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Title: National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions

Abstract

A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts’ opinion on the development and application of multi-omic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular and functional aberrations within the lesion and within individual cells. Additionally, single-cell proteomic data will be essential for the establishment of new tools that with searchable and scalable features that include spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included: • The best way/s to analyze single-cells from fresh and preserved tissue • Detection and analysis of secreted molecules and from single cells, especially from a tissue slice • Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment • Multi-omic integration of data to support and inform proteomic measurements • Subcellular organelles – identifying abnormal structure, function, distribution and location within individual premalignant and malignant cells • How to improve themore » dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post translational modifications (PTM) • The depth of coverage measured concurrently using single-cell techniques • Quantitation - absolute or semiquantitative? • Single methodology or multiplexed combinations? • Application of analytical methods for identification of biologically significant subsets • Data visualization of N-dimensional datasets • How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME) • Associations between intrinsic cellular processes and extrinsic stimuli • How to predict cellular responses to stress inducing stimuli • Identification of new markers for prediction of progression from precursor, benign and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells • Identification of new targets for immunoprevention or immunotherapy – identification of neoantigens and surfactome of individual cells within a lesion« less

Authors:
ORCiD logo [1];  [2];  [1];  [3];  [4];  [5];  [6]; ORCiD logo [7];  [8];  [9]; ORCiD logo [10];  [11];  [12];  [13]; ORCiD logo [14];  [15];  [16]; ORCiD logo [17];  [18];  [19] more »; ORCiD logo [14];  [1] « less
+ Show Author Affiliations
  1. National Cancer Institute, Bethesda, MD (United States). Cancer Biomarkers Research Group
  2. Inst. for Systems Biology, Seattle, WA (United States)
  3. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States)
  4. Harvard Medical School, Boston, MA (United States). Blavatnik Inst. for Biomedical Information
  5. Klarman Cell Observatory, Broad Inst., Boston, MA (United States)
  6. National Cancer Inst., Bethesda, MD (United States). Cancer Data Science Lab., Center for Cancer Research,
  7. KTH Royal Inst. of Technology, Stockholm (Sweden). Science for Life Lab.
  8. GE Global Research, Niskayuna, New York (United States). Life Sciences and Molecular Diagnostics Lab.
  9. Stanford Univ., CA (United States). School of Medicine, Baxter Lab. in Stem Cell Biology
  10. Univ. of California, San Francisco, CA (United States)
  11. Rockefeller Univ., New York, NY (United States). Lab. of Cellular and Structural Biology
  12. Oregon Health and Science Univ., Portland, OR (United States). Center for Spatial Systems Biomedicine
  13. National Inst. of Health (NIH), Bethesda, MD (United States). Lab. of Immune System Biology, National Inst. of Allergy and Infectious Diseases
  14. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  15. Encodia, Inc., San Diego, CA (United States)
  16. Harvard Univ., Boston, MA (United States)
  17. The Scripps Research Inst., La Jolla, CA (United States)
  18. Rockefeller Univ., New York, NY (United States). Lab. of Mass Spectrometry and Gaseous Ion Chemistry
  19. Boston Children’s Hospital and Harvard Univ. Medical School, Boston, MA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1639039
Report Number(s):
PNNL-SA-152101
Journal ID: ISSN 1535-3893
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Proteome Research
Additional Journal Information:
Journal Volume: 19; Journal Issue: 5; Journal ID: ISSN 1535-3893
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; single-cell proteomics; single-cell mass spectrometry; targeted proteomics; precursor lesion; precancer; tumorigenic lesion; lesion’s heterogeneity; clonal evolution; spatial and temporal cartography; biomarkers; early detection targets for prevention and therapy

Citation Formats

Kagan, Jacob, Moritz, Robert L., Mazurchuk, Richard, Lee, Je Hyuk, Kharchenko, Peter Vasili, Rozenblatt-Rosen, Orit, Ruppin, Eytan, Edfors, Fredrik, Ginty, Fiona, Goltsev, Yury, Wells, James A., LaCava, John, Riesterer, Jessica L., Germain, Ronald N., Shi, Tujin, Chee, Mark S., Budnik, Bogdan A., Yates, John R., Chait, Brian T., Moffitt, Jeffery R., Smith, Richard D., and Srivastava, Sudhir. National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions. United States: N. p., 2020. Web. doi:10.1021/acs.jproteome.0c00021.
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Kagan, Jacob, Moritz, Robert L., Mazurchuk, Richard, Lee, Je Hyuk, Kharchenko, Peter Vasili, Rozenblatt-Rosen, Orit, Ruppin, Eytan, Edfors, Fredrik, Ginty, Fiona, Goltsev, Yury, Wells, James A., LaCava, John, Riesterer, Jessica L., Germain, Ronald N., Shi, Tujin, Chee, Mark S., Budnik, Bogdan A., Yates, John R., Chait, Brian T., Moffitt, Jeffery R., Smith, Richard D., & Srivastava, Sudhir. National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions. United States. https://doi.org/10.1021/acs.jproteome.0c00021
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Kagan, Jacob, Moritz, Robert L., Mazurchuk, Richard, Lee, Je Hyuk, Kharchenko, Peter Vasili, Rozenblatt-Rosen, Orit, Ruppin, Eytan, Edfors, Fredrik, Ginty, Fiona, Goltsev, Yury, Wells, James A., LaCava, John, Riesterer, Jessica L., Germain, Ronald N., Shi, Tujin, Chee, Mark S., Budnik, Bogdan A., Yates, John R., Chait, Brian T., Moffitt, Jeffery R., Smith, Richard D., and Srivastava, Sudhir. Thu . "National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions". United States. https://doi.org/10.1021/acs.jproteome.0c00021. https://www.osti.gov/servlets/purl/1639039.
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@article{osti_1639039,
title = {National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions},
author = {Kagan, Jacob and Moritz, Robert L. and Mazurchuk, Richard and Lee, Je Hyuk and Kharchenko, Peter Vasili and Rozenblatt-Rosen, Orit and Ruppin, Eytan and Edfors, Fredrik and Ginty, Fiona and Goltsev, Yury and Wells, James A. and LaCava, John and Riesterer, Jessica L. and Germain, Ronald N. and Shi, Tujin and Chee, Mark S. and Budnik, Bogdan A. and Yates, John R. and Chait, Brian T. and Moffitt, Jeffery R. and Smith, Richard D. and Srivastava, Sudhir},
abstractNote = {A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts’ opinion on the development and application of multi-omic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular and functional aberrations within the lesion and within individual cells. Additionally, single-cell proteomic data will be essential for the establishment of new tools that with searchable and scalable features that include spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included: • The best way/s to analyze single-cells from fresh and preserved tissue • Detection and analysis of secreted molecules and from single cells, especially from a tissue slice • Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment • Multi-omic integration of data to support and inform proteomic measurements • Subcellular organelles – identifying abnormal structure, function, distribution and location within individual premalignant and malignant cells • How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post translational modifications (PTM) • The depth of coverage measured concurrently using single-cell techniques • Quantitation - absolute or semiquantitative? • Single methodology or multiplexed combinations? • Application of analytical methods for identification of biologically significant subsets • Data visualization of N-dimensional datasets • How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME) • Associations between intrinsic cellular processes and extrinsic stimuli • How to predict cellular responses to stress inducing stimuli • Identification of new markers for prediction of progression from precursor, benign and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells • Identification of new targets for immunoprevention or immunotherapy – identification of neoantigens and surfactome of individual cells within a lesion},
doi = {10.1021/acs.jproteome.0c00021},
journal = {Journal of Proteome Research},
number = 5,
volume = 19,
place = {United States},
year = {Thu Mar 12 00:00:00 EDT 2020},
month = {Thu Mar 12 00:00:00 EDT 2020}
}
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https://doi.org/10.1021/acs.jproteome.0c00021
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Ion Mobility Separations of Isomers based upon Long Path Length Structures for Lossless Ion Manipulations Combined with Mass Spectrometry
journal, July 2016

  • Deng, Liulin; Ibrahim, Yehia M.; Baker, Erin S.
  • ChemistrySelect, Vol. 1, Issue 10
  • DOI: 10.1002/slct.201600460

Serpentine Ultralong Path with Extended Routing (SUPER) High Resolution Traveling Wave Ion Mobility-MS using Structures for Lossless Ion Manipulations
journal, April 2017

Characterization and Optimization of Multiplexed Quantitative Analyses Using High-Field Asymmetric-Waveform Ion Mobility Mass Spectrometry
journal, January 2019

Optimized Workflow for Multiplexed Phosphorylation Analysis of TMT-Labeled Peptides Using High-Field Asymmetric Waveform Ion Mobility Spectrometry
journal, November 2019

Highly parallel single-molecule identification of proteins in zeptomole-scale mixtures
journal, October 2018

  • Swaminathan, Jagannath; Boulgakov, Alexander A.; Hernandez, Erik T.
  • Nature Biotechnology, Vol. 36, Issue 11
  • DOI: 10.1038/nbt.4278
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