Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data
Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data
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DOI：
10.1101/gr.110189.110
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发表时间：
2011-02-01
期刊：
影响因子：
7
通讯作者：
Gerstein, Mark B.
中科院分区：
文献类型：
--
作者：
Lu, Zhi John;Yip, Kevin Y.;Gerstein, Mark B.
我们提出了一种整合的机器学习方法，incRNA，用于非编码RNA（ncRNA）的全基因组识别。它结合了大量的表达数据，RNA二级结构稳定性，以及蛋白质和核酸水平的进化保守性。使用incRNA模型和来自modENCODE联盟的数据，我们能够分离已知的C。从编码序列和其他基因组元件中以高水平的准确性（在独立验证集上的97%AUC）筛选出了7000多个新的ncRNA候选者，其中1000多个位于C.线虫基因组基于验证集，我们估计约7000个新ncRNA候选物中有91%是真阳性。然后，我们通过RT-PCR分析了15种新的ncRNA候选物，检测了14种的表达。此外，我们描述了所有新的ncRNA候选物的特性，发现它们在发育阶段具有不同的表达模式，并且倾向于使用新的RNA结构家族。我们还发现它们经常被特定的转录因子靶向（类似于59%的基因间新型ncRNA候选物）。总的来说，我们的研究在C.并提供了一种适用于其他生物的方法。
We present an integrative machine learning method, incRNA, for whole-genome identification of noncoding RNAs (ncRNAs). It combines a large amount of expression data, RNA secondary-structure stability, and evolutionary conservation at the protein and nucleic-acid level. Using the incRNA model and data from the modENCODE consortium, we are able to separate known C. elegans ncRNAs from coding sequences and other genomic elements with a high level of accuracy (97% AUC on an independent validation set), and find more than 7000 novel ncRNA candidates, among which more than 1000 are located in the intergenic regions of C. elegans genome. Based on the validation set, we estimate that 91% of the approximately 7000 novel ncRNA candidates are true positives. We then analyze 15 novel ncRNA candidates by RT-PCR, detecting the expression for 14. In addition, we characterize the properties of all the novel ncRNA candidates and find that they have distinct expression patterns across developmental stages and tend to use novel RNA structural families. We also find that they are often targeted by specific transcription factors (similar to 59% of intergenic novel ncRNA candidates). Overall, our study identifies many new potential ncRNAs in C. elegans and provides a method that can be adapted to other organisms.