Designing Distributed Cell Classifier Circuits using a Genetic Algorithm

Cell classifiers are decision-making synthetic circuits that allow in vivo cell-type classification. Their design is based on finding a relationship between differential expression of miRNAs and the cell condition. Such biological devices have shown potential to become a valuable tool in cancer treatment as a new type-specific cell targeting approach. So far, only single-circuit classifiers were designed in this context. However, reliable designs come with high complexity, making them difficult to assemble in the lab. Here, we apply so-called Distributed Classifiers (DC) consisting of simple single circuits, that decide collectively according to a threshold function. Such architecture potentially simplifies the assembly process and provides design flexibility. Here, we present a genetic algorithm that allows the design and optimization of DCs. Breast cancer case studies show that DCs perform with high accuracy on real-world data. Optimized classifiers capture biologically relevant miRNAs that are cancer-type specific. The comparison to a single-circuit classifier design approach shows that DCs perform with significantly higher accuracy than individual circuits. The algorithm is implemented as an open source tool.