A combined deep learning framework for mammalian m6A site prediction.

IF 11.1 Q1 CELL BIOLOGY Cell genomics Pub Date : 2024-11-15 DOI:10.1016/j.xgen.2024.100697
Rui Fan, Chunmei Cui, Boming Kang, Zecheng Chang, Guoqing Wang, Qinghua Cui
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Abstract

N6-methyladenosine (m6A) is the most prevalent chemical modification in eukaryotic mRNAs and plays key roles in diverse cellular processes. Precise localization of m6A sites is thus critical for characterizing the functional roles of m6A in various conditions and dissecting the mechanisms governing its deposition. Here, we design a combined framework of Transformer architecture and recurrent neural network, deepSRAMP, to identify m6A sites using sequence-based and genome-derived features. As a result, deepSRAMP achieves a notably enhanced performance compared to its predecessor, SRAMP, the most-used predictor in this field. Moreover, based on multiple benchmark datasets, deepSRAMP greatly outperforms other state-of-the-art m6A predictors, including WHISTLE and DeepPromise, with an average 16.1% and 18.3% increase in AUROC and a 43.9% and 46.4% increase in AUPRC. Finally, deepSRAMP can be successfully exploited on mammalian m6A epitranscriptome mapping under diverse cellular conditions and can potentially reveal differential m6A sites among transcript isoforms of individual genes.

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哺乳动物 m6A 位点预测的深度学习组合框架。
N6-甲基腺苷(m6A)是真核生物 mRNA 中最常见的化学修饰,在多种细胞过程中发挥着关键作用。因此,m6A 位点的精确定位对于鉴定 m6A 在各种条件下的功能作用和剖析其沉积机制至关重要。在这里,我们设计了一个 Transformer 架构和递归神经网络的组合框架--deepSRAMP,利用基于序列和源于基因组的特征来识别 m6A 位点。因此,与该领域最常用的预测器 SRAMP 相比,deepSRAMP 的性能明显提高。此外,基于多个基准数据集,deepSRAMP 的性能大大优于 WHISTLE 和 DeepPromise 等其他最先进的 m6A 预测器,AUROC 平均提高了 16.1% 和 18.3%,AUPRC 平均提高了 43.9% 和 46.4%。最后,deepSRAMP 可以在不同细胞条件下成功用于哺乳动物 m6A 表转录组图谱的绘制,并有可能揭示单个基因转录本异构体中不同的 m6A 位点。
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