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Journal article

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

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-018-04696-6

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Physiology Anatomy and Genetics
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Human Genetics Wt Centre
Role:
Author
ORCID:
0000-0001-7615-8523


More from this funder
Funding agency for:
Yau, C
Grant:
090532/Z/09/Z
More from this funder
Funding agency for:
Yau, C
Campbell, K
Grant:
090532/Z/09/Z
Doctoral studentship


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
9
Issue:
1
Pages:
2442
Publication date:
2017-06-22
Acceptance date:
2018-05-17
DOI:
EISSN:
2041-1723
ISSN:
2041-1723
Pmid:
29934517


Language:
English
Keywords:
Pubs id:
pubs:859940
UUID:
uuid:a3028cfd-376a-4a34-8eab-b0c977d9e657
Local pid:
pubs:859940
Source identifiers:
859940
Deposit date:
2018-09-11

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