N4-acetylcytidine (ac4C) is a crucial post-transcriptional modification in human mRNA, involving the acetylation of the nitrogen atom at the fourth position of cytidine. This modification, catalyzed by N-acetyltransferases such as NAT10, is primarily found in mRNA's coding regions and enhances translation efficiency and mRNA stability. ac4C is closely associated with various diseases, including cancer. Therefore, accurately identifying ac4C in human mRNA is essential for gaining deeper insights into disease pathogenesis and provides potential pathways for the development of novel medical interventions. In silico methods for identifying ac4C are gaining increasing attention due to their cost-effectiveness, requiring minimal human and material resources. In this study, we propose an efficient and accurate computational framework, Caps-ac4C, for the precise detection of ac4C in human mRNA. Caps-ac4C utilizes chaos game representation to encode RNA sequences into "images" and employs capsule networks to learn global and local features from these RNA "images". Experimental results demonstrate that Caps-ac4C achieves state-of-the-art performance, achieving 95.47% accuracy and 0.912 MCC on the test set, surpassing the current best methods by 10.69% accuracy and 0.216 MCC. In summary, Caps-ac4C represents the most accurate tool for predicting ac4C sites in human mRNA, highlighting its significant contribution to RNA modification research. For user convenience, we developed a user-friendly web server, which can be accessed for free at:https://awi.cuhk.edu.cn/Caps-ac4C/index.php.
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http://dx.doi.org/10.1016/j.jmb.2025.168961 | DOI Listing |
Microb Cell Fact
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Department of Laboratory Medicine, The Seventh Affiliated Hospital of Southern Medical University, Foshan, Guangdong, 528244, China.
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Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory of Coal Environmental Pathogenicity and Prevention (Ministry of Education, China, Shanxi Medical University, No. 56, Xinjian South Road, Yingze District, Taiyuan City, 030000, Shanxi Province, China.
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Department of Pharmacotherapy and Translational Research, College of Pharmacy, Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, Florida. Electronic address:
Many factors cause interperson variability in the activity and expression of the cytochrome P450 (CYP) drug-metabolizing enzymes in the liver, leading to variable drug exposure and treatment outcomes. Several liver-enriched transcription factors are associated with CYP expression, with estrogen receptor α (ESR1) and constitutive androstane receptor (CAR or NR1I3) being the 2 top factors. ESR1 and NR1I3 undergo extensive alternative splicing that results in numerous splice isoforms, but how these splice isoforms associate with CYP expression is unknown.
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Javelin Biotech, Inc, Woburn, Massachusetts. Electronic address:
Polypharmacy-related drug-drug interactions (DDIs) are a significant and growing healthcare concern. An increasing number of therapeutic drugs on the market underscores the necessity to accurately assess new drug combinations during preclinical evaluation for DDIs. In vitro primary human hepatocytes (PHH) models are only applicable for short-term induction studies because of their rapid loss of metabolic function.
View Article and Find Full Text PDFJ Mol Biol
January 2025
Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan. Electronic address:
N4-acetylcytidine (ac4C) is a crucial post-transcriptional modification in human mRNA, involving the acetylation of the nitrogen atom at the fourth position of cytidine. This modification, catalyzed by N-acetyltransferases such as NAT10, is primarily found in mRNA's coding regions and enhances translation efficiency and mRNA stability. ac4C is closely associated with various diseases, including cancer.
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