Ovando-Vázquez Cesaré, Lepe-Soltero Daniel, Abreu-Goodger Cei
Unidad de Genómica Avanzada (Langebio), Centro de Investigación y de Estudios Avanzados del IPN, Irapuato, Guanajuato, 36821, México.
BMC Genomics. 2016 May 17;17:364. doi: 10.1186/s12864-016-2695-1.
Mammalian genomes encode for thousands of microRNAs, which can potentially regulate the majority of protein-coding genes. They have been implicated in development and disease, leading to great interest in understanding their function, with computational methods being widely used to predict their targets. Most computational methods rely on sequence features, thermodynamics, and conservation filters; essentially scanning the whole transcriptome to predict one set of targets for each microRNA. This has the limitation of not considering that the same microRNA could have different sets of targets, and thus different functions, when expressed in different types of cells.
To address this problem, we combine popular target prediction methods with expression profiles, via machine learning, to produce a new predictor: TargetExpress. Using independent data from microarrays and high-throughput sequencing, we show that TargetExpress outperforms existing methods, and that our predictions are enriched in functions that are coherent with the added expression profile and literature reports.
Our method should be particularly useful for anyone studying the functions and targets of miRNAs in specific tissues or cells. TargetExpress is available at: http://targetexpress.ceiabreulab.org/ .
哺乳动物基因组编码数千种微小RNA,它们可能调控大多数蛋白质编码基因。它们与发育和疾病有关,这引发了人们对了解其功能的浓厚兴趣,计算方法被广泛用于预测其靶标。大多数计算方法依赖于序列特征、热力学和保守性筛选;本质上是扫描整个转录组以预测每个微小RNA的一组靶标。这样做的局限性在于没有考虑到相同的微小RNA在不同类型的细胞中表达时可能具有不同的靶标集,从而具有不同的功能。
为了解决这个问题,我们通过机器学习将流行的靶标预测方法与表达谱相结合,产生了一种新的预测器:TargetExpress。使用来自微阵列和高通量测序的独立数据,我们表明TargetExpress优于现有方法,并且我们的预测在与添加的表达谱和文献报道一致的功能中得到富集。
我们的方法对于任何研究特定组织或细胞中微小RNA功能和靶标的人都应该特别有用。TargetExpress可在以下网址获取:http://targetexpress.ceiabreulab.org/ 。