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Synthesising Executable Gene Regulatory Networks from Single-Cell Gene Expression Data

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conference contribution
posted on 2015-05-26, 11:29 authored by J. Fisher, A. S. Köksal, Nir Piterman, S. Woodhouse
Recent experimental advances in biology allow researchers to obtain gene expression profiles at single-cell resolution over hundreds, or even thousands of cells at once. These single-cell measurements provide snapshots of the states of the cells that make up a tissue, instead of the population-level averages provided by conventional high-throughput experiments. This new data therefore provides an exciting opportunity for computational modelling. In this paper we introduce the idea of viewing single-cell gene expression profiles as states of an asynchronous Boolean network, and frame model inference as the problem of reconstructing a Boolean network from its state space. We then give a scalable algorithm to solve this synthesis problem. We apply our technique to both simulated and real data. We first apply our technique to data simulated from a well established model of common myeloid progenitor differentiation. We show that our technique is able to recover the original Boolean network rules. We then apply our technique to a large dataset taken dur- ing embryonic development containing thousands of cell measurements. Our technique synthesises matching Boolean networks, and analysis of these models yields new predictions about blood development which our experimental collaborators were able to verify.

History

Citation

Computer Aided Verification 2015, Part I, Lecture Notes in Computer Science 9206, pp. 544–560, 2015

Author affiliation

/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of Computer Science

Source

Computer Aided Verification, San Francisco, CA, USA

Version

  • AM (Accepted Manuscript)

Published in

Computer Aided Verification 2015

Publisher

Springer-Verlag

issn

0302-9743

isbn

978-3-319-21689-8;978-3-319-21690-4

Copyright date

1007

Available date

2016-07-16

Publisher version

http://link.springer.com/chapter/10.1007/978-3-319-21690-4_38

Temporal coverage: start date

2015-07-18

Temporal coverage: end date

2015-07-24

Language

en

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