Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/41477
Title: | Measures of spatial heterogeneity in the liver tissue micro-environment as predictive factors for fibrosis score | Authors: | AGTEN, Annelies Blazquez-Moreno, Alfonso Crabbe, Marjolein Tuefferd, Marianne Goehlmann, Hinrich GEYS, Helena Peng, Cheng-Yuan CLAES, Jari NEYENS, Thomas FAES, Christel |
Issue Date: | 2023 | Publisher: | PERGAMON-ELSEVIER SCIENCE LTD | Source: | COMPUTERS IN BIOLOGY AND MEDICINE, 165 (Art N° 107382) | Abstract: | The organization and interaction between hepatocytes and other hepatic non-parenchymal cells plays a pivotal role in maintaining normal liver function and structure. Although spatial heterogeneity within the tumor micro environment has been proven to be a fundamental feature in cancer progression, the role of liver tissue topology and micro-environmental factors in the context of liver damage in chronic infection has not been widely studied yet. We obtained images from 110 core needle biopsies from a cohort of chronic hepatitis B patients with different fibrosis stages according to METAVIR score. The tissue sections were immunofluorescently stained and imaged to determine the locations of CD45 positive immune cells and HBsAg-negative and HBsAg-positive hepatocytes within the tissue. We applied several descriptive techniques adopted from ecology, including Getis- Ord, the Shannon Index and the Morisita-Horn Index, to quantify the extent to which immune cells and different types of liver cells co-localize in the tissue biopsies. Additionally, we modeled the spatial distribution of the different cell types using a joint log-Gaussian Cox process and proposed several features to quantify spatial heterogeneity. We then related these measures to the patient fibrosis stage by using a linear discriminant analysis approach. Our analysis revealed that the co-localization of HBsAg-negative hepatocytes with immune cells and the co-localization of HBsAg-positive hepatocytes with immune cells are equally important factors for explaining the METAVIR score in chronic hepatitis B patients. Moreover, we found that if we allow for an error of 1 on the METAVIR score, we are able to reach an accuracy of around 80%. With this study we demonstrate how methods adopted from ecology and applied to the liver tissue micro-environment can be used to quantify heterogeneity and how these approaches can be valuable in biomarker analyses for liver topology. | Notes: | Agten, A (corresponding author), UHasselt Hasselt Univ, Data Sci Inst, Agoralaan 1, BE-3590 Diepenbeek, Belgium. annelies.agten@uhasselt.be |
Keywords: | Liver fibrosis;Tissue micro-environment;Spatial heterogeneity;Immunofluorescence;Classification;Biomarker analysis;Getis-ord;Log-Gaussian cox;Point process;Morisita-Horn;Shannon diversity index;Single cell data;Chronic hepatitis B;Cell type co-localization;Immunology;Hepatocyte immune cell interaction;Immune hotspot | Document URI: | http://hdl.handle.net/1942/41477 | ISSN: | 0010-4825 | e-ISSN: | 1879-0534 | DOI: | 10.1016/j.compbiomed.2023.107382 | ISI #: | 001072010900001 | Rights: | 2023 Elsevier Ltd. All rights reserved | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Measures of spatial heterogeneity in the liver tissue micro-environment as predictive factors for fibrosis score.pdf Restricted Access | Published version | 3.19 MB | Adobe PDF | View/Open Request a copy |
Liver Topology manuscript REVISION.pdf Until 2024-10-31 | Peer-reviewed author version | 2.65 MB | Adobe PDF | View/Open Request a copy |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.