Interpretable deep learning uncovers cellular properties in label-free live cell images that are predictive of highly metastatic melanoma.


Journal

Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080

Informations de publication

Date de publication:
21 07 2021
Historique:
received: 13 06 2020
revised: 22 01 2021
accepted: 07 05 2021
pubmed: 3 6 2021
medline: 7 4 2022
entrez: 2 6 2021
Statut: ppublish

Résumé

Deep learning has emerged as the technique of choice for identifying hidden patterns in cell imaging data but is often criticized as "black box." Here, we employ a generative neural network in combination with supervised machine learning to classify patient-derived melanoma xenografts as "efficient" or "inefficient" metastatic, validate predictions regarding melanoma cell lines with unknown metastatic efficiency in mouse xenografts, and use the network to generate in silico cell images that amplify the critical predictive cell properties. These exaggerated images unveiled pseudopodial extensions and increased light scattering as hallmark properties of metastatic cells. We validated this interpretation using live cells spontaneously transitioning between states indicative of low and high metastatic efficiency. This study illustrates how the application of artificial intelligence can support the identification of cellular properties that are predictive of complex phenotypes and integrated cell functions but are too subtle to be identified in the raw imagery by a human expert. A record of this paper's transparent peer review process is included in the supplemental information. VIDEO ABSTRACT.

Identifiants

pubmed: 34077708
pii: S2405-4712(21)00158-7
doi: 10.1016/j.cels.2021.05.003
pmc: PMC8353662
mid: NIHMS1711560
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Pagination

733-747.e6

Subventions

Organisme : NCI NIH HHS
ID : K25 CA204526
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM067230
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM136428
Pays : United States

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Assaf Zaritsky (A)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Software and Information Systems Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Electronic address: assafza@bgu.ac.il.

Andrew R Jamieson (AR)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Erik S Welf (ES)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Andres Nevarez (A)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA; Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive, San Diego, La Jolla, CA 92093, USA.

Justin Cillay (J)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Ugur Eskiocak (U)

Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Brandi L Cantarel (BL)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Gaudenz Danuser (G)

Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: gaudenz.danuser@utsouthwestern.edu.

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