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Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
Journal article   Open access   Peer reviewed

Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data

Sayak Mukherjee, David Stewart, William Stewart, Lewis L Lanier and Jayajit Das
Royal Society Open Science, Vol.4(8), pp.170811-170811
2017
DOI: 10.1098/rsos.170811
PMCID: PMC5579131
PMID: 28879015
url
https://doi.org/10.1098/rsos.170811View
Published (Version of record) Open Access

Abstract

Single-cell responses are shaped by the geometry of signalling kinetic trajectories carved in a multidimensional space spanned by signalling protein abundances. It is, however, challenging to assay a large number (more than 3) of signalling species in live-cell imaging, which makes it difficult to probe single-cell signalling kinetic trajectories in large dimensions. Flow and mass cytometry techniques can measure a large number (4 to more than 40) of signalling species but are unable to track single cells. Thus, cytometry experiments provide detailed time-stamped snapshots of single-cell signalling kinetics. Is it possible to use the time-stamped cytometry data to reconstruct single-cell signalling trajectories? Borrowing concepts of conserved and slow variables from non-equilibrium statistical physics we develop an approach to reconstruct signalling trajectories using snapshot data by creating new variables that remain invariant or vary slowly during the signalling kinetics. We apply this approach to reconstruct trajectories using snapshot data obtained from in silico simulations, live-cell imaging measurements, and, synthetic flow cytometry datasets. The application of invariants and slow variables to reconstruct trajectories provides a radically different way to track objects using snapshot data. The approach is likely to have implications for solving matching problems in a wide range of disciplines.
Biochemistry and Biophysics 1003 1001 trajectory reconstruction flow cytometry mass cytometry pair-matching 1009 single-cell signalling kinetics invariants

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