Supervised dimensionality reduction for exploration of single-cell data by HSS-LDA.

Supervised dimensionality reduction for exploration of single-cell data by HSS-LDA.
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DOI:
10.1016/j.patter.2022.100536
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发表时间:
2022-08-12
期刊:
影响因子:
6.5
通讯作者:
Bendall, Sean C.
Bendall, Sean C.
中科院分区:
其他
文献类型:
--
作者:
Amouzgar, Meelad;Glass, David R.;Baskar, Reema;Averbukh, Inna;Kimmey, Samuel C.;Tsai, Albert G.;Hartmann, Felix J.;Bendall, Sean C.

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Single-cell technologies generate large, high-dimensional datasets encompassing a diversity of omics. Dimensionality reduction captures the structure and heterogeneity of the original dataset, creating low-dimensional visualizations that contribute to the human understanding of data. Existing algorithms are typically unsupervised, using measured features to generate manifolds, disregarding known biological labels such as cell type or experimental time point. We repurpose the classification algorithm, linear discriminant analysis (LDA), for supervised dimensionality reduction of single-cell data. LDA identifies linear combinations of predictors that optimally separate a priori classes, enabling the study of specific aspects of cellular heterogeneity. We implement feature selection by hybrid subset selection (HSS) and demonstrate that this computationally efficient approach generates non-stochastic, interpretable axes amenable to diverse biological processes such as differentiation over time and cell cycle. We benchmark HSS-LDA against several popular dimensionality-reduction algorithms and illustrate its utility and versatility for the exploration of single-cell mass cytometry, transcriptomics, and chromatin accessibility data. LDA is repurposed for supervised dimensionality reduction of single-cell data HSS provides additional feature selection functionality Performance is benchmarked against other dimensionality-reduction methods LDA can be applied to any single-cell omics data Dimensionality reduction enables the visualization of high-dimensional single-cell datasets. Typically, these algorithms are unsupervised, disregarding known biological labels such as cell type or experimental time point. LDA identifies linear combinations of predictors that optimally separate these a priori labels. Combined with HSS for feature selection, LDA generates interpretable axes for visualization and analysis of single-cell data. LDA is extensible to unseen data and can also be used as an input to other methods, for example, to integrate multi-label data for UMAP visualization. LDA enables the exploration of different aspects of cellular heterogeneity, even within the same dataset, by tailoring axes to separate specific, user-defined labels. More generally, this work introduces an alternative approach to visualize single-cell data and highlights the abundance of experimental metadata and cellular features that can be exploited for supervised analysis. Amouzgar et al. repurpose the classification algorithm, LDA, for supervised dimensionality reduction of single-cell data. Paired with HSS for feature selection, LDA creates intuitive visualizations, separating cells from user-defined labels such as experimental time point and cell-cycle phase. LD axes can be extended to unseen data and used as inputs for other algorithms and methods. HSS-LDA is benchmarked against several popular dimensionality-reduction methods and is applied to a diversity of biological problems and single-cell omics.
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