Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, 750 Republican St, Seattle, WA 98109, United States.
Department of Biology, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, United States.
Bioinformatics. 2023 May 4;39(5). doi: 10.1093/bioinformatics/btad279.
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.
从转录组数据集识别差异表达基因(DEGs)是跨多个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,我们引入了 kimma(混合模型分析中的亲缘关系),这是一个用于灵活的线性混合效应模型的开源 R 包,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 检测到 DEGs 的特异性、敏感性和计算时间与 limma 未配对和 dream 配对模型相似。与其他软件不同,kimma 支持协方差矩阵以及拟合度量,如赤池信息量准则(AIC)。利用遗传亲缘关系的协方差,kimma 揭示了亲缘关系对相关队列中模型拟合和 DEG 检测的影响。因此,kimma 在敏感性、计算时间和模型复杂性方面与当前的 DEG 管道相等或具有竞争力。
Kimma 可在 GitHub 上免费获得 https://github.com/BIGslu/kimma,并在 https://bigslu.github.io/kimma_vignette/kimma_vignette.html 上提供说明性示例。