1. Cell Biology
  2. Computational and Systems Biology
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Deciphering anomalous heterogeneous intracellular transport with neural networks

Research Article
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Cite this article as: eLife 2020;9:e52224 doi: 10.7554/eLife.52224

Abstract

Intracellular transport is predominantly heterogeneous in both time and space, exhibiting varying non-Brownian behavior. Characterization of this movement through averaging methods over an ensemble of trajectories or over the course of a single trajectory often fails to capture this heterogeneity. Here, we developed a deep learning feedforward neural network trained on fractional Brownian motion, providing a novel, accurate and efficient method for resolving heterogeneous behavior of intracellular transport in space and time. The neural network requires significantly fewer data points compared to established methods. This enables robust estimation of Hurst exponents for very short time series data, making possible direct, dynamic segmentation and analysis of experimental tracks of rapidly moving cellular structures such as endosomes and lysosomes. By using this analysis, fractional Brownian motion with a stochastic Hurst exponent was used to interpret, for the first time, anomalous intracellular dynamics, revealing unexpected differences in behavior between closely related endocytic organelles.

Article and author information

Author details

  1. Daniel Han

    Department of Mathematics, School of Biological Sciences, Department of Physics and Astronomy, University of Manchester, Manchester, United Kingdom
    For correspondence
    daniel.han@manchester.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9088-1651
  2. Nickolay Korabel

    Mathematics, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Runze Chen

    Department of Computer Science, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark Johnston

    School of Biological Sciences, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Anna Gavrilova

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Victoria J Allan

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    For correspondence
    viki.allan@manchester.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4583-0836
  7. Sergei Fedotov

    Department of Mathematics, University of Manchester, Manchester, United Kingdom
    For correspondence
    sergei.fedotov@manchester.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  8. Thomas A Waigh

    Physics and Astronomy, University of Manchester, Manchester, United Kingdom
    For correspondence
    t.a.waigh@manchester.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7084-559X

Funding

Wellcome Trust (215189/Z/19/Z)

  • Daniel Han

EPSRC (EP/J019526/1)

  • Nickolay Korabel
  • Victoria J Allan
  • Sergei Fedotov
  • Thomas A Waigh

BBSRC (BB/H017828/1)

  • Victoria J Allan

Wellcome Trust (108867/Z/15/Z)

  • Anna Gavrilova

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Robert H Singer, Albert Einstein College of Medicine, United States

Publication history

  1. Received: September 26, 2019
  2. Accepted: March 22, 2020
  3. Accepted Manuscript published: March 24, 2020 (version 1)
  4. Version of Record published: April 8, 2020 (version 2)
  5. Version of Record updated: May 26, 2020 (version 3)

Copyright

© 2020, Han et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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