Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd

Abstract Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi‐signaling networks across cells and cell types, with important implications to understand and treat diseases such a...

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Main Authors: Attila Gabor, Marco Tognetti, Alice Driessen, Jovan Tanevski, Baosen Guo, Wencai Cao, He Shen, Thomas Yu, Verena Chung, Single Cell Signaling in Breast Cancer DREAM Consortium members, Bernd Bodenmiller, Julio Saez‐Rodriguez
Format: Article
Language:English
Published: Springer Nature 2021-10-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.15252/msb.202110402
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author Attila Gabor
Marco Tognetti
Alice Driessen
Jovan Tanevski
Baosen Guo
Wencai Cao
He Shen
Thomas Yu
Verena Chung
Single Cell Signaling in Breast Cancer DREAM Consortium members
Bernd Bodenmiller
Julio Saez‐Rodriguez
author_facet Attila Gabor
Marco Tognetti
Alice Driessen
Jovan Tanevski
Baosen Guo
Wencai Cao
He Shen
Thomas Yu
Verena Chung
Single Cell Signaling in Breast Cancer DREAM Consortium members
Bernd Bodenmiller
Julio Saez‐Rodriguez
author_sort Attila Gabor
collection DOAJ
description Abstract Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi‐signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time‐course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data.
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spelling doaj.art-bcd5b154a6e240949fe3c514a36f69b22024-03-02T22:00:33ZengSpringer NatureMolecular Systems Biology1744-42922021-10-011710n/an/a10.15252/msb.202110402Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowdAttila Gabor0Marco Tognetti1Alice Driessen2Jovan Tanevski3Baosen Guo4Wencai Cao5He Shen6Thomas Yu7Verena Chung8Single Cell Signaling in Breast Cancer DREAM Consortium membersBernd Bodenmiller9Julio Saez‐Rodriguez10Institute for Computational Biomedicine Heidelberg University and Heidelberg University Hospital Faculty of Medicine Bioquant Heidelberg GermanyDepartment of Quantitative Biomedicine & Institute of Molecular Life Sciences University of Zurich Zurich SwitzerlandInstitute for Computational Biomedicine Heidelberg University and Heidelberg University Hospital Faculty of Medicine Bioquant Heidelberg GermanyInstitute for Computational Biomedicine Heidelberg University and Heidelberg University Hospital Faculty of Medicine Bioquant Heidelberg GermanyDivision of AI & Bioinformatics Shenzhen Digital Life Institute Shenzhen ChinaDivision of AI & Bioinformatics Shenzhen Digital Life Institute Shenzhen ChinaDivision of AI & Bioinformatics Shenzhen Digital Life Institute Shenzhen ChinaSage Bionetworks Seattle WA USASage Bionetworks Seattle WA USADepartment of Quantitative Biomedicine & Institute of Molecular Life Sciences University of Zurich Zurich SwitzerlandInstitute for Computational Biomedicine Heidelberg University and Heidelberg University Hospital Faculty of Medicine Bioquant Heidelberg GermanyAbstract Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi‐signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time‐course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data.https://doi.org/10.15252/msb.202110402cell signalingcrowdsourcingmass cytometrypredictive modelingsingle cell
spellingShingle Attila Gabor
Marco Tognetti
Alice Driessen
Jovan Tanevski
Baosen Guo
Wencai Cao
He Shen
Thomas Yu
Verena Chung
Single Cell Signaling in Breast Cancer DREAM Consortium members
Bernd Bodenmiller
Julio Saez‐Rodriguez
Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
Molecular Systems Biology
cell signaling
crowdsourcing
mass cytometry
predictive modeling
single cell
title Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
title_full Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
title_fullStr Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
title_full_unstemmed Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
title_short Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
title_sort cell to cell and type to type heterogeneity of signaling networks insights from the crowd
topic cell signaling
crowdsourcing
mass cytometry
predictive modeling
single cell
url https://doi.org/10.15252/msb.202110402
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