Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images

Multiplex imaging technologies are now routinely capable of measuring more than 40 antibody-labeled parameters in single cells. However, lateral spillage of signals in densely packed tissues presents an obstacle to the assignment of high-dimensional spatial features to individual cells for accurate...

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Main Authors: Yunhao Bai, Bokai Zhu, Xavier Rovira-Clave, Han Chen, Maxim Markovic, Chi Ngai Chan, Tung-Hung Su, David R. McIlwain, Jacob D. Estes, Leeat Keren, Garry P. Nolan, Sizun Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.652631/full
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author Yunhao Bai
Yunhao Bai
Bokai Zhu
Bokai Zhu
Xavier Rovira-Clave
Han Chen
Maxim Markovic
Chi Ngai Chan
Tung-Hung Su
Tung-Hung Su
David R. McIlwain
Jacob D. Estes
Leeat Keren
Leeat Keren
Garry P. Nolan
Sizun Jiang
Sizun Jiang
author_facet Yunhao Bai
Yunhao Bai
Bokai Zhu
Bokai Zhu
Xavier Rovira-Clave
Han Chen
Maxim Markovic
Chi Ngai Chan
Tung-Hung Su
Tung-Hung Su
David R. McIlwain
Jacob D. Estes
Leeat Keren
Leeat Keren
Garry P. Nolan
Sizun Jiang
Sizun Jiang
author_sort Yunhao Bai
collection DOAJ
description Multiplex imaging technologies are now routinely capable of measuring more than 40 antibody-labeled parameters in single cells. However, lateral spillage of signals in densely packed tissues presents an obstacle to the assignment of high-dimensional spatial features to individual cells for accurate cell-type annotation. We devised a method to correct for lateral spillage of cell surface markers between adjacent cells termed REinforcement Dynamic Spillover EliminAtion (REDSEA). The use of REDSEA decreased contaminating signals from neighboring cells. It improved the recovery of marker signals across both isotopic (i.e., Multiplexed Ion Beam Imaging) and immunofluorescent (i.e., Cyclic Immunofluorescence) multiplexed images resulting in a marked improvement in cell-type classification.
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spelling doaj.art-a231bbf0fefd4cca83ac3f75a764e8ae2022-12-21T21:25:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.652631652631Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed ImagesYunhao Bai0Yunhao Bai1Bokai Zhu2Bokai Zhu3Xavier Rovira-Clave4Han Chen5Maxim Markovic6Chi Ngai Chan7Tung-Hung Su8Tung-Hung Su9David R. McIlwain10Jacob D. Estes11Leeat Keren12Leeat Keren13Garry P. Nolan14Sizun Jiang15Sizun Jiang16Department of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Chemistry, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesVaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanDepartment of Pathology, Stanford University, Stanford, CA, United StatesVaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, IsraelDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesMultiplex imaging technologies are now routinely capable of measuring more than 40 antibody-labeled parameters in single cells. However, lateral spillage of signals in densely packed tissues presents an obstacle to the assignment of high-dimensional spatial features to individual cells for accurate cell-type annotation. We devised a method to correct for lateral spillage of cell surface markers between adjacent cells termed REinforcement Dynamic Spillover EliminAtion (REDSEA). The use of REDSEA decreased contaminating signals from neighboring cells. It improved the recovery of marker signals across both isotopic (i.e., Multiplexed Ion Beam Imaging) and immunofluorescent (i.e., Cyclic Immunofluorescence) multiplexed images resulting in a marked improvement in cell-type classification.https://www.frontiersin.org/articles/10.3389/fimmu.2021.652631/fullmultiplexed tissue imagingspatial proteomicssignal spilloverimage correctionsingle-cell biologycell annotation
spellingShingle Yunhao Bai
Yunhao Bai
Bokai Zhu
Bokai Zhu
Xavier Rovira-Clave
Han Chen
Maxim Markovic
Chi Ngai Chan
Tung-Hung Su
Tung-Hung Su
David R. McIlwain
Jacob D. Estes
Leeat Keren
Leeat Keren
Garry P. Nolan
Sizun Jiang
Sizun Jiang
Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images
Frontiers in Immunology
multiplexed tissue imaging
spatial proteomics
signal spillover
image correction
single-cell biology
cell annotation
title Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images
title_full Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images
title_fullStr Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images
title_full_unstemmed Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images
title_short Adjacent Cell Marker Lateral Spillover Compensation and Reinforcement for Multiplexed Images
title_sort adjacent cell marker lateral spillover compensation and reinforcement for multiplexed images
topic multiplexed tissue imaging
spatial proteomics
signal spillover
image correction
single-cell biology
cell annotation
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.652631/full
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