MOTIVATION: Synthesizing proteins in heterologous hosts is an important tool in biotechnology. However, the genetic code is degenerate and the codon usage is biased in many organisms. Synonymous codon changes that are customized for each host organism may have a significant effect on the level of protein expression. This effect can be measured by using metrics, such as codon adaptation index, codon pair bias, relative codon bias and relative codon pair bias. Codon optimization is designing codons that improve one or more of these objectives. Currently available algorithms and software solutions either rely on heuristics without providing optimality guarantees or are very rigid in modeling different objective functions and restrictions. RESULTS: We develop an effective mixed integer linear programing (MILP) formulation, which considers multiple objectives. Our numerical study shows that this formulation can be effectively used to generate (Pareto) optimal codon designs even for very long amino acid sequences using a standard commercial solver. We also show that one can obtain designs in the efficient frontier in reasonable solution times and incorporate other complex objectives, such as mRNA secondary structures in codon design using MILP formulations. AVAILABILITY AND IMPLEMENTATION: http://alpersen.bilkent.edu.tr/codonoptimization/CodonOptimization.zip.

Abstract We consider bilateral trade of an object between a seller and a buyer through an intermediary who aims to maximize his/her expected gains as in the previous study, in a Bayes‐Nash equilibrium framework where the seller and buyer have private, discrete valuations for the object. Using duality of linear network optimization, the intermediary's initial problem is transformed into an equivalent linear programming problem with explicit formulae of expected revenues of the seller and the expected payments of the buyer, from which the optimal mechanism is immediately obtained. Then, an extension of the same problem is considered for a risk‐averse intermediary. Through a computational analysis, we observe that the structure of the optimal mechanism is fundamentally changed by switching from risk‐neutral to risk‐averse environment.