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bioRxiv · 10.1101/2022.08.05.502989

MetaTiME: Meta-components of the Tumor Immune Microenvironment

Zhang, Y.·Xiang, G.·Jiang, A. Y.·Lynch, A.·Zeng, Z.·Wang, C.·Zhang, W.·Fan, J.·Kang, J.·Gu, S.·Wan, C.·Zhang, B.·Liu, X. S.·Brown, M.·Meyer, C. A.
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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.

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Zhang, Y., Xiang, G., Jiang, A. Y., Lynch, A., Zeng, Z., Wang, C., Zhang, W., Fan, J., Kang, J., Gu, S., Wan, C., Zhang, B., Liu, X. S., Brown, M., Meyer, C. A.. 2022-08-06. MetaTiME: Meta-components of the Tumor Immune Microenvironment. https://doi.org/10.1101/2022.08.05.502989

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