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A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes

View ORCID ProfileAndrea J. Radtke, View ORCID ProfileEkaterina Postovalova, View ORCID ProfileArina Varlamova, View ORCID ProfileAlexander Bagaev, View ORCID ProfileMaria Sorokina, View ORCID ProfileOlga Kudryashova, View ORCID ProfileMark Meerson, View ORCID ProfileMargarita Polyakova, View ORCID ProfileIlia Galkin, View ORCID ProfileViktor Svekolkin, View ORCID ProfileSergey Isaev, Grigory Perelman, View ORCID ProfileYaroslav Lozinsky, View ORCID ProfileZiv Yaniv, View ORCID ProfileBradley C. Lowekamp, View ORCID ProfileEmily Speranza, View ORCID ProfileLi Yao, View ORCID ProfileStefania Pittaluga, Arthur L. Shaffer III, View ORCID ProfileDanny Jonigk, View ORCID ProfileJames D. Phelan, Theresa Davies-Hill, Da Wei Huang, View ORCID ProfilePavel Ovcharov, Krystle Nomie, View ORCID ProfileEkaterina Nuzhdina, View ORCID ProfileNikita Kotlov, View ORCID ProfileRavshan Ataullakhanov, View ORCID ProfileNathan Fowler, View ORCID ProfileMichael Kelly, View ORCID ProfileJagan Muppidi, View ORCID ProfileJeremy Davis, Jonathan M. Hernandez, Wyndham H. Wilson, View ORCID ProfileElaine S. Jaffe, View ORCID ProfileLouis M. Staudt, View ORCID ProfileMark Roschewski, View ORCID ProfileRonald N. Germain
doi: https://doi.org/10.1101/2022.06.03.494716
Andrea J. Radtke
1Lymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA
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  • ORCID record for Andrea J. Radtke
  • For correspondence: andrea.radtke@nih.gov
Ekaterina Postovalova
2BostonGene, Waltham, MA, 02453, USA
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  • ORCID record for Ekaterina Postovalova
Arina Varlamova
2BostonGene, Waltham, MA, 02453, USA
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Alexander Bagaev
2BostonGene, Waltham, MA, 02453, USA
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Maria Sorokina
2BostonGene, Waltham, MA, 02453, USA
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Olga Kudryashova
2BostonGene, Waltham, MA, 02453, USA
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  • ORCID record for Olga Kudryashova
Mark Meerson
2BostonGene, Waltham, MA, 02453, USA
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Margarita Polyakova
2BostonGene, Waltham, MA, 02453, USA
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Ilia Galkin
2BostonGene, Waltham, MA, 02453, USA
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Viktor Svekolkin
2BostonGene, Waltham, MA, 02453, USA
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Sergey Isaev
2BostonGene, Waltham, MA, 02453, USA
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Grigory Perelman
2BostonGene, Waltham, MA, 02453, USA
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Yaroslav Lozinsky
2BostonGene, Waltham, MA, 02453, USA
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Ziv Yaniv
3Bioinformatics and Computational Bioscience Branch, NIAID, NIH, Bethesda, MD, USA
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Bradley C. Lowekamp
3Bioinformatics and Computational Bioscience Branch, NIAID, NIH, Bethesda, MD, USA
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  • ORCID record for Bradley C. Lowekamp
Emily Speranza
1Lymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA
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Li Yao
4Howard Hughes Medical Institute, Chevy Chase, MD, USA
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Stefania Pittaluga
5Laboratory of Pathology, NCI, NIH, Bethesda, MD, USA
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  • ORCID record for Stefania Pittaluga
Arthur L. Shaffer III
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
7Tumor Targeted Delivery, Heme Malignancy Target Discovery Group, AstraZeneca, Gaithersburg, MD, USA
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Danny Jonigk
8Institute of Pathology, Hannover Medical School, Hannover, Germany, Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH)
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James D. Phelan
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
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Theresa Davies-Hill
5Laboratory of Pathology, NCI, NIH, Bethesda, MD, USA
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Da Wei Huang
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
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Pavel Ovcharov
2BostonGene, Waltham, MA, 02453, USA
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Krystle Nomie
2BostonGene, Waltham, MA, 02453, USA
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Ekaterina Nuzhdina
2BostonGene, Waltham, MA, 02453, USA
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Nikita Kotlov
2BostonGene, Waltham, MA, 02453, USA
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Ravshan Ataullakhanov
2BostonGene, Waltham, MA, 02453, USA
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Nathan Fowler
2BostonGene, Waltham, MA, 02453, USA
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Michael Kelly
9CCR Single Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Bethesda, MD, USA
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  • ORCID record for Michael Kelly
Jagan Muppidi
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
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Jeremy Davis
10Surgical Oncology Program, Metastasis Biology Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
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Jonathan M. Hernandez
10Surgical Oncology Program, Metastasis Biology Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
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Wyndham H. Wilson
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
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Elaine S. Jaffe
5Laboratory of Pathology, NCI, NIH, Bethesda, MD, USA
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Louis M. Staudt
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
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Mark Roschewski
6Lymphoid Malignancies Branch, NCI, NIH, Bethesda, MD, USA
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Ronald N. Germain
1Lymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA
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SUMMARY

Reference atlases, molecular and spatial maps of mammalian tissues, are critical resources for discovery efforts and translational research. Their utility is dependent on operationalizing the resulting data by identifying cell types, histological patterns, and predictive biomarkers underlying health and disease. The human lymph node (LN) offers a compelling use case because of its importance in immunity, structural and cellular diversity, and neoplastic involvement. One hematological malignancy, follicular lymphoma (FL), evolves from developmentally blocked germinal center B cells residing in and trafficking through these tissues. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Here, we present an integrated portrait of healthy and FL LNs using multiple genomic and advanced imaging technologies. By leveraging the strengths of each platform, we identified several tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk of FL patients.

Competing Interest Statement

Nathan Fowler is the Chief Medical Officer of BostonGene, Corp and a Professor at the University of Texas MD Anderson Cancer Center. Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Maria Sorokina, Olga Kudryashova, Alexander Bagaev, Mark Meerson, Margarita Polyakova, Ilia Galkin, Viktor Svekolkin, Sergei Isaev, Grigory Perelman, Yaroslav Lozinsky, Pavel Ovcharov, Krystle Nomie, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Attaulakhanov were employees at BostonGene at the time the study was performed. Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Olga Kudryashova, Mark Meerson, Ilia Galkin, Viktor Svekolkin, Pavel Ovcharov, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Attaulakhanov are inventors on patent applications related to MxIF pipelines and proprietary BostonGene software. All other authors declare no other competing financial interests.

Footnotes

  • https://doi.org/10.5281/zenodo.6536724

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes
Andrea J. Radtke, Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Maria Sorokina, Olga Kudryashova, Mark Meerson, Margarita Polyakova, Ilia Galkin, Viktor Svekolkin, Sergey Isaev, Grigory Perelman, Yaroslav Lozinsky, Ziv Yaniv, Bradley C. Lowekamp, Emily Speranza, Li Yao, Stefania Pittaluga, Arthur L. Shaffer III, Danny Jonigk, James D. Phelan, Theresa Davies-Hill, Da Wei Huang, Pavel Ovcharov, Krystle Nomie, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Ataullakhanov, Nathan Fowler, Michael Kelly, Jagan Muppidi, Jeremy Davis, Jonathan M. Hernandez, Wyndham H. Wilson, Elaine S. Jaffe, Louis M. Staudt, Mark Roschewski, Ronald N. Germain
bioRxiv 2022.06.03.494716; doi: https://doi.org/10.1101/2022.06.03.494716
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A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes
Andrea J. Radtke, Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Maria Sorokina, Olga Kudryashova, Mark Meerson, Margarita Polyakova, Ilia Galkin, Viktor Svekolkin, Sergey Isaev, Grigory Perelman, Yaroslav Lozinsky, Ziv Yaniv, Bradley C. Lowekamp, Emily Speranza, Li Yao, Stefania Pittaluga, Arthur L. Shaffer III, Danny Jonigk, James D. Phelan, Theresa Davies-Hill, Da Wei Huang, Pavel Ovcharov, Krystle Nomie, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Ataullakhanov, Nathan Fowler, Michael Kelly, Jagan Muppidi, Jeremy Davis, Jonathan M. Hernandez, Wyndham H. Wilson, Elaine S. Jaffe, Louis M. Staudt, Mark Roschewski, Ronald N. Germain
bioRxiv 2022.06.03.494716; doi: https://doi.org/10.1101/2022.06.03.494716

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