Kimma: flexible linear mixed effects modeling with kinship covariance for RNA-seq data.

Kimma: flexible linear mixed effects modeling with kinship covariance for RNA-seq data.
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DOI:
10.1093/bioinformatics/btad279
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发表时间:
2023-05-04
期刊:
Bioinformatics (Oxford, England)
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从转录组数据集中识别差异表达基因(DEG)是跨学科研究的主要途径。然而,当前的生物信息学工具不支持DEG建模中的协方差矩阵。在这里,我们介绍kimma(混合模型分析中的亲属关系),这是一个开源的R包,用于灵活的线性混合效应建模,包括协变量,权重,随机效应,协方差矩阵和拟合度量。在模拟数据集中,kimma检测DEG具有与limma未配对和梦想配对模型相似的特异性,灵敏度和计算时间。与其他软件不同,kimma支持协方差矩阵以及赤池信息准则(AIC)等拟合度量。利用遗传亲缘关系协方差,Kimma揭示了亲缘关系影响模型拟合和相关队列中的DEG检测。因此,Kimma在灵敏度、计算时间和模型复杂度方面等于或胜过当前的DEG管道。Kimma可在GitHub https://github.com/BIGslu/kimma上免费获取,并在https://bigslu.github.io/kimma_vignette/kimma_vignette.html上提供教学简介。
The identification of differentially expressed genes (DEGs) from transcriptomic datasets is a major avenue of research across diverse disciplines. However, current bioinformatic tools do not support covariance matrices in DEG modeling. Here, we introduce kimma (Kinship In Mixed Model Analysis), an open-source R package for flexible linear mixed effects modeling including covariates, weights, random effects, covariance matrices, and fit metrics. In simulated datasets, kimma detects DEGs with similar specificity, sensitivity, and computational time as limma unpaired and dream paired models. Unlike other software, kimma supports covariance matrices as well as fit metrics like Akaike information criterion (AIC). Utilizing genetic kinship covariance, kimma revealed that kinship impacts model fit and DEG detection in a related cohort. Thus, kimma equals or outcompetes current DEG pipelines in sensitivity, computational time, and model complexity. Kimma is freely available on GitHub https://github.com/BIGslu/kimma with an instructional vignette at https://bigslu.github.io/kimma_vignette/kimma_vignette.html.
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