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A procedure to statistically evaluate agreement of differential expression for cross-species genomics

机译:统计评估跨物种基因组差异表达一致性的程序

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摘要

>Motivation: Animal models play a pivotal role in translation biomedical research. The scientific value of an animal model depends on how accurately it mimics the human disease. In principle, microarrays collect the necessary data to evaluate the transcriptomic fidelity of an animal model in terms of the similarity of expression with the human disease. However, statistical methods for this purpose are lacking.>Results: We develop the agreement of differential expression (AGDEX) procedure to measure and determine the statistical significance of the similarity of the results of two experiments that measure differential expression across two groups. AGDEX defines a metric of agreement and determines statistical significance by permutation of each experiment's group labels. Additionally, AGDEX performs a comprehensive permutation-based analysis of differential expression for each experiment, including gene-set analyses and meta-analytic integration of results across studies. As an example, we show how AGDEX was recently used to evaluate the similarity of the transcriptome of a novel model of the brain tumor ependymoma in mice to that of a subtype of the human disease. This result, combined with other observations, helped us to infer the cell of origin of this devastating human cancer.>Availability: An R package is currently available from and will shortly be available from .>Contact: >Supplementary information: are available at Bioinformatics online.
机译:>动机:动物模型在翻译生物医学研究中起着至关重要的作用。动物模型的科学价值取决于它模拟人类疾病的精确程度。原则上,微阵列根据表达与人类疾病的相似性收集必要的数据,以评估动物模型的转录组保真度。但是,缺少用于此目的的统计方法。>结果:我们开发了差异表达协议(AGDEX)程序,用于测量和确定两个测量差异表达的实验结果的相似性的统计显着性跨两个组。 AGDEX定义了一致性指标,并通过排列每个实验的组标签确定统计显着性。此外,AGDEX对每个实验进行差异表达的基于排列的综合分析,包括基因组分析和整个研究结果的荟萃分析整合。例如,我们显示了AGDEX最近如何用于评估小鼠脑肿瘤室管膜瘤的新型模型的转录组与人类疾病亚型的转录组的相似性。该结果与其他观察结果相结合,帮助我们推断出这种毁灭性人类癌症的起源细胞。>可用性: R包目前可从中获得,并且不久将可从中获得。>联系方式: >补充信息:可在线访问生物信息学。

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