论文标题
单细胞贝叶斯反卷积
Single-cell Bayesian deconvolution
论文作者
论文摘要
各个细胞在蛋白质丰度和活性中表现出很大的异质性,这通常反映在荧光标记的报告基因的广泛分布中。由于所有细胞成分在某种程度上都是本质上的荧光,因此观察到的分布包含掩盖细胞种群自然异质性的背景噪声。这限制了我们表征细胞命运决策过程的能力,这些决策过程是发育,免疫反应,组织稳态和许多其他生物学功能的关键的能力。因此,重要的是将贡献与单细胞测量中的信号和噪声区分开。严格解决此问题需要对信号的噪声分布进行反浏览,但是在该方向上的接近仍然有限。在这里,我们提出了一种非参数贝叶斯形式主义,该形式在多维测量中有效地进行了这种反卷积,以允许精确估算置信区间的方式。我们使用该方法研究小鼠胚胎干细胞中肾小管转录因子的表达。
Individual cells exhibit substantial heterogeneity in protein abundance and activity, which is frequently reflected in broad distributions of fluorescently labeled reporters. Since all cellular components are intrinsically fluorescent to some extent, the observed distributions contain background noise that masks the natural heterogeneity of cellular populations. This limits our ability to characterize cell-fate decision processes that are key for development, immune response, tissue homeostasis, and many other biological functions. It is therefore important to separate the contributions from signal and noise in single-cell measurements. Addressing this issue rigorously requires deconvolving the noise distribution from the signal, but approaches in that direction are still limited. Here we present a non-parametric Bayesian formalism that performs such a deconvolution efficiently on multidimensional measurements, in a way that allows estimating confidence intervals precisely. We use the approach to study the expression of the mesodermal transcription factor Brachyury in mouse embryonic stem cells undergoing differentiation.