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Leveraging online resources to prioritize candidate genes for functional analyses: using the fetal testis as a test case

机译:利用在线资源为功能分析确定候选基因的优先级:使用胎儿睾丸作为测试案例

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摘要

With each new microarray or RNA-seq experiment, massive transcriptomic information is generated with the purpose to produce a list of candidate genes for functional analyses. Yet an effective strategy remains elusive to prioritize the genes on these candidate lists. In this review, we outline a prioritizing strategy by taking a step back from the bench and leveraging the rich range of public databases. This in silico approach provides an economical, less biased, and more effective solution. We discuss the publicly available online resources that can be used to answer a range of questions about a gene. Is the gene of interest is expressed in the system of interest (using expression databases)? Where else is this gene expressed (using added-value transcriptomic resources)? What pathways and processes is the gene involved in (using enriched gene pathway analysis and mouse knockout databases)? Is this gene correlated with human diseases (using human disease variant databases)? Using mouse fetal testis as an example, our strategies identified 298 genes annotated as expressed in the fetal testis. We cross-referenced these genes to existing microarray data and narrowed the list down to cell type specific candidates (35 for Sertoli cells, 11 for Leydig cells, and 25 for germ cells). Our strategies can be customized so that allows researchers to effectively and confidently prioritize genes for functional analysis.
机译:对于每个新的微阵列或RNA-seq实验,都会生成大量的转录组信息,目的是生成功能分析的候选基因列表。然而,要确定这些候选基因的优先顺序,仍然没有有效的策略。在这篇综述中,我们概述了优先策略,方法是从替补席上退后一步,并利用丰富的公共数据库。这种计算机方法可提供一种经济,偏见较少且更有效的解决方案。我们讨论了可用于回答有关基因的一系列问题的公开在线资源。目的基因是否在目的系统中表达(使用表达数据库)?该基因还在哪里表达(使用增值转录组资源)?基因涉及哪些途径和过程(使用丰富的基因途径分析和小鼠基因敲除数据库)?该基因是否与人类疾病相关(使用人类疾病变异数据库)?以小鼠胎儿睾丸为例,我们的策略确定了298个基因,它们被注释为在胎儿睾丸中表达。我们将这些基因交叉引用到现有的微阵列数据中,并将列表缩小到特定细胞类型的候选对象(Sertoli细胞35个,Leydig细胞11个,生殖细胞25个)。我们的策略可以定制,从而使研究人员可以有效而自信地确定基因的功能分析优先级。

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