Abstract: Methods for determining a property that affects expression of polynucleotides are provided. A plurality of polynucleotides each encoding a polypeptide sequence is constructed. A frequency that a sequence element is used in a first polynucleotide is different than in a second polynucleotide. Each polynucleotide is expressed in an expression system to obtain an expression property value thereby constructing a dataset that contains, for each respective polynucleotide, sequence element occurrence in the respective polynucleotide and the measured expression property value of the respective polynucleotide. A model is computed that describes variation in the measured expression property values as a function of a plurality of variables and weights.