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

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...

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Main Authors: Campbell, K, Yau, C
Format: Journal article
Language:English
Published: Nature Publishing Group 2017
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author Campbell, K
Yau, C
author_facet Campbell, K
Yau, C
author_sort Campbell, K
collection OXFORD
description 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.
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spelling oxford-uuid:a3028cfd-376a-4a34-8eab-b0c977d9e6572022-03-27T02:23:50ZUncovering pseudotemporal trajectories with covariates from single cell and bulk expression dataJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a3028cfd-376a-4a34-8eab-b0c977d9e657EnglishSymplectic Elements at OxfordNature Publishing Group2017Campbell, KYau, CPseudotime 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.
spellingShingle Campbell, K
Yau, C
Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
title Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
title_full Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
title_fullStr Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
title_full_unstemmed Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
title_short Uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
title_sort uncovering pseudotemporal trajectories with covariates from single cell and bulk expression data
work_keys_str_mv AT campbellk uncoveringpseudotemporaltrajectorieswithcovariatesfromsinglecellandbulkexpressiondata
AT yauc uncoveringpseudotemporaltrajectorieswithcovariatesfromsinglecellandbulkexpressiondata