Journal Article

Fast activation maximization for molecular sequence design

Linder, Johannes, Seelig, Georg

2021

Overview

Background Optimization of DNA and protein sequences based on Machine Learning models is becoming a powerful tool for molecular design. Activation maximization offers a simple design strategy for differentiable models: one-hot coded sequences are first approximated by a continuous representation, which is then iteratively optimized with respect to the predictor oracle by gradient ascent. While elegant, the current version of the method suffers from vanishing gradients and may cause predictor pathologies leading to poor convergence. Results Here, we introduce Fast SeqProp, an improved activation maximization method that combines straight-through approximation with normalization across the parameters of the input sequence distribution. Fast SeqProp overcomes bottlenecks in earlier methods arising from input parameters becoming skewed during optimization. Compared to prior methods, Fast SeqProp results in up to 100-fold faster convergence while also finding improved fitness optima for many applications. We demonstrate Fast SeqProp’s capabilities by designing DNA and protein sequences for six deep learning predictors, including a protein structure predictor. Conclusions Fast SeqProp offers a reliable and efficient method for general-purpose sequence optimization through a differentiable fitness predictor. As demonstrated on a variety of deep learning models, the method is widely applicable, and can incorporate various regularization techniques to maintain confidence in the sequence designs. As a design tool, Fast SeqProp may aid in the development of novel molecules, drug therapies and vaccines.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Activation maximization / Algorithms / Amino Acid Sequence / Approximation / Bioinformatics / Biomedical and Life Sciences / Computational Biology/Bioinformatics / Computer Appl. in Life Sciences / Convergence / Deep learning / Deoxyribonucleic acid / Design / Design optimization / Design techniques / DNA / Fitness / Gene sequencing / Learning algorithms / Life Sciences / Machine Learning / Mathematical models / Maximization / Methodology / Methodology Article / Methods / Microarrays / Neural networks / Nucleotide sequence / Optimization / Parameters / Probability distribution / Protein / Protein structure / Proteins / Regularization / RNA / Sequence design