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MCMICRO: A scalable, modular image-processing pipeline for multiplexed tissue imaging

View ORCID ProfileDenis Schapiro, View ORCID ProfileArtem Sokolov, View ORCID ProfileClarence Yapp, View ORCID ProfileJeremy L. Muhlich, View ORCID ProfileJoshua Hess, View ORCID ProfileJia-Ren Lin, View ORCID ProfileYu-An Chen, View ORCID ProfileMaulik K. Nariya, View ORCID ProfileGregory J. Baker, Juha Ruokonen, View ORCID ProfileZoltan Maliga, View ORCID ProfileConnor A. Jacobson, View ORCID ProfileSamouil L. Farhi, View ORCID ProfileDomenic Abbondanza, View ORCID ProfileEliot T. McKinley, View ORCID ProfileCourtney Betts, View ORCID ProfileAviv Regev, View ORCID ProfileRobert J. Coffey, View ORCID ProfileLisa M. Coussens, View ORCID ProfileSandro Santagata, View ORCID ProfilePeter K. Sorger
doi: https://doi.org/10.1101/2021.03.15.435473
Denis Schapiro
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
3Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA
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Artem Sokolov
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Clarence Yapp
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
4Image and Data Analysis Core, Harvard Medical School, Boston, MA
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Jeremy L. Muhlich
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Joshua Hess
5Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Jia-Ren Lin
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Yu-An Chen
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Maulik K. Nariya
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Gregory J. Baker
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Juha Ruokonen
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Zoltan Maliga
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Connor A. Jacobson
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
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Samouil L. Farhi
3Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA
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Domenic Abbondanza
3Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA
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Eliot T. McKinley
6Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN
7Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN
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Courtney Betts
8Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR
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Aviv Regev
3Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA
9Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
10Genentech, South San Francisco, CA, USA
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Robert J. Coffey
11Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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Lisa M. Coussens
8Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR
12Knight Cancer Institute, Oregon Health & Science University, Portland, OR
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Sandro Santagata
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
13Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
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Peter K. Sorger
1Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA
2Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA
14Department of Systems Biology, Harvard Medical School, Boston, MA
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  • For correspondence: peter_sorger@hms.harvard.edu sorger_admin@hms.harvard.edu
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ABSTRACT

Highly multiplexed tissue imaging makes molecular analysis of single cells possible in a preserved spatial context. However, reproducible analysis of the underlying data poses a substantial computational challenge. Here we describe a modular and open-source computational pipeline (MCMICRO) for performing the sequential steps needed to transform large, multi-channel whole slide images into single-cell data. We demonstrate use of MCMICRO on images of different tissues and tumors acquired using multiple imaging platforms, thereby providing a solid foundation for the continued development of tissue imaging software.

Competing Interest Statement

PKS is a member of the SAB or BOD member of Applied Biomath, RareCyte Inc., and Glencoe Software, which distributes a commercial version of the OMERO database; PKS is also a member of the NanoString SAB. In the last five years the Sorger lab has received research funding from Novartis and Merck. Sorger declares that none of these relationships have influenced the content of this manuscript. SS is a consultant for RareCyte Inc. A. R. is a cofounder and equity holder of Celsius Therapeutics, an equity holder in Immunitas and, until 31 July 2020, was an SAB member of Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov. Since August 1, 2020, A. R. has been an employee of Genentech. The other authors declare no outside interests.

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 March 16, 2021.
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MCMICRO: A scalable, modular image-processing pipeline for multiplexed tissue imaging
Denis Schapiro, Artem Sokolov, Clarence Yapp, Jeremy L. Muhlich, Joshua Hess, Jia-Ren Lin, Yu-An Chen, Maulik K. Nariya, Gregory J. Baker, Juha Ruokonen, Zoltan Maliga, Connor A. Jacobson, Samouil L. Farhi, Domenic Abbondanza, Eliot T. McKinley, Courtney Betts, Aviv Regev, Robert J. Coffey, Lisa M. Coussens, Sandro Santagata, Peter K. Sorger
bioRxiv 2021.03.15.435473; doi: https://doi.org/10.1101/2021.03.15.435473
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MCMICRO: A scalable, modular image-processing pipeline for multiplexed tissue imaging
Denis Schapiro, Artem Sokolov, Clarence Yapp, Jeremy L. Muhlich, Joshua Hess, Jia-Ren Lin, Yu-An Chen, Maulik K. Nariya, Gregory J. Baker, Juha Ruokonen, Zoltan Maliga, Connor A. Jacobson, Samouil L. Farhi, Domenic Abbondanza, Eliot T. McKinley, Courtney Betts, Aviv Regev, Robert J. Coffey, Lisa M. Coussens, Sandro Santagata, Peter K. Sorger
bioRxiv 2021.03.15.435473; doi: https://doi.org/10.1101/2021.03.15.435473

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