A novel multi-layer prediction approach for sweetness evaluation based on systematic machine learning modeling

Abstract Nowadays, computational approaches have drawn more and more attention when exploring the relationship between sweetness and chemical structure instead of traditional experimental tests. In this work, we proposed a novel multi-layer sweetness evaluation system based on machine learning methods. It can be used to evaluate sweet properties of compounds with different chemical spaces and categories, including natural, artificial, carbohydrate, non-carbohydrate, nutritive and non-nutritive ones, suitable for different application scenarios. Furthermore, it provides quantitative predictions of sweetness. In addition, sweetness-related chemical basis and structure transforming rules were obtained by using molecular cloud and matched molecular pair analysis (MMPA) methods. This work systematically improved the data quality, explored the best machine learning algorithm and molecular characterizing strategy, and finally obtained robust models to establish a multi-layer prediction system (available at: https://github.com/ifyoungnet/ChemSweet ). We hope that this study could facilitate food scientists with efficient screening and precise development of high-quality sweeteners.