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

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 p...

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Main Authors: Sayak Mukherjee, David Stewart, William Stewart, Lewis L. Lanier, Jayajit Das
Format: Article
Language:English
Published: The Royal Society 2017-01-01
Series:Royal Society Open Science
Subjects:
Online Access:https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.170811
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author Sayak Mukherjee
David Stewart
William Stewart
Lewis L. Lanier
Jayajit Das
author_facet Sayak Mukherjee
David Stewart
William Stewart
Lewis L. Lanier
Jayajit Das
author_sort Sayak Mukherjee
collection DOAJ
description 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.
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spelling doaj.art-13a691768d794e15a7a2d347fb63ab672022-12-21T20:37:07ZengThe Royal SocietyRoyal Society Open Science2054-57032017-01-014810.1098/rsos.170811170811Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped dataSayak MukherjeeDavid StewartWilliam StewartLewis L. LanierJayajit DasSingle-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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.170811single-cell signalling kineticsflow cytometrymass cytometrytrajectory reconstructioninvariantspair-matching
spellingShingle Sayak Mukherjee
David Stewart
William Stewart
Lewis L. Lanier
Jayajit Das
Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
Royal Society Open Science
single-cell signalling kinetics
flow cytometry
mass cytometry
trajectory reconstruction
invariants
pair-matching
title Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
title_full Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
title_fullStr Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
title_full_unstemmed Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
title_short Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data
title_sort connecting the dots across time reconstruction of single cell signalling trajectories using time stamped data
topic single-cell signalling kinetics
flow cytometry
mass cytometry
trajectory reconstruction
invariants
pair-matching
url https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.170811
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