METI: deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics

Jiahui Jiang, Yunhe Liu, Jiangjiang Qin, Jianfeng Chen, Jingjing Wu, Melissa P. Pizzi, Rossana Lazcano, Kohei Yamashita, Zhiyuan Xu, Guangsheng Pei, Kyung Serk Cho, Yanshuo Chu, Ansam Sinjab, Fuduan Peng, Xinmiao Yan, Guangchun Han, Ruiping Wang, Enyu Dai, Yibo Dai, Bogdan A. Czerniak, Andrew Futreal, Anirban Maitra, Alexander Lazar, Humam Kadara, Amir A. Jazaeri, Xiangdong Cheng, Jaffer Ajani, Jianjun Gao, Jian Hu () and Linghua Wang ()
Additional contact information
Jiahui Jiang: The University of Texas MD Anderson Cancer Center
Yunhe Liu: The University of Texas MD Anderson Cancer Center
Jiangjiang Qin: Zhejiang Cancer Hospital
Jianfeng Chen: The University of Texas MD Anderson Cancer Center
Jingjing Wu: The University of Texas MD Anderson Cancer Center
Melissa P. Pizzi: The University of Texas MD Anderson Cancer Center
Rossana Lazcano: The University of Texas MD Anderson Cancer Center
Kohei Yamashita: The University of Texas MD Anderson Cancer Center
Zhiyuan Xu: Zhejiang Cancer Hospital
Guangsheng Pei: The University of Texas MD Anderson Cancer Center
Kyung Serk Cho: The University of Texas MD Anderson Cancer Center
Yanshuo Chu: The University of Texas MD Anderson Cancer Center
Ansam Sinjab: The University of Texas MD Anderson Cancer Center
Fuduan Peng: The University of Texas MD Anderson Cancer Center
Xinmiao Yan: The University of Texas MD Anderson Cancer Center
Guangchun Han: The University of Texas MD Anderson Cancer Center
Ruiping Wang: The University of Texas MD Anderson Cancer Center
Enyu Dai: The University of Texas MD Anderson Cancer Center
Yibo Dai: The University of Texas MD Anderson Cancer Center
Bogdan A. Czerniak: The University of Texas MD Anderson Cancer Center
Andrew Futreal: The University of Texas MD Anderson Cancer Center
Anirban Maitra: The University of Texas MD Anderson Cancer Center
Alexander Lazar: The University of Texas MD Anderson Cancer Center
Humam Kadara: The University of Texas MD Anderson Cancer Center
Amir A. Jazaeri: The University of Texas MD Anderson Cancer Center
Xiangdong Cheng: Zhejiang Cancer Hospital
Jaffer Ajani: The University of Texas MD Anderson Cancer Center
Jianjun Gao: The University of Texas MD Anderson Cancer Center
Jian Hu: Emory School of Medicine
Linghua Wang: The University of Texas MD Anderson Cancer Center

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI’s robust and consistent performance.

Date: 2024
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DOI: 10.1038/s41467-024-51708-9

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