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MetaTiME: Meta-components of the Tumor Immune Microenvironment

View ORCID ProfileYi Zhang, Guanjue Xiang, Alva Yijia Jiang, Allen Lynch, Zexian Zeng, View ORCID ProfileChenfei Wang, Wubing Zhang, Jingyu Fan, Jiajinlong Kang, Shengqing Stan Gu, Changxin Wan, Boning Zhang, X. Shirley Liu, Myles Brown, Clifford A Meyer
doi: https://doi.org/10.1101/2022.08.05.502989
Yi Zhang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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  • ORCID record for Yi Zhang
Guanjue Xiang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Alva Yijia Jiang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
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Allen Lynch
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Zexian Zeng
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Chenfei Wang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Wubing Zhang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Jingyu Fan
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Jiajinlong Kang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
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Shengqing Stan Gu
4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
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Changxin Wan
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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Boning Zhang
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
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X. Shirley Liu
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
3Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
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  • For correspondence: cliff_meyer@ds.dfci.harvard.edu myles_brown@dfci.harvard.edu xsliu.res@gmail.com
Myles Brown
3Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
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  • For correspondence: cliff_meyer@ds.dfci.harvard.edu myles_brown@dfci.harvard.edu xsliu.res@gmail.com
Clifford A Meyer
1Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02215 USA
3Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA
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  • For correspondence: cliff_meyer@ds.dfci.harvard.edu myles_brown@dfci.harvard.edu xsliu.res@gmail.com
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Abstract

Recent advances in single-cell RNA sequencing have revealed heterogeneous cell types and gene expression states in the non-cancerous cells in tumors. The integration of multiple scRNA-seq datasets across tumors can reveal common cell types and states in the tumor microenvironment (TME). We developed a data driven framework, MetaTiME, to overcome the limitations in resolution and consistency that result from manual labelling using known gene markers. Using millions of TME single cells, MetaTiME learns meta-components that encode independent components of gene expression observed across cancer types. The meta-components are biologically interpretable as cell types, cell states, and signaling activities. By projecting onto the MetaTiME space, we provide a tool to annotate cell states and signature continuums for TME scRNA-seq data. Leveraging epigenetics data, MetaTiME reveals critical transcriptional regulators for the cell states. Overall, MetaTiME learns data-driven meta-components that depict cellular states and gene regulators for tumor immunity and cancer immunotherapy.

Competing Interest Statement

MB is a consultant to and receives sponsored research support from Novartis. MB serves on the SAB of H3 Biomedicine, Kronos Bio, and GV20 Oncotherapy. X.S.L conducted the work while being on the faculty at DFCI, and is currently a board member and CEO of GV20 Therapeutics. The remaining authors declare no competing interests.

Footnotes

  • Meta-component annotation is updated; Main text and Figures revised; Supplemental files revised.

  • https://github.com/yi-zhang/MetaTiME

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 12, 2023.
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MetaTiME: Meta-components of the Tumor Immune Microenvironment
Yi Zhang, Guanjue Xiang, Alva Yijia Jiang, Allen Lynch, Zexian Zeng, Chenfei Wang, Wubing Zhang, Jingyu Fan, Jiajinlong Kang, Shengqing Stan Gu, Changxin Wan, Boning Zhang, X. Shirley Liu, Myles Brown, Clifford A Meyer
bioRxiv 2022.08.05.502989; doi: https://doi.org/10.1101/2022.08.05.502989
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MetaTiME: Meta-components of the Tumor Immune Microenvironment
Yi Zhang, Guanjue Xiang, Alva Yijia Jiang, Allen Lynch, Zexian Zeng, Chenfei Wang, Wubing Zhang, Jingyu Fan, Jiajinlong Kang, Shengqing Stan Gu, Changxin Wan, Boning Zhang, X. Shirley Liu, Myles Brown, Clifford A Meyer
bioRxiv 2022.08.05.502989; doi: https://doi.org/10.1101/2022.08.05.502989

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