Accurate detection of m6A RNA modifications in native RNA sequences
Accurate detection of m6A RNA modifications in native RNA sequences
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DOI：
10.1038/s41467-019-11713-9
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发表时间：
2019-09-09
影响因子：
16.6
通讯作者：
Novoa, Eva Maria
中科院分区：
文献类型：
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作者：
Liu, Huanle;Begik, Oguzhan;Novoa, Eva Maria
在过去的几年中，epitranscriptomics领域已经经历了巨大的扩张，然而，一个主要的限制是缺乏通用的方法来映射RNA修饰转录组范围。在这里，我们表明，使用直接RNA测序，N-6-甲基腺苷（m（6）A）RNA修饰可以检测到高精度，在系统误差和碱基识别质量下降的形式。具体来说，我们发现我们的算法，用m（6）A修饰和未修饰的合成序列训练，可以预测m（6）A RNA修饰，准确率接近90%。然后，我们将我们的发现扩展到酵母数据集，发现我们的方法可以识别体内m（6）A RNA修饰，准确率为87%。此外，我们进一步验证了我们的方法，表明这些“错误”通常不会在酵母ime 4敲除菌株中观察到，缺乏m（6）A修饰。我们的研究结果开辟了途径，以调查RNA修饰在其天然RNA背景下的生物学作用。
The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct RNA sequencing, N-6-methyladenosine (m(6)A) RNA modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Specifically, we find that our algorithm, trained with m(6)A-modified and unmodified synthetic sequences, can predict m(6)A RNA modifications with similar to 90% accuracy. We then extend our findings to yeast data sets, finding that our method can identify m(6)A RNA modifications in vivo with an accuracy of 87%. Moreover, we further validate our method by showing that these 'errors' are typically not observed in yeast ime4-knockout strains, which lack m(6)A modifications. Our results open avenues to investigate the biological roles of RNA modifications in their native RNA context.