INTEGRATE-Circ and INTEGRATE-Vis: unbiased detection and visualization of fusion-derived circular RNA.
INTEGRATE-Circ and INTEGRATE-Vis: unbiased detection and visualization of fusion-derived circular RNA.
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DOI：
10.1093/bioinformatics/btad569
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发表时间：
2023-09-02
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影响因子：
--
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--
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RNA的反向剪接导致环状而不是线性转录物，称为环状RNA（circRNA）。最近发现的且知之甚少的由多个基因组成的circRNA子集，称为融合衍生的环状RNA（fcircRNA），代表了一类显示具有致癌潜力的潜在生物标志物。fcircRNA的检测避开了现有的分析工具，使得难以更全面地评估其流行程度和功能。改进的检测方法可能会导致与fcircRNA相关的其他生物学和临床见解。我们开发了第一个用于检测fcircRNA（INTEGRATE-Circ）和从RNA-Seq数据可视化fcircRNA（INTEGRATE-Vis）的无偏工具。基于我们对模拟RNA-Seq数据的分析，我们发现INTEGRATE-Circ比其他工具更灵敏、精确和准确，并且我们的工具在分析公共淋巴母细胞系数据时能够优于其他工具。最后，我们能够在体外验证在充分表征的乳腺癌细胞系中通过INTEGRATE-Circ检测到的三种新型fcircRNA。INTEGRATE-Circ和INTEGRATE-Vis的开源代码可在https://www.github.com/ChrisMaherLab/INTEGRATE-CIRC和https://www.github.com/ChrisMaherLab/INTEGRATE-Vis上获得。
Backsplicing of RNA results in circularized rather than linear transcripts, known as circular RNA (circRNA). A recently discovered and poorly understood subset of circRNAs that are composed of multiple genes, termed fusion-derived circular RNAs (fcircRNAs), represent a class of potential biomarkers shown to have oncogenic potential. Detection of fcircRNAs eludes existing analytical tools, making it difficult to more comprehensively assess their prevalence and function. Improved detection methods may lead to additional biological and clinical insights related to fcircRNAs. We developed the first unbiased tool for detecting fcircRNAs (INTEGRATE-Circ) and visualizing fcircRNAs (INTEGRATE-Vis) from RNA-Seq data. We found that INTEGRATE-Circ was more sensitive, precise and accurate than other tools based on our analysis of simulated RNA-Seq data and our tool was able to outperform other tools in an analysis of public lymphoblast cell line data. Finally, we were able to validate in vitro three novel fcircRNAs detected by INTEGRATE-Circ in a well-characterized breast cancer cell line. Open source code for INTEGRATE-Circ and INTEGRATE-Vis is available at https://www.github.com/ChrisMaherLab/INTEGRATE-CIRC and https://www.github.com/ChrisMaherLab/INTEGRATE-Vis.
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4.6
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4.1
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