Simplifying complex antibody engineering using machine learning

Abstract

Machine learning is transforming antibody engineering by enabling the generation of drug-like monoclonal antibodies with unprecedented efficiency. Unsupervised algorithms trained on massive and diverse protein sequence datasets facilitate the prediction of panels of antibody variants with native-like intrinsic properties (e.g., high stability), greatly reducing the amount of subsequent experimentation needed to identify specific candidates that also possess desired extrinsic properties (e.g., high affinity). Additionally, supervised algorithms, which are trained on deep sequencing datasets obtained after enrichment of in vitro antibody libraries for one or more specific extrinsic properties, enable the prediction of antibody variants with desired combinations of extrinsic properties without the need for additional screening. Here we review recent advances using both machine learning approaches and how they are impacting the field of antibody engineering as well as key outstanding challenges and opportunities for these paradigm-changing methods.

Keywords: CDR; IgG; affinity; antigen; complementarity-determining region; deep learning; directed evolution; mAb; protein design; stability; variable region.