LAVENDER: latent axes discovery from multiple cytometry samples with non-parametric divergence estimation and multidimensional scaling reconstruction

LAVENDER: latent axes discovery from multiple cytometry samples with non-parametric divergence estimation and multidimensional scaling reconstruction
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LAVENDER:通过非参数散度估计和多维尺度重建从多个细胞计数样本中发现潜轴

DOI:
10.1101/673434
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发表时间:
2019
期刊:
bioRxiv
影响因子:
--
通讯作者:
Yamada Ryo
Yamada Ryo
中科院分区:
--
文献类型:
--
作者:
Nakamura Naotoshi;Okada Daigo;Setoh Kazuya;Kawaguchi Takahisa;Higasa Koichiro;Tabara Yasuharu;Matsuda Fumihiko;Yamada Ryo

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计算细胞术方法现在经常用于流式细胞术和质谱细胞术数据分析。然而,一直缺乏系统的无偏倚方法来评估样本间的变异性,从而阻碍了从大量样本中进行有效的数据挖掘。在这里,我们设计了一种计算方法,称为LAVENDER(从多个细胞计数样本中发现潜在税收,具有非参数化差异估计和多维标度重建)。该算法利用k-近邻密度估计方法测量样本间的Jensen-Shannon距离,并在一个新的坐标空间(LAVENDER空间)中重建样本。然后可以将该空间的轴与其他组学测量进行比较,以获得生物信息。LAVENDER应用于301例季节性流感疫苗免疫的日本个体的多维流式细胞术数据集,揭示了与每个个体的基线免疫学特征相关的轴。该轴与浆细胞的比例和嗜中性粒细胞与淋巴细胞的比例相关,这是全身炎症反应的临床标志物。同样的方法也适用于具有更多分子标记的质谱细胞术数据。这些结果表明,LAVENDER是一个有用的工具,用于识别相似但不同的单细胞数据集之间的关键异质性。
Computational cytometry methods are now frequently used in flow and mass cytometric data analyses. However, systematic bias-free methodologies to assess inter-sample variability have been lacking, thereby hampering efficient data mining from a large set of samples. Here, we devised a computational method termed LAVENDER (latentaxes discovery from multiple cytometry samples withnonparametricdivergenceestimation and multidimensional scalingreconstruction). It measures the Jensen-Shannon distances between samples using thek-nearest neighbor density estimation and reconstructs samples in a new coordinate space, called the LAVENDER space. The axes of this space can then be compared against other omics measurements to obtain biological information. Application of LAVENDER to multidimensional flow cytometry datasets of 301 Japanese individuals immunized with a seasonal influenza vaccine revealed an axis related to baseline immunological characteristics of each individual. This axis correlated with the proportion of plasma cells and the neutrophil-to-lymphocyte ratio, a clinical marker of the systemic inflammatory response. The same method was also applicable to mass cytometry data with more molecular markers. These results demonstrate that LAVENDER is a useful tool for identifying critical heterogeneity among similar, yet different, single-cell datasets.
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