Genome-scale deconvolution of RNA structure ensembles

RNA structure heterogeneity is a major challenge when querying RNA structures with chemical probing. We introduce DRACO, an algorithm for the deconvolution of coexisting RNA conformations from mutational profiling experiments. Analysis of the SARS-CoV-2 genome using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and DRACO, identifies multiple regions that fold into two mutually exclusive conformations, including a conserved structural switch in the 3′ untranslated region. This work may open the way to dissecting the heterogeneity of the RNA structurome. DMS-MaPseq利用化学探测技术解析RNA结构时，RNA结构异质性是一项核心挑战。本研究提出DRACO算法，可从突变谱分析实验中解卷积共存的RNA构象。通过硫酸二甲酯突变谱测序（dimethyl sulfate mutational profiling with sequencing, DMS-MaPseq）结合DRACO算法对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）基因组开展分析，鉴定出多个可折叠为两种互斥构象的区域，其中包含3'非翻译区（3' untranslated region）中的保守结构开关。本研究可为解析RNA结构组（RNA structurome）的异质性开辟新路径。DMS-MaPseq