Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.

A better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is an important and fast developing component of...

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Main Authors: Bill Zhao, Kehan Zhang, Christopher S Chen, Emma Lejeune
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-10-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1009443
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author Bill Zhao
Kehan Zhang
Christopher S Chen
Emma Lejeune
author_facet Bill Zhao
Kehan Zhang
Christopher S Chen
Emma Lejeune
author_sort Bill Zhao
collection DOAJ
description A better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is an important and fast developing component of the hiPSC-CM research pipeline. Here we introduce "Sarc-Graph," a computational framework to segment, track, and analyze sarcomeres in fluorescently tagged hiPSC-CMs. Our framework includes functions to segment z-discs and sarcomeres, track z-discs and sarcomeres in beating cells, and perform automated spatiotemporal analysis and data visualization. In addition to reporting good performance for sarcomere segmentation and tracking with little to no parameter tuning and a short runtime, we introduce two novel analysis approaches. First, we construct spatial graphs where z-discs correspond to nodes and sarcomeres correspond to edges. This makes measuring the network distance between each sarcomere (i.e., the number of connecting sarcomeres separating each sarcomere pair) straightforward. Second, we treat tracked and segmented components as fiducial markers and use them to compute the approximate deformation gradient of the entire tracked population. This represents a new quantitative descriptor of hiPSC-CM function. We showcase and validate our approach with both synthetic and experimental movies of beating hiPSC-CMs. By publishing Sarc-Graph, we aim to make automated quantitative analysis of hiPSC-CM behavior more accessible to the broader research community.
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spelling doaj.art-27c7a29ccffb4b8580e6d30fbdc132172022-12-21T19:22:38ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-10-011710e100944310.1371/journal.pcbi.1009443Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.Bill ZhaoKehan ZhangChristopher S ChenEmma LejeuneA better fundamental understanding of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has the potential to advance applications ranging from drug discovery to cardiac repair. Automated quantitative analysis of beating hiPSC-CMs is an important and fast developing component of the hiPSC-CM research pipeline. Here we introduce "Sarc-Graph," a computational framework to segment, track, and analyze sarcomeres in fluorescently tagged hiPSC-CMs. Our framework includes functions to segment z-discs and sarcomeres, track z-discs and sarcomeres in beating cells, and perform automated spatiotemporal analysis and data visualization. In addition to reporting good performance for sarcomere segmentation and tracking with little to no parameter tuning and a short runtime, we introduce two novel analysis approaches. First, we construct spatial graphs where z-discs correspond to nodes and sarcomeres correspond to edges. This makes measuring the network distance between each sarcomere (i.e., the number of connecting sarcomeres separating each sarcomere pair) straightforward. Second, we treat tracked and segmented components as fiducial markers and use them to compute the approximate deformation gradient of the entire tracked population. This represents a new quantitative descriptor of hiPSC-CM function. We showcase and validate our approach with both synthetic and experimental movies of beating hiPSC-CMs. By publishing Sarc-Graph, we aim to make automated quantitative analysis of hiPSC-CM behavior more accessible to the broader research community.https://doi.org/10.1371/journal.pcbi.1009443
spellingShingle Bill Zhao
Kehan Zhang
Christopher S Chen
Emma Lejeune
Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.
PLoS Computational Biology
title Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.
title_full Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.
title_fullStr Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.
title_full_unstemmed Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.
title_short Sarc-Graph: Automated segmentation, tracking, and analysis of sarcomeres in hiPSC-derived cardiomyocytes.
title_sort sarc graph automated segmentation tracking and analysis of sarcomeres in hipsc derived cardiomyocytes
url https://doi.org/10.1371/journal.pcbi.1009443
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AT emmalejeune sarcgraphautomatedsegmentationtrackingandanalysisofsarcomeresinhipscderivedcardiomyocytes