OpenAc4C: A gateway to decode the landscape, regulation and pathogenesis of N4-acetylcytidine (ac 4 C) epitranscriptome

Abstract N4-acetylcytidine (ac 4 C) is an ancient and highly conserved chemical marker found in all domains of life. Recent advancements in sequencing techniques have enabled the functional analysis of ac 4 C occurrence by accurately capturing its locations and levels, shedding light on its significant regulatory potential and emerging role in diseases. The OpenAc4C, the first comprehensive knowledgebase exclusively designed for unraveling the ac 4 C epitranscriptome across diverse species, spanning vertebrates, mammals, insects, fungi, plants, bacteria, archaea, and viruses. By mining a large array of ac 4 C epitranscriptome datasets with deep learning-based pipelines, OpenAc4C features a collection of 536,745 ac 4 C sites identified from four distinct next-generation sequencing (NGS)-based techniques, alongside novel insights from Oxford Nanopore direct RNA sequencing (ONT)-based samples, encompassing a total of 33 species. Beyond the ac 4 C landscape, a total of 536,986 ac 4 C-affecting variants were identified in seven species. Among them, 4,766 pathogenic ac 4 C-SNPs may drive ac 4 C dysregulation with implications for disease pathogenesis. In addition, OpenAc4C offers a user-friendly graphical interface and a web-based analysis platform for comprehensive querying and interactive exploration of the database collections. Together, OpenAc4C will serve as a valuable integrated resource to facilitate studies of ac 4 C modification. It is freely accessible at: www.rnamd.org/ac4cportal .