Probabilistic thermal stability prediction through sparsity promoting transformer representation

Yevgen Zainchkovskyy, Jesper Ferkinghoff-Borg, Anja Bennett, Thomas Egebjerg, Nikolai Lorenzen, Per Jr. Greisen, Søren Hauberg, Carsten Stahlhut

Keywords: Protein Melting Temperature, Transformer Models, Embeddings, Gaussian Processes, Regression, Sparsity promotion

TL;DR: Improvement of mean-pooling of pre-trained transformer's latent representations by learning a mask.

Abstract: Pre-trained protein language models have demonstrated significant applicability in different protein engineering task. A general usage of these pre-trained transformer models latent representation is to use a mean pool across residue positions to reduce the feature dimensions to further downstream tasks such as predicting bio-physics properties or other functional behaviours. In this paper we provide a two-fold contribution to machine learning (ML) driven drug design. Firstly, we demonstrate the power of sparsity by promoting penalization of pre- trained transformer models to secure more robust and accurate melting temperature (Tm) prediction of single-chain variable fragments with a mean absolute error of 0.23C. Secondly, we demonstrate the power of framing our prediction problem in a probabilistic framework. Specifically, we advocate for the need of adopting probabilistic frameworks especially in the context of ML driven drug design.