1. Computational and Systems Biology
  2. Stem Cells and Regenerative Medicine
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A deep learning algorithm to translate and classify cardiac electrophysiology

  1. Parya Aghasafari Ph.D.
  2. Pei-Chi Yang Ph.D.
  3. Divya C Kernik Ph.D.
  4. Kazuho Sakamoto Ph.D.
  5. Yasunari Kanda Ph.D.
  6. Junko Kurokawa Ph.D
  7. Igor Vorobyov
  8. Colleen E Clancy Ph.D.  Is a corresponding author
  1. University of California Davis, United States
  2. Washington University in St. Louis, United States
  3. University of Shizuoka, Japan
  4. National Institute of Health Sciences, Japan
  5. University California Davis, United States
Research Article
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Cite this article as: eLife 2021;10:e68335 doi: 10.7554/eLife.68335

Abstract

The development of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been a critical in vitro advance in the study of patient-specific physiology, pathophysiology and pharmacology. We designed a new deep learning multitask network approach intended to address the low throughput, high variability and immature phenotype of the iPSC-CM platform. The rationale for combining translation and classification tasks is because the most likely application of the deep learning technology we describe here is to translate iPSC-CMs following application of a perturbation. The deep learning network was trained using simulated action potential (AP) data and applied to classify cells into the drug-free and drugged categories and to predict the impact of electrophysiological perturbation across the continuum of aging from the immature iPSC-CMs to the adult ventricular myocytes. The phase of the AP extremely sensitive to perturbation due to a steep rise of the membrane resistance was found to contain the key information required for successful network multitasking. We also demonstrated successful translation of both experimental and simulated iPSC-CM AP data validating our network by prediction of experimental drug-induced effects on adult cardiomyocyte APs by the latter.

Data availability

Since we used simulated data, we have made all drugged and drug-free iPSC-CM and adult-CM AP data used for training and testing the multitask network publicly available at Clancy lab Github.(https://github.com/ClancyLabUCD/Multitask_network/tree/master/data). In addition, we have illustrated training and test dataset in Figure1 and Figure5.We have also shared the jupyter notebook for preparing clean and organized data for training the network at Clancy lab Github (https://github.com/ClancyLabUCD/Multitask_network/tree/master/jupyter).We also made experimental data used for the model validation publicly available at Clancy lab Github.(https://github.com/ClancyLabUCD/Multitask_network/blob/master/data/clean_data/experiments.csv ). Figure 7 illustrates the experimental data we used to validate the network.

Article and author information

Author details

  1. Parya Aghasafari Ph.D.

    Physiology and Membrane Biology, University of California Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Pei-Chi Yang Ph.D.

    Physiology and Membrane Biology, University of California Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Divya C Kernik Ph.D.

    Biomedical Engineering, Washington University in St. Louis, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kazuho Sakamoto Ph.D.

    Bio-Informational Pharmacology, University of Shizuoka, Shizuoka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Yasunari Kanda Ph.D.

    Division of Pharmacology, National Institute of Health Sciences, Kanagawa, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2527-3526
  6. Junko Kurokawa Ph.D

    Bio-Informational Pharmacology, University of Shizuoka, Shizuoka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Igor Vorobyov

    University California Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4767-5297
  8. Colleen E Clancy Ph.D.

    Physiology and Membrane Biology, University of California Davis, Davis, United States
    For correspondence
    ceclancy@ucdavis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6849-4885

Funding

Common Fund (OT2OD026580)

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

Texas Advanced Computing Center Leadership Resource Allocation (MCB20010)

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

Oracle cloud for research allocation

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

Common Fund (OT2OD025308‐01S2)

  • Parya Aghasafari Ph.D.

American Heart Association (19CDA34770101)

  • Igor Vorobyov

National Heart, Lung, and Blood Institute (R01HL152681)

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

National Heart, Lung, and Blood Institute (R01HL128170)

  • Colleen E Clancy Ph.D.

National Heart, Lung, and Blood Institute (U01HL126273)

  • Colleen E Clancy Ph.D.

Department of Physiology and Membrane Biology Research Partnership Fund

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

Extreme Science and Engineering Discovery Environment (MCB170095)

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

National Center for Supercomputing Applications Blue Waters Broadening Participation Allocation

  • Igor Vorobyov
  • Colleen E Clancy Ph.D.

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

Reviewing Editor

  1. Thomas Hund, The Ohio State University, United States

Publication history

  1. Received: March 11, 2021
  2. Accepted: June 29, 2021
  3. Accepted Manuscript published: July 2, 2021 (version 1)
  4. Version of Record published: July 15, 2021 (version 2)

Copyright

© 2021, Aghasafari 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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