A protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions.

ABSTRACT: Protein ubiquitination regulates a wide range of cellular processes. The degree of protein ubiquitination is determined by the delicate balance between ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase (DUB)-mediated deubiquitination. In comparison to the E3-substrate interactions, the DUB-substrate interactions (DSIs) remain insufficiently investigated. To address this challenge, we introduce a protein sequence-based ab initio method, TransDSI, which transfers proteome-scale evolutionary information to predict unknown DSIs despite inadequate training datasets. An explainable module is integrated to suggest the critical protein regions for DSIs while predicting DSIs. TransDSI outperforms multiple machine learning strategies against both cross-validation and independent test.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11133436 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature