Anene Chinedu A, Taggart Emma, Harwood Catherine A, Pennington Daniel J, Wang Jun
Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Centre for Cancer Biology and Therapy, School of Applied Science, London South Bank University, London, United Kingdom.
Front Genet. 2022 Apr 1;13:802838. doi: 10.3389/fgene.2022.802838. eCollection 2022.
The assessment of the cellular heterogeneity and abundance in bulk tissue samples is essential for characterising cellular and organismal states. Computational approaches to estimate cellular abundance from bulk RNA-Seq datasets have variable performances, often requiring benchmarking matrices to select the best performing methods for individual studies. However, such benchmarking investigations are difficult to perform and assess in typical applications because of the absence of gold standard/ground-truth cellular measurements. Here we describe Decosus, an R package that integrates seven methods and signatures for deconvoluting cell types from gene expression profiles (GEP). Benchmark analysis on a range of datasets with ground-truth measurements revealed that our integrated estimates consistently exhibited stable performances across datasets than individual methods and signatures. We further applied Decosus to characterise the immune compartment of skin samples in different settings, confirming the well-established Th1 and Th2 polarisation in psoriasis and atopic dermatitis, respectively. Secondly, we revealed immune system-related UV-induced changes in sun-exposed skin. Furthermore, a significant motivation in the design of Decosus is flexibility and the ability for the user to include new gene signatures, algorithms, and integration methods at run time.
评估大块组织样本中的细胞异质性和丰度对于表征细胞和机体状态至关重要。从大块RNA测序数据集中估计细胞丰度的计算方法具有不同的性能,通常需要基准矩阵来为个别研究选择性能最佳的方法。然而,由于缺乏金标准/真实细胞测量,这种基准调查在典型应用中很难进行和评估。在这里,我们描述了Decosus,一个R包,它集成了七种方法和特征,用于从基因表达谱(GEP)中解卷积细胞类型。对一系列具有真实测量值的数据集进行的基准分析表明,与单个方法和特征相比,我们的综合估计在各个数据集上始终表现出稳定的性能。我们进一步应用Decosus来表征不同环境下皮肤样本的免疫区室,分别证实了银屑病和特应性皮炎中已确立的Th1和Th2极化。其次,我们揭示了免疫系统相关的紫外线诱导的暴露于阳光下皮肤的变化。此外,Decosus设计的一个重要动机是灵活性以及用户在运行时包含新基因特征、算法和整合方法的能力。