seekCRIT: detecting and characterizing differentially expressed circular RNAs using high-throughput sequencing data

Recently, it has been demonstrated that genomes of many species express single stranded RNAs with covalently closed ends, named circular RNAs. Their regulatory potential and functional relevance are just starting to be revealed. Here we present a novel computational tool, seekCRIT (seek for differentially expressed Circular RNAs In Transcriptome), that identifies circular RNAs and detects their differential expression between two conditions. Using seekCRIT we identified the circular RNAs that are expressed in the neural retina and determined that the majority of them (74%) are expressed in both, ischemic and normal conditions. We identified over 40 circular RNAs that were differentially expressed between both conditions and validated these experimentally using qRT-PCR. The high validation rate of 90% with a false discovery rate (FDR) of < 5% demonstrates the accuracy and reliability of seekCRIT.近年来已有研究证实，诸多物种的基因组可表达具有共价闭合末端的单链RNA，此类分子被命名为环状RNA（circular RNAs）。其调控潜能与功能相关性的研究正逐步得以阐明。本研究开发了一款全新的计算工具seekCRIT（全称：seek for differentially expressed Circular RNAs In Transcriptome，即转录组差异表达环状RNA搜寻工具），该工具可实现环状RNA的识别，并能检测两种实验条件下环状RNA的表达差异。借助seekCRIT，我们鉴定出了在神经视网膜中表达的环状RNA，并发现其中74%的分子可在缺血与正常两种条件下均有表达。我们还鉴定出了40余种在两种条件下存在表达差异的环状RNA，并通过实时定量逆转录聚合酶链反应（qRT-PCR）完成了实验验证。该工具的验证成功率高达90%，且错误发现率（false discovery rate, FDR）小于5%，充分证明了seekCRIT的准确性与可靠性。