Population Based Optimization for Biological Sequence Design

The use of black-box optimization for the design of new biological sequences is an emerging research area with potentially revolutionary impact. The cost and latency of wet-lab experiments requires methods that find good sequences in few experimental rounds of large batches of sequences --- a setting that off-the-shelf black-box optimization methods are ill-equipped to handle. We find that the performance of existing methods varies drastically across optimization tasks, posing a significant obstacle to real-world applications. To improve robustness, we propose population-based optimization (PBO), which generates batches of sequences by sampling from an ensemble of methods. The number of sequences sampled from any method is proportional to the quality of sequences it previously proposed, allowing PBO to combine the strengths of individual methods while hedging against their innate brittleness. Adapting the population of methods online using evolutionary optimization further improves performance. Through extensive experiments on in-silico optimization tasks, we show that PBO outperforms any single method in its population, proposing both higher quality single sequences as well as more diverse batches. By its robustness and ability to design diverse, high-quality sequences, PBO is shown to be a new state-of-the art approach to the batched black-box optimization of biological sequences.

• Health & Bioscience

• Machine Intelligence