Elucidation of Genome-wide Understudied Proteins targeted by PROTAC-induced degradation using Interpretable Machine Learning.

ABSTRACT: Proteolysis-targeting chimeras (PROTACs) are hetero-bifunctional molecules. They induce the degradation of a target protein by recruiting an E3 ligase to the target. The PROTAC can inactivate disease-related genes that are considered as understudied, thus has a great potential to be a new type of therapy for the treatment of incurable diseases. However, only hundreds of proteins have been experimentally tested if they are amenable to the PROTACs. It remains elusive what other proteins can be targeted by the PROTAC in the entire human genome. For the first time, we have developed an interpretable machine learning model PrePROTAC, which is based on a transformer-based protein sequence descriptor and random forest classification to predict genome-wide PROTAC-induced targets degradable by CRBN

SUBMITTER: Xie L 

PROVIDER: S-EPMC9980153 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature