Histocat: analysis of cell phenotypes and interactions in multiplex image cytometry data

ABSTRACT Single-cell, spatially resolved omics analysis of tissues is poised to transform biomedical research and clinical practice. We have developed an open-source, computational histology

topography cytometry analysis toolbox (histoCAT) to enable interactive, quantitative, and comprehensive exploration of individual cell phenotypes, cell–cell interactions, microenvironments,

and morphological structures within intact tissues. We highlight the unique abilities of histoCAT through analysis of highly multiplexed mass cytometry images of human breast cancer

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VIEWED BY OTHERS THREE-DIMENSIONAL IMAGING MASS CYTOMETRY FOR HIGHLY MULTIPLEXED MOLECULAR AND CELLULAR MAPPING OF TISSUES AND THE TUMOR MICROENVIRONMENT Article Open access 24 December 2021

MCMICRO: A SCALABLE, MODULAR IMAGE-PROCESSING PIPELINE FOR MULTIPLEXED TISSUE IMAGING Article Open access 25 November 2021 SEMI-AUTOMATED APPROACHES FOR INTERROGATING SPATIAL HETEROGENEITY

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1084–1096 (2016). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We would like to thank the Bodenmiller lab for support and fruitful discussions. Thank you to open-source

softwares like “cyt”, “CellProfiler,” and many others. This work was supported by the Swiss National Science Foundation (SNSF) R'Equip grant 316030-139220, an SNSF Assistant

Professorship grant PP00P3-144874, a Swiss Cancer League grant, the PhosphonetPPM and MetastasiX SystemsX grants, and funding from the European Research Council (ERC) under the European

Union′s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336921. D. Schapiro was supported by the Forschungskredit of the University of Zurich, grant FK-74419-01-01, and

the BioEntrepreneur-Fellowship of the University of Zurich, reference no. BIOEF-17-001. H.W.J. and D. Schulz are supported by European Molecular Biology Organization (EMBO) Long Term

Fellowships cofunded by the European Commission (LTFCOFUND2013 and 2014), grants ALTF-711 2015 and ALTF-970 2014, respectively. H.W.J. was also supported by a Transition Postdoc Fellowship

from the Swiss SystemsX.ch initiative ref. 2015/344, evaluated by the Swiss National Science Foundation. AUTHOR INFORMATION Author notes * Swetha Raghuraman Present address: Institute of

Cell Biology, ZMBE, University of Münster, Münster, Germany * Charlotte Giesen Present address: F. Hoffmann-La Roche Ltd, Kaiseraugst, Switzerland * Denis Schapiro and Hartland W Jackson:

These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland Denis Schapiro, Hartland W Jackson,

 Swetha Raghuraman, Jana R Fischer, Vito R T Zanotelli, Daniel Schulz, Charlotte Giesen, Raúl Catena & Bernd Bodenmiller * Life Science Zurich Graduate School, ETH Zurich and University

of Zurich, Zurich, Switzerland Denis Schapiro & Vito R T Zanotelli * Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland Zsuzsanna Varga Authors * Denis

Schapiro View author publications You can also search for this author inPubMed Google Scholar * Hartland W Jackson View author publications You can also search for this author inPubMed 

Google Scholar * Swetha Raghuraman View author publications You can also search for this author inPubMed Google Scholar * Jana R Fischer View author publications You can also search for this

author inPubMed Google Scholar * Vito R T Zanotelli View author publications You can also search for this author inPubMed Google Scholar * Daniel Schulz View author publications You can

also search for this author inPubMed Google Scholar * Charlotte Giesen View author publications You can also search for this author inPubMed Google Scholar * Raúl Catena View author

publications You can also search for this author inPubMed Google Scholar * Zsuzsanna Varga View author publications You can also search for this author inPubMed Google Scholar * Bernd

Bodenmiller View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS D. Schapiro, H.W.J., and B.B. conceived of the project and software. H.W.J.,

C.G., and R.C. collected samples and validated antibodies. Z.V. assembled, classified, and provided tumor samples. H.W.J. completed the staining and image acquisition. D. Schapiro, S.R., and

J.R.F. wrote the code. D. Schapiro, H.W.J., and D. Schulz tested software on multiple data sources. D. Schapiro, H.W.J., and V.R.T.Z. analyzed the images and single-cell data. D. Schapiro,

H.W.J., and B.B. prepared the figures and wrote the manuscript. B.B. directed the project. CORRESPONDING AUTHOR Correspondence to Bernd Bodenmiller. ETHICS DECLARATIONS COMPETING INTERESTS

The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–9, Supplementary Table 1 and Supplementary Notes 1–4.

(PDF 69995 kb) LIFE SCIENCES REPORTING SUMMARY Life Sciences Reporting Summary (PDF 129 kb) SUPPLEMENTARY TABLE 2 Patient Metadata (XLSX 47 kb) SUPPLEMENTARY DATASET 1 Source Data for Figure

2 (TXT 12656 kb) SUPPLEMENTARY DATASET 2 Source Data for Supplementary Figure 3 (XLS 80 kb) SUPPLEMENTARY SOFTWARE 1 histoCAT_MacOS12 (ZIP 17932 kb) SUPPLEMENTARY SOFTWARE 2

histoCAT_Windows7 (EXE 20372 kb) SUPPLEMENTARY SOFTWARE 3 histoCAT_Windows10 (EXE 19986 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Schapiro, D.,

Jackson, H., Raghuraman, S. _et al._ histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data. _Nat Methods_ 14, 873–876 (2017).

https://doi.org/10.1038/nmeth.4391 Download citation * Received: 07 February 2017 * Accepted: 07 July 2017 * Published: 07 August 2017 * Issue Date: 01 September 2017 * DOI:

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