PT  - JOURNAL ARTICLE
AU  - Max Hebditch
AU  - Jim Warwicker
TI  - Charge and hydrophobicity are key features in sequence-trained machine learning models for predicting the biophysical properties of clinical-stage antibodies
AID  - 10.1101/625830
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 625830
4099  - http://biorxiv.org/content/early/2019/05/02/625830.short
4100  - http://biorxiv.org/content/early/2019/05/02/625830.full
AB  - Improved understanding of properties that mediate protein solubility and resistance to aggregation are important for developing biopharmaceuticals, and more generally in biotechnology and synthetic biology. Recent acquisition of large datasets for antibody biophysical properties enables the search for predictive models. In this report, machine learning methods are used to derive models for 12 biophysical properties. A physicochemical perspective is maintained in analysing the models, leading to the observation that models cluster largely according to charge (cross-interaction measurements) and hydrophobicity (self-interaction methods). These two properties also overlap in some cases, for example in a new interpretation of variation in hydrophobic interaction chromatography. Since the models are developed from differences of antibody variable loops, the next stage is to extend models to more diverse protein sets.Availability The web application for the sequence based algorithms are available on the proteinsol webserver, at https://protein-sol.manchester.ac.uk/abpred, with models and virtualisation software available at https://protein-sol.manchester.ac.uk/software.