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Gene Regulatory Networks from Single Cell Data for Exploring Cell Fate Decisions

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Computational Stem Cell Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1975))

Abstract

Single cell experimental techniques now allow us to quantify gene expression in up to thousands of individual cells. These data reveal the changes in transcriptional state that occur as cells progress through development and adopt specialized cell fates. In this chapter we describe in detail how to use our network inference algorithm (PIDC)—and the associated software package NetworkInference.jl—to infer functional interactions between genes from the observed gene expression patterns. We exploit the large sample sizes and inherent variability of single cell data to detect statistical dependencies between genes that indicate putative (co-)regulatory relationships, using multivariate information measures that can capture complex statistical relationships. We provide guidelines on how best to combine this analysis with other complementary methods designed to explore single cell data, and how to interpret the resulting gene regulatory network models to gain insight into the processes regulating cell differentiation.

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Acknowledgements

This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) DTP Studentship to T.E.C., and a BBSRC Future Leaders Fellowship (grant reference BB/N011597/1) to A.C.B. We thank Joe Greener, Gal Horesh, and Ananth Pallaseni for sharing code with us, Suhail Islam for computing support, and Ben MacArthur, Patrick Stumpf, and members of the theoretical systems biology group for useful discussions.

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Authors and Affiliations

  1. Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, UK

    Thalia E. Chan, Michael P. H. Stumpf & Ann C. Babtie

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  1. Thalia E. Chan
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  2. Michael P. H. Stumpf
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  3. Ann C. Babtie
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Correspondence to Ann C. Babtie .

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  1. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Patrick Cahan

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Chan, T.E., Stumpf, M.P.H., Babtie, A.C. (2019). Gene Regulatory Networks from Single Cell Data for Exploring Cell Fate Decisions. In: Cahan, P. (eds) Computational Stem Cell Biology. Methods in Molecular Biology, vol 1975. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9224-9_10

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  • DOI: https://doi.org/10.1007/978-1-4939-9224-9_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9223-2

  • Online ISBN: 978-1-4939-9224-9

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