Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data.

Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data.
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DOI:
10.1038/s41467-018-04696-6
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发表时间:
2018-06-22
影响因子:
16.6
通讯作者:
Yau C
Yau C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Campbell KR;Yau C

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Pseudotime algorithms can be employed to extract latent temporal information from cross-sectional data sets allowing dynamic biological processes to be studied in situations where the collection of time series data is challenging or prohibitive. Computational techniques have arisen from single-cell ‘omics and cancer modelling where pseudotime can be used to learn about cellular differentiation or tumour progression. However, methods to date typically implicitly assume homogeneous genetic, phenotypic or environmental backgrounds, which becomes limiting as data sets grow in size and complexity. We describe a novel statistical framework that learns how pseudotime trajectories can be modulated through covariates that encode such factors. We apply this model to both single-cell and bulk gene expression data sets and show that the approach can recover known and novel covariate-pseudotime interaction effects. This hybrid regression-latent variable model framework extends pseudotemporal modelling from its most prevalent area of single cell genomics to wider applications. Cross-sectional omic data often have non-homogeneous genetic, phenotypic, or environmental backgrounds. Here, the authors develop a statistical framework to infer pseudotime trajectories in the presence of such factors as well as their interactions in both single-cell and bulk gene expression analysis
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