Deciphering the functional landscape of phosphosites with deep neural network

Autor: Zhongjie Liang, Tonghai Liu, Qi Li, Guangyu Zhang, Bei Zhang, Xikun Du, Jingqiu Liu, Zhifeng Chen, Hong Ding, Guang Hu, Hao Lin, Fei Zhu, Cheng Luo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 9, Pp 113048- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.113048
Popis: Summary: Current biochemical approaches have only identified the most well-characterized kinases for a tiny fraction of the phosphoproteome, and the functional assignments of phosphosites are almost negligible. Herein, we analyze the substrate preference catalyzed by a specific kinase and present a novel integrated deep neural network model named FuncPhos-SEQ for functional assignment of human proteome-level phosphosites. FuncPhos-SEQ incorporates phosphosite motif information from a protein sequence using multiple convolutional neural network (CNN) channels and network features from protein-protein interactions (PPIs) using network embedding and deep neural network (DNN) channels. These concatenated features are jointly fed into a heterogeneous feature network to prioritize functional phosphosites. Combined with a series of in vitro and cellular biochemical assays, we confirm that NADK-S48/50 phosphorylation could activate its enzymatic activity. In addition, ERK1/2 are discovered as the primary kinases responsible for NADK-S48/50 phosphorylation. Moreover, FuncPhos-SEQ is developed as an online server.
Databáze: Directory of Open Access Journals