Extended correlation functions for spatial analysis of multiplex imaging data

Imaging platforms for generating highly multiplexed histological images are being continually developed and improved. Significant improvements have also been made in the accuracy of methods for automated cell segmentation and classification. However, less attention has focused on the quantification...

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Main Authors: Bull, J, Mulholland, E, Leedham, S, Byrne, H
Format: Journal article
Language:English
Published: Cambridge University Press 2024
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author Bull, J
Mulholland, E
Leedham, S
Byrne, H
author_facet Bull, J
Mulholland, E
Leedham, S
Byrne, H
author_sort Bull, J
collection OXFORD
description Imaging platforms for generating highly multiplexed histological images are being continually developed and improved. Significant improvements have also been made in the accuracy of methods for automated cell segmentation and classification. However, less attention has focused on the quantification and analysis of the resulting point clouds, which describe the spatial coordinates of individual cells. We focus here on a particular spatial statistical method, the cross-pair correlation function (cross-PCF), which can identify positive and negative spatial correlation between cells across a range of length scales. However, limitations of the cross-PCF hinder its widespread application to multiplexed histology. For example, it can only consider relations between pairs of cells, and cells must be classified using discrete categorical labels (rather than labeling continuous labels such as stain intensity). In this paper, we present three extensions to the cross-PCF which address these limitations and permit more detailed analysis of multiplex images: topographical correlation maps can visualize local clustering and exclusion between cells; neighbourhood correlation functions can identify colocalization of two or more cell types; and weighted-PCFs describe spatial correlation between points with continuous (rather than discrete) labels. We apply the extended PCFs to synthetic and biological datasets in order to demonstrate the insight that they can generate.
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spelling oxford-uuid:f3ac7b7e-b315-431f-8e72-291cf0620eef2024-11-29T11:49:30ZExtended correlation functions for spatial analysis of multiplex imaging dataJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f3ac7b7e-b315-431f-8e72-291cf0620eefEnglishSymplectic ElementsCambridge University Press2024Bull, JMulholland, ELeedham, SByrne, HImaging platforms for generating highly multiplexed histological images are being continually developed and improved. Significant improvements have also been made in the accuracy of methods for automated cell segmentation and classification. However, less attention has focused on the quantification and analysis of the resulting point clouds, which describe the spatial coordinates of individual cells. We focus here on a particular spatial statistical method, the cross-pair correlation function (cross-PCF), which can identify positive and negative spatial correlation between cells across a range of length scales. However, limitations of the cross-PCF hinder its widespread application to multiplexed histology. For example, it can only consider relations between pairs of cells, and cells must be classified using discrete categorical labels (rather than labeling continuous labels such as stain intensity). In this paper, we present three extensions to the cross-PCF which address these limitations and permit more detailed analysis of multiplex images: topographical correlation maps can visualize local clustering and exclusion between cells; neighbourhood correlation functions can identify colocalization of two or more cell types; and weighted-PCFs describe spatial correlation between points with continuous (rather than discrete) labels. We apply the extended PCFs to synthetic and biological datasets in order to demonstrate the insight that they can generate.
spellingShingle Bull, J
Mulholland, E
Leedham, S
Byrne, H
Extended correlation functions for spatial analysis of multiplex imaging data
title Extended correlation functions for spatial analysis of multiplex imaging data
title_full Extended correlation functions for spatial analysis of multiplex imaging data
title_fullStr Extended correlation functions for spatial analysis of multiplex imaging data
title_full_unstemmed Extended correlation functions for spatial analysis of multiplex imaging data
title_short Extended correlation functions for spatial analysis of multiplex imaging data
title_sort extended correlation functions for spatial analysis of multiplex imaging data
work_keys_str_mv AT bullj extendedcorrelationfunctionsforspatialanalysisofmultipleximagingdata
AT mulhollande extendedcorrelationfunctionsforspatialanalysisofmultipleximagingdata
AT leedhams extendedcorrelationfunctionsforspatialanalysisofmultipleximagingdata
AT byrneh extendedcorrelationfunctionsforspatialanalysisofmultipleximagingdata