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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of differential translation in genome wide studies
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Identification of differential translation in genome wide studies

机译：在全基因组研究中鉴定差异翻译

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摘要

Regulation of gene expression through translational control is a fundamental mechanism implicated in many biological processes ranging from memory formation to innate immunity and whose dysregulation contributes to human diseases. Genome wide analyses of translational control strive to identify differential translation independent of cytosolic mRNA levels. For this reason, most studies measure genes' translation levels as log ratios (translation levels divided by corresponding cytosolic mRNA levels obtained in parallel). Counterintuitively, arising from a mathematical necessity, these log ratios tend to be highly correlated with the cytosolic mRNA levels. Accordingly, they do not effectively correct for cytosolic mRNA level and generate substantial numbers of biological false positives and false negatives. We show that analysis of partial variance, which produces estimates of translational activity that are independent of cytosolic mRNA levels, is a superior alternative. When combined with a variance shrinkage method for estimating error variance, analysis of partial variance has the additional benefit of having greater statistical power and identifying fewer genes as translationally regulated resulting merely from unrealistically low variance estimates rather than from large changes in translational activity. In contrast to log ratios, this formal analytical approach estimates translation effects in a statistically rigorous manner, eliminates the need for inefficient and error-prone heuristics, and produces results that agree with biological function. The method is applicable to datasets obtained from both the commonly used polysome microarray method and the sequencing-based ribosome profiling method.
机译：通过翻译控制调节基因表达是从记忆形成到先天免疫的许多生物学过程都涉及的基本机制，其失调会导致人类疾病。全基因组翻译控制分析力图确定与细胞质mRNA水平无关的差异翻译。因此，大多数研究将基因的翻译水平测量为对数比（翻译水平除以并行获得的相应胞质mRNA水平）。违反直觉地，由于数学上的必要性，这些对数比倾向于与胞质mRNA水平高度相关。因此，它们不能有效地校正胞质mRNA水平，并且产生大量的生物学假阳性和假阴性。我们表明，对部分方差的分析（产生独立于胞质mRNA水平的翻译活性的估计值）是一种更好的选择。当与方差收缩方法结合以估计误差方差时，部分方差分析的额外好处是具有更大的统计能力，并且仅由于不切实际的低方差估计而不是由翻译活动的较大变化而识别出较少的基因受翻译调控。与对数比相反，这种形式化的分析方法以统计上严格的方式估算翻译效果，消除了对低效且容易出错的启发式方法的需求，并产生了与生物学功能相符的结果。该方法适用于从常用的多核糖体微阵列方法和基于测序的核糖体谱分析方法获得的数据集。

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