CytofIn enables integrated analysis of public mass cytometry datasets using generalized anchors

• Published in: Nature communications Vol. 13; no. 1; pp. 934 - 15
• Main Authors: Lo, Yu-Chen, Keyes, Timothy J., Jager, Astraea, Sarno, Jolanda, Domizi, Pablo, Majeti, Ravindra, Sakamoto, Kathleen M., Lacayo, Norman, Mullighan, Charles G., Waters, Jeffrey, Sahaf, Bita, Bendall, Sean C., Davis, Kara L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 631/114/2401; 631/1647/794; 692/699/67/1990/283/2125; 82/1; 82/58; 82/80; Algorithms; Cancer; Comparative analysis; Computational Biology - methods; Cytometry; Data integration; Datasets; Datasets as Topic; Flow Cytometry - methods; Humanities and Social Sciences; Humans; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Integration; Leukemia; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Melanoma - drug therapy; Melanoma - immunology; Melanoma - pathology; multidisciplinary; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Public domain; Robustness; Science; Science (multidisciplinary); Single-Cell Analysis; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Stable channels
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28484-5

The increasing use of mass cytometry for analyzing clinical samples offers the possibility to perform comparative analyses across public datasets. However, challenges in batch normalization and data integration limit the comparison of datasets not intended to be analyzed together. Here, we present a data integration strategy, CytofIn, using generalized anchors to integrate mass cytometry datasets from the public domain. We show that low-variance controls, such as healthy samples and stable channels, are inherently homogeneous, robust against stimulation, and can serve as generalized anchors for batch correction. Single-cell quantification comparing mass cytometry data from 989 leukemia files pre- and post normalization with CytofIn demonstrates effective batch correction while recapitulating the gold-standard bead normalization. CytofIn integration of public cancer datasets enabled the comparison of immune features across histologies and treatments. We demonstrate the ability to integrate public datasets without necessitating identical control samples or bead standards for fast and robust analysis using CytofIn. Challenges in batch normalization and data integration limit the comparison of existing mass cytometry datasets. Here, the authors report CytofIn that can integrate mass cytometry datasets from the public domain and reveal cellular features associated with immune oncology by analyzing five public cancer datasets.