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Biology subjects

Chua, Z. M.

Publications and source records attributed to Chua, Z. M..

2 recordsLinked to original sources

PROTGOAT : Improved automated protein function predictions using Protein Language Models

Accurate prediction of protein function is crucial for understanding biological processes and various disease mechanisms. Current methods for protein function prediction relies primarily on sequence similarities and often misses out on important aspects of protein function. New developments in protein function prediction methods have recently shown exciting progress via the use of large transformer-based Protein Language Models (PLMs) that allow for the capture of nuanced relationships between amino acids in protein sequences which are crucial for understanding their function. This has enabled an unprecedented level of accuracy in predicting the functions of previously little understood proteins. We here developed an ensemble method called PROTGOAT based on embeddings extracted from multiple and diverse pre-trained PLMs and existing text information about the protein in published literature. PROTGOAT outperforms most current state-of-the-art methods, ranking fourth in the Critical Assessment of Functional Annotation (CAFA 5), a global competition benchmarking such developments among 1600 methods tested. The high performance of our method demonstrates how protein function prediction can be improved through the use of an ensemble of diverse PLMs. PROTGOAT is publicly available for academic use and can be accessed here: https://github.com/zongmingchua/cafa5

bioinformatics↗

Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence and aging.

Cellular senescence, a stress-induced stable proliferation arrest associated with an inflammatory Senescence-Associated Secretory Phenotype (SASP), is a cause of aging. In senescent cells, Cytoplasmic Chromatin Fragments (CCFs) activate SASP via the anti-viral cGAS/STING pathway. PML protein organizes PML nuclear bodies (NBs), also involved in senescence and anti-viral immunity. The HIRA histone H3.3 chaperone localizes to PML NBs in senescent cells. Here, we show that HIRA and PML are essential for SASP expression, tightly linked to HIRAs localization to PML NBs. Inactivation of HIRA does not directly block expression of NF-{kappa}B target genes. Instead, an H3.3-independent HIRA function activates SASP through a CCF-cGAS-STING-TBK1-NF-{kappa}B pathway. HIRA physically interacts with p62/SQSTM1, an autophagy regulator and negative SASP regulator. HIRA and p62 co-localize in PML NBs, linked to their antagonistic regulation of SASP, with PML NBs controlling their spatial configuration. These results outline a role for HIRA and PML in regulation of SASP.

cell biology↗