Institute of Informatics, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland.
Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
Biomed Res Int. 2017;2017:6961786. doi: 10.1155/2017/6961786. Epub 2017 Dec 6.
RNA microarrays and RNA-seq are nowadays standard technologies to study the transcriptional activity of cells. Most studies focus on tracking transcriptional changes caused by specific experimental conditions. Information referring to genes up- and downregulation is evaluated analyzing the behaviour of relatively large population of cells by averaging its properties. However, even assuming perfect sample homogeneity, different subpopulations of cells can exhibit diverse transcriptomic profiles, as they may follow different regulatory/signaling pathways. The purpose of this study is to provide a novel methodological scheme to account for possible internal, functional heterogeneity in homogeneous cell lines, including cancer ones. We propose a novel computational method to infer the proportion between subpopulations of cells that manifest various functional behaviour in a given sample. Our method was validated using two datasets from RNA microarray experiments. Both experiments aimed to examine cell viability in specific experimental conditions. The presented methodology can be easily extended to RNA-seq data as well as other molecular processes. Moreover, it complements standard tools to indicate most important networks from transcriptomic data and in particular could be useful in the analysis of cancer cell lines affected by biologically active compounds or drugs.
RNA 微阵列和 RNA-seq 是当今研究细胞转录活性的标准技术。大多数研究都集中在跟踪特定实验条件引起的转录变化上。通过平均其特性来评估相对大量细胞群体的行为,从而评估涉及基因上调和下调的信息。然而,即使假设样本完全同质,不同的细胞亚群也可能表现出不同的转录组特征,因为它们可能遵循不同的调控/信号通路。本研究的目的是提供一种新的方法学方案,以解释同质细胞系(包括癌细胞)中可能存在的内部功能异质性。我们提出了一种新的计算方法来推断给定样本中表现出各种功能行为的细胞亚群之间的比例。我们的方法使用来自 RNA 微阵列实验的两个数据集进行了验证。这两个实验旨在检查特定实验条件下的细胞活力。所提出的方法可以很容易地扩展到 RNA-seq 数据以及其他分子过程。此外,它补充了标准工具,以指示转录组数据中最重要的网络,特别是在分析受生物活性化合物或药物影响的癌细胞系时可能非常有用。