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UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues

View ORCID ProfileClarence Yapp, View ORCID ProfileEdward Novikov, View ORCID ProfileWon-Dong Jang, View ORCID ProfileTuulia Vallius, View ORCID ProfileYu-An Chen, Marcelo Cicconet, View ORCID ProfileZoltan Maliga, View ORCID ProfileConnor A. Jacobson, View ORCID ProfileDonglai Wei, View ORCID ProfileSandro Santagata, Hanspeter Pfister, View ORCID ProfilePeter K. Sorger
doi: https://doi.org/10.1101/2021.04.02.438285
Clarence Yapp
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
2Image and Data Analysis Core, Harvard Medical School, Boston, MA 02115 Human Tumor Atlas Network
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  • For correspondence: clarence@hms.harvard.edu
Edward Novikov
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
3School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138
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Won-Dong Jang
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
3School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138
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Tuulia Vallius
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
4Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA, 02115
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Yu-An Chen
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
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Marcelo Cicconet
2Image and Data Analysis Core, Harvard Medical School, Boston, MA 02115 Human Tumor Atlas Network
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Zoltan Maliga
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
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Connor A. Jacobson
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
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Donglai Wei
3School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138
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Sandro Santagata
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
4Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA, 02115
5Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115
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Hanspeter Pfister
3School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138
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Peter K. Sorger
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115
4Ludwig Center for Cancer Research at Harvard, Harvard Medical School, Boston, MA, 02115
6Department of Systems Biology, Harvard Medical School, Boston, MA, 02115
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ABSTRACT

Newly developed technologies have made it feasible to routinely collect highly multiplexed (20-60 channel) images at subcellular resolution from human tissues for research and diagnostic purposes. Extracting single cell data from such images requires efficient and accurate image segmentation, a challenging problem that has recently benefited from the use of deep learning. In this paper, we demonstrate two approaches to improving tissue segmentation that are applicable to multiple deep learning frameworks. The first uses “real augmentations” that comprise defocused and saturated image data collected on the same instruments as the actual data; using real augmentation improves model accuracy to a significantly greater degree than computational augmentation (Gaussian blurring). The second involves imaging the nuclear envelope to better identify nuclear outlines. The two approaches cumulatively and substantially improve segmentation on a wide range of tissue types and provide a set of improved segmentation models. We speculate that the use of real augmentations may have applications in image processing outside of microscopy.

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. The other authors declare no outside interests.

Footnotes

  • Clarence Yapp clarence{at}hms.harvard.edu, Edward Novikov edward_novikov{at}seas.harvard.edu, Won-Dong Jang wdjang{at}seas.harvard.edu, Tuulia Vallius tuulia_vallius{at}hms.harvard.edu, Yu-An Chen yu-an_chen{at}hms.harvard.edu, Marcelo Cicconet marcelo_cicconet{at}hms.harvard.edu, Zoltan Maliga zoltan_maliga{at}hms.harvard.edu, Connor A. Jacobson connor_jacobson{at}hms.harvard.edu, Donglai Wei donglai{at}seas.harvard.edu, Sandro Santagata ssantagata{at}bics.bwh.harvard.edu, Hanspeter Pfister pfister{at}seas.harvard.edu, Peter K. Sorger peter_sorger{at}hms.harvard.edu

  • -Additional segmentation metrics added -Additional author added -Interobserver agreement metric added -Supplementary file updated

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 4.0 International license.
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Posted February 25, 2022.
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UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues
Clarence Yapp, Edward Novikov, Won-Dong Jang, Tuulia Vallius, Yu-An Chen, Marcelo Cicconet, Zoltan Maliga, Connor A. Jacobson, Donglai Wei, Sandro Santagata, Hanspeter Pfister, Peter K. Sorger
bioRxiv 2021.04.02.438285; doi: https://doi.org/10.1101/2021.04.02.438285
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UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues
Clarence Yapp, Edward Novikov, Won-Dong Jang, Tuulia Vallius, Yu-An Chen, Marcelo Cicconet, Zoltan Maliga, Connor A. Jacobson, Donglai Wei, Sandro Santagata, Hanspeter Pfister, Peter K. Sorger
bioRxiv 2021.04.02.438285; doi: https://doi.org/10.1101/2021.04.02.438285

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