SSH: A Tool for Predicting Hydrophobic Interaction of Monoclonal Antibodies Using Sequences

Abstract

Therapeutic antibodies are one of the most important parts of the pharmaceutical industry. They are widely used in treating various diseases such as autoimmune diseases, cancer, inflammation, and infectious diseases. Their development process however is often brought to a standstill or takes a longer time and is then more expensive due to their hydrophobicity problems. Hydrophobic interactions can cause problems on half-life, drug administration, and immunogenicity at all stages of antibody drug development. Some of the most widely accepted and used technologies for determining the hydrophobic interactions of antibodies include standup monolayer adsorption chromatography (SMAC), salt-gradient affinity-capture self-interaction nanoparticle spectroscopy (SGAC-SINS), and hydrophobic interaction chromatography (HIC). However, to measure SMAC, SGAC-SINS, and HIC for hundreds of antibody drug candidates is time-consuming and costly. To save time and money, a predictor called SSH is developed. Based on the antibody's sequence only, it can predict the hydrophobic interactions of monoclonal antibodies (mAbs). Using the leave-one-out crossvalidation, SSH achieved 91.226% accuracy, 96.396% sensitivity or recall, 84.196% specificity, 87.754% precision, 0.828 Mathew correlation coefficient (MCC), 0.919 f-score, and 0.961 area under the receiver operating characteristic (ROC) curve (AUC).