CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data

Live-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computati...

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Main Authors: Franck Simon, Maria Colomba Comes, Tiziana Tocci, Louise Dupuis, Vincent Cabeli, Nikita Lagrange, Arianna Mencattini, Maria Carla Parrini, Eugenio Martinelli, Herve Isambert
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-01-01
Series:eLife
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Online Access:https://elifesciences.org/articles/95485
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author Franck Simon
Maria Colomba Comes
Tiziana Tocci
Louise Dupuis
Vincent Cabeli
Nikita Lagrange
Arianna Mencattini
Maria Carla Parrini
Eugenio Martinelli
Herve Isambert
author_facet Franck Simon
Maria Colomba Comes
Tiziana Tocci
Louise Dupuis
Vincent Cabeli
Nikita Lagrange
Arianna Mencattini
Maria Carla Parrini
Eugenio Martinelli
Herve Isambert
author_sort Franck Simon
collection DOAJ
description Live-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell–cell interactions in live-cell imaging data. CausalXtract methodology combines network-based and information-based frameworks, which is shown to discover causal effects overlooked by classical Granger and Schreiber causality approaches. We showcase the use of CausalXtract to uncover novel causal effects in a tumor-on-chip cellular ecosystem under therapeutically relevant conditions. In particular, we find that cancer-associated fibroblasts directly inhibit cancer cell apoptosis, independently from anticancer treatment. CausalXtract uncovers also multiple antagonistic effects at different time delays. Hence, CausalXtract provides a unique computational tool to interpret live-cell imaging data for a range of fundamental and translational research applications.
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spelling doaj-art-81f580d13d384a5db373f76f9e8ef1652025-01-17T13:11:19ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.95485CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging dataFranck Simon0https://orcid.org/0000-0002-6952-0819Maria Colomba Comes1Tiziana Tocci2Louise Dupuis3Vincent Cabeli4Nikita Lagrange5Arianna Mencattini6Maria Carla Parrini7https://orcid.org/0000-0002-7082-9792Eugenio Martinelli8Herve Isambert9https://orcid.org/0000-0001-9638-8545CNRS UMR168, Institut Curie, Université PSL, Sorbonne Université, Paris, FranceDepartment of Electronic Engineering, University of Rome Tor Vergata, Rome, ItalyCNRS UMR168, Institut Curie, Université PSL, Sorbonne Université, Paris, France; Department of Electronic Engineering, University of Rome Tor Vergata, Rome, ItalyCNRS UMR168, Institut Curie, Université PSL, Sorbonne Université, Paris, FranceCNRS UMR168, Institut Curie, Université PSL, Sorbonne Université, Paris, FranceCNRS UMR168, Institut Curie, Université PSL, Sorbonne Université, Paris, FranceDepartment of Electronic Engineering, University of Rome Tor Vergata, Rome, ItalyINSERM U830, Institut Curie, Université PSL, Paris, FranceDepartment of Electronic Engineering, University of Rome Tor Vergata, Rome, ItalyCNRS UMR168, Institut Curie, Université PSL, Sorbonne Université, Paris, FranceLive-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell–cell interactions in live-cell imaging data. CausalXtract methodology combines network-based and information-based frameworks, which is shown to discover causal effects overlooked by classical Granger and Schreiber causality approaches. We showcase the use of CausalXtract to uncover novel causal effects in a tumor-on-chip cellular ecosystem under therapeutically relevant conditions. In particular, we find that cancer-associated fibroblasts directly inhibit cancer cell apoptosis, independently from anticancer treatment. CausalXtract uncovers also multiple antagonistic effects at different time delays. Hence, CausalXtract provides a unique computational tool to interpret live-cell imaging data for a range of fundamental and translational research applications.https://elifesciences.org/articles/95485causal inferencetime-lapse image analysislive-cell imagingtumor on chipcausal discoverygranger causality
spellingShingle Franck Simon
Maria Colomba Comes
Tiziana Tocci
Louise Dupuis
Vincent Cabeli
Nikita Lagrange
Arianna Mencattini
Maria Carla Parrini
Eugenio Martinelli
Herve Isambert
CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data
eLife
causal inference
time-lapse image analysis
live-cell imaging
tumor on chip
causal discovery
granger causality
title CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data
title_full CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data
title_fullStr CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data
title_full_unstemmed CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data
title_short CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data
title_sort causalxtract a flexible pipeline to extract causal effects from live cell time lapse imaging data
topic causal inference
time-lapse image analysis
live-cell imaging
tumor on chip
causal discovery
granger causality
url https://elifesciences.org/articles/95485
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