School of Life Sciences, Center for Synthetic and Systems Biology, Ministry of Education Key Laboratory of Bioinformatics, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, P.R. China.
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.
Int J Oncol. 2017 Dec;51(6):1625-1638. doi: 10.3892/ijo.2017.4162. Epub 2017 Oct 16.
Circular RNAs (circRNAs) are pervasively expressed circles of non‑coding RNAs. Even though many circRNAs have been reported in humans, their expression patterns and functions remain poorly understood. In this study, we employed a pipeline named RAISE to detect circRNAs in RNA‑seq data. RAISE can fully characterize circRNA structure and abundance. We evaluated inter-individual variations in circRNA expression in humans by applying this pipeline to numerous non‑poly(A)-selected RNA‑seq data. We identified 59,128 circRNA candidates in 61 human liver samples, with almost no overlap in the circRNA of the recruited samples. Approximately 89% of the circRNAs were detected in one or two samples. In comparison, 10% of the linear mRNAs and non‑coding RNAs were detected in each sample. We estimated the variation in other tissues, especially the circRNA high-abundance tissues, in advance. Only 0.5% of the 50,631 brain circRNA candidates were shared among the 30 recruited brain samples, which is similar to the proportion in liver. Moreover, we found inter- and intra-individual diversity in circRNAs expression in the granulocyte RNA‑seq data from seven individuals sampled 3 times at one-month intervals. Our findings suggest that careful consideration of inter-individual diversity is required when extensively identifying human circRNAs or proposing their use as potential biomarkers and therapeutic targets in disease.
环状 RNA（circRNAs）是广泛表达的非编码 RNA 环。尽管已经在人类中报道了许多 circRNAs，但它们的表达模式和功能仍知之甚少。在这项研究中，我们采用了一种名为 RAISE 的管道来检测 RNA-seq 数据中的 circRNAs。RAISE 可以全面描述 circRNA 的结构和丰度。我们通过将该管道应用于众多非多聚（A）选择的 RNA-seq 数据，评估了人类中 circRNA 表达的个体间差异。我们在 61 个人类肝脏样本中鉴定了 59,128 个 circRNA 候选物，招募样本中的 circRNA 几乎没有重叠。大约 89%的 circRNAs 在一个或两个样本中被检测到。相比之下，每个样本中检测到的线性 mRNA 和非编码 RNA 约为 10%。我们提前估计了其他组织（特别是 circRNA 高丰度组织）的变化。在 30 个招募的脑样本中，只有 50,631 个脑 circRNA 候选物中的 0.5%是共享的，与肝脏中的比例相似。此外，我们在从七个个体中采样的粒细胞 RNA-seq 数据中发现了 circRNAs 表达的个体内和个体间多样性，这些个体在一个月的间隔内采样了 3 次。我们的研究结果表明，在广泛鉴定人类 circRNAs 或提出将其用作疾病潜在生物标志物和治疗靶点时，需要仔细考虑个体间的多样性。
