Comparisons of isomiR patterns and classification performance using the rank-based MANOVA and 10-fold cross-validation
Comparisons of isomiR patterns and classification performance using the rank-based MANOVA and 10-fold cross-validation
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使用基于排序的多元方差分析和 10 倍交叉验证比较 isomiR 模式和分类性能
DOI：
10.1016/j.gene.2014.11.026
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Chen Feng
中科院分区：
文献类型：
--
作者：
Zhang Hui;Yang Sheng;Guo Li;Zhao Yang;Shao Fang;Chen Feng
下一代测序技术已经鉴定出一系列可能与癌症进展相关的miRNA变体（称为“isomiRs”）。我们提供了一种新的策略，通过isomiR谱的视图来重新分析miR-seq数据集。首先，使用基于负二项分布的DESeq算法检测差异表达（DE）isomiR。其次，采用基于秩次的MANOVA分析比较正常组织和肿瘤组织的isomiR模式。此外，对逻辑回归、k-近邻和随机森林三种特征的分类性能进行了全面的研究。最后，功能富集分析与特定isomiRs的推定目标，以阐明其生物学功能。此外，将该方法应用于从TCGA下载的乳腺浸润性癌的miR-seq数据集。我们发现，来自同一个miRNA位点的多个isomiRs的表达水平在正常和肿瘤样本之间显示出显著的不一致性。在大多数情况下，多个DE isomiR的logistic回归上级其他回归，AUC最高，AIC最低。类似地，DE isomiRs在标准分类器的平均准确度方面表现最好。整合靶点在一些癌症相关通路中显著富集，包括MAPK信号通路和粘着斑。总体而言，我们可以推荐基于秩的MANOVA来比较不同的isomiR模式，并且在miRNA测序研究中需要考虑对isomiR的进一步研究。
Next generation sequencing technology has identified a series of miRNA variants (named “isomiRs”), which might be associated with cancer progression. We provide a new strategy to reanalyze the miR-seq datasets through a view of the isomiR spectrum. Firstly, differentially expressed (DE) isomiRs were detected with the DESeq algorithm based on negative binomial distribution. Secondly, the rank-based MANOVA was adopted to compare the isomiR patterns between normal and tumor tissues. Moreover, a comprehensive survey on classification performance of three features was conducted, including the logistic regression,k-nearest neighbors and Random Forest. Finally, functional enrichment analysis was performed with the putative targets of specific isomiRs to elucidate their biological functions. Furthermore, the methods were applied to the downloaded miR-seq datasets of breast invasive carcinoma from TCGA. We found that the expression levels of multiple isomiRs derived from the same miRNA locus showed significant inconsistency between normal and tumor samples. In most cases, logistic regression with multiple DE isomiRs was superior to the others, with highest AUC and lowest AIC. Similarly, DE isomiRs performed best in the average accuracy of standard classifiers. Integrated targets were significantly enriched in some cancer-related pathways, including MAPK signaling pathway, and focal adhesion. Collectively, we could recommend the rank-based MANOVA for comparing different isomiR patterns, and further investigation on isomiRs needs to be considered in miRNA sequencing research.