Mueller Jonas, Jaakkola Tommi, Gifford David
MIT Computer Science & Artificial Intelligence Laboratory Cambridge, MA 02139.
J Am Stat Assoc. 2018;113(523):1296-1310. doi: 10.1080/01621459.2017.1341412. Epub 2018 Jun 12.
We present a nonparametric framework to model a short sequence of probability distributions that vary both due to underlying effects of sequential progression and confounding noise. To distinguish between these two types of variation and estimate the sequential-progression effects, our approach leverages an assumption that these effects follow a persistent trend. This work is motivated by the recent rise of single-cell RNA-sequencing experiments over a brief time course, which aim to identify genes relevant to the progression of a particular biological process across diverse cell populations. While classical statistical tools focus on scalar-response regression or order-agnostic differences between distributions, it is desirable in this setting to consider both the full distributions as well as the structure imposed by their ordering. We introduce a new regression model for ordinal covariates where responses are univariate distributions and the underlying relationship reflects consistent changes in the distributions over increasing levels of the covariate. This concept is formalized as a in distributions, which we define as an evolution that is linear under the Wasserstein metric. Implemented via a fast alternating projections algorithm, our method exhibits numerous strengths in simulations and analyses of single-cell gene expression data.
我们提出了一个非参数框架,用于对因序列进展的潜在效应和混杂噪声而变化的短序列概率分布进行建模。为了区分这两种类型的变化并估计序列进展效应,我们的方法利用了这些效应遵循持续趋势的假设。这项工作的动机来自于近期在短时间内单细胞RNA测序实验的兴起,这些实验旨在识别与跨不同细胞群体的特定生物学过程进展相关的基因。虽然经典统计工具侧重于标量响应回归或分布之间的顺序无关差异,但在这种情况下,考虑完整分布及其排序所施加的结构是很有必要的。我们引入了一种用于有序协变量的新回归模型,其中响应是单变量分布,潜在关系反映了随着协变量水平增加分布的一致变化。这个概念在分布中被形式化为一个,我们将其定义为在瓦瑟斯坦度量下是线性的演化。通过快速交替投影算法实现,我们的方法在单细胞基因表达数据的模拟和分析中展现出诸多优势。