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Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section

View ORCID ProfileJia-Ren Lin, View ORCID ProfileYu-An Chen, View ORCID ProfileDaniel Campton, View ORCID ProfileJeremy Cooper, View ORCID ProfileShannon Coy, View ORCID ProfileClarence Yapp, View ORCID ProfileJuliann B. Tefft, View ORCID ProfileErin McCarty, View ORCID ProfileKeith L. Ligon, View ORCID ProfileScott J. Rodig, View ORCID ProfileSteven Reese, View ORCID ProfileTad George, View ORCID ProfileSandro Santagata, View ORCID ProfilePeter K. Sorger
doi: https://doi.org/10.1101/2022.09.28.509927
Jia-Ren Lin
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
2Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
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  • ORCID record for Jia-Ren Lin
Yu-An Chen
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
2Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
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Daniel Campton
3RareCyte, Inc., 2601 Fourth Ave., Seattle, WA, 98121, USA.
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Jeremy Cooper
3RareCyte, Inc., 2601 Fourth Ave., Seattle, WA, 98121, USA.
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Shannon Coy
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
4Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
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Clarence Yapp
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
2Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
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Juliann B. Tefft
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
2Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
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Erin McCarty
3RareCyte, Inc., 2601 Fourth Ave., Seattle, WA, 98121, USA.
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Keith L. Ligon
4Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
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Scott J. Rodig
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Steven Reese
3RareCyte, Inc., 2601 Fourth Ave., Seattle, WA, 98121, USA.
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Tad George
3RareCyte, Inc., 2601 Fourth Ave., Seattle, WA, 98121, USA.
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Sandro Santagata
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
2Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
4Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
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Peter K. Sorger
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
2Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
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  • For correspondence: peter_sorger@hms.harvard.edu lsp-papers@hms.harvard.edu
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ABSTRACT

Precision medicine is critically dependent on better methods for diagnosing and staging disease and predicting drug response. Histopathology using Hematoxylin and Eosin (H&E) stained tissue - not genomics – remains the primary diagnostic modality in cancer. Moreover, recently developed, highly multiplexed tissue imaging represents a means of enhancing histology workflows with single cell mechanisms. Here we describe an approach for collecting and analyzing H&E and high-plex immunofluorescence (IF) images from the same cells in a whole-slide format suitable for translational and clinical research and eventual deployment in diagnosis. Using data from 40 human colorectal cancer resections (60 million cells) we show that IF and H&E images provide human experts and machine learning algorithms with complementary information. We demonstrate the automated generation and ranking of computational models, based either on immune infiltration or tumor-intrinsic features, that are highly predictive of progression-free survival. When these models are combined, a hazard ratio of ∼0.045 is achieved, demonstrating the ability of multi-modal digital pathology to generate high-performance and interpretable biomarkers.

Competing Interest Statement

PKS is a co-founder and member of the BOD of Glencoe Software, a member of the BOD for Applied Biomath, and a member of the SAB for RareCyte, NanoString, and Montai Health; he holds equity in Glencoe, Applied Biomath, and RareCyte. PKS is a consultant for Merck and the Sorger lab has received research funding from Novartis and Merck in the past five years. YC is a consultant for RareCyte. DC, JC, EM, SR, and TG are employees of RareCyte. The DFCI receives funding for KLL research from the following entities: Amgen, Travera, and X4. DFCI and KLL have patents related to molecular diagnostics of cancer. SJR receives research support from Bristol-Myers-Squibb and KITE/Gilead. SJR is on the Scientific Advisory Board for Immunitas Therapeutics. The other authors declare no outside interests.

Footnotes

  • Human Tissue Atlas Center

  • https://labsyspharm.github.io/orion-crc/

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 September 30, 2022.
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Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section
Jia-Ren Lin, Yu-An Chen, Daniel Campton, Jeremy Cooper, Shannon Coy, Clarence Yapp, Juliann B. Tefft, Erin McCarty, Keith L. Ligon, Scott J. Rodig, Steven Reese, Tad George, Sandro Santagata, Peter K. Sorger
bioRxiv 2022.09.28.509927; doi: https://doi.org/10.1101/2022.09.28.509927
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Multi-modal digital pathology for colorectal cancer diagnosis by high-plex immunofluorescence imaging and traditional histology of the same tissue section
Jia-Ren Lin, Yu-An Chen, Daniel Campton, Jeremy Cooper, Shannon Coy, Clarence Yapp, Juliann B. Tefft, Erin McCarty, Keith L. Ligon, Scott J. Rodig, Steven Reese, Tad George, Sandro Santagata, Peter K. Sorger
bioRxiv 2022.09.28.509927; doi: https://doi.org/10.1101/2022.09.28.509927

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