants with high-fitness leveraging zero-shot predictor and low-N iterative sampling. Accurate top protein variant discovery via low-N pick-and-validate machine learningChu et al.Cell SystemsFebruary 9, 2024In BriefProtein engineering involves the screening of a vast combinatorial mutational landscape. We present a top-performing protein variant identification strategy that only requires experimentation on a few selected variants in large combinatorial mutant libraries. Full-Text PDF