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

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....

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Main Authors: Gabor, Attila (Author) , Tognetti, Marco (Author) , Driessen, Alice (Author) , Tanevski, Jovan (Author) , Guo, Baosen (Author) , Cao, Wencai (Author) , Shen, He (Author) , Yu, Thomas (Author) , Chung, Verena (Author) , Bodenmiller, Bernd (Author) , Sáez Rodríguez, Julio (Author)
Format: Article (Journal)
Language:English
Published: 28 September 2021
In: Molecular systems biology
Year: 2021, Volume: 17, Issue: 10, Pages: 1-16
ISSN:1744-4292
DOI:10.15252/msb.202110402
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/msb.202110402
Verlag, lizenzpflichtig, Volltext: https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=DOISource&SrcApp=WOS&KeyAID=10.15252%2Fmsb.202110402&DestApp=DOI&SrcAppSID=E6GODfOazgZGetsaLqg&SrcJTitle=MOLECULAR+SYSTEMS+BIOLOGY&DestDOIRegistrantName=EMBO
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Author Notes: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 and Julio Saez-Rodriguez
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Summary: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.
Item Description:Gesehen am 26.01.2022
Physical Description:Online Resource
ISSN:1744-4292
DOI:10.15252/msb.202110402