A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis

Abstract Over the past decade, automation of digital image analysis has become commonplace in both research and clinical settings. Spurred by recent advances in artificial intelligence and machine learning (AI/ML), tissue sub-compartments and cellular phenotypes within those compartments can be iden...

Full description

Bibliographic Details
Main Authors: Edward D. Bonnevie, Eric Dobrzynski, Dylan Steiner, Deon Hildebrand, James Monslow, Mohan Singh, Vilma Decman, David L. Krull
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-49163-5
_version_ 1797398046307254272
author Edward D. Bonnevie
Eric Dobrzynski
Dylan Steiner
Deon Hildebrand
James Monslow
Mohan Singh
Vilma Decman
David L. Krull
author_facet Edward D. Bonnevie
Eric Dobrzynski
Dylan Steiner
Deon Hildebrand
James Monslow
Mohan Singh
Vilma Decman
David L. Krull
author_sort Edward D. Bonnevie
collection DOAJ
description Abstract Over the past decade, automation of digital image analysis has become commonplace in both research and clinical settings. Spurred by recent advances in artificial intelligence and machine learning (AI/ML), tissue sub-compartments and cellular phenotypes within those compartments can be identified with higher throughput and accuracy than ever before. Recently, immune checkpoints have emerged as potential targets for auto-immune diseases. As such, spatial identification of these proteins along with immune cell markers (e.g., CD3+/LAG3+ T-cells) is a crucial step in understanding the potential and/or efficacy of such treatments. Here, we describe a semi-automated imaging and analysis pipeline that identifies CD3+/LAG3+ cells in colorectal tissue sub-compartments. While chromogenic staining has been a clinical mainstay and the resulting brightfield images have been utilized in AI/ML approaches in the past, there are associated drawbacks in phenotyping algorithms that can be overcome by fluorescence imaging. To address these tradeoffs, we developed an analysis pipeline combining the strengths of brightfield and fluorescence images. In this assay, immunofluorescence imaging was conducted to identify phenotypes followed by coverslip removal and hematoxylin and eosin staining of the same section to inform an AI/ML tissue segmentation algorithm. This assay proved to be robust in both tissue segmentation and phenotyping, was compatible with automated workflows, and revealed presence of LAG3+ T-cells in ulcerative colitis biopsies with spatial context preserved.
first_indexed 2024-03-09T01:20:00Z
format Article
id doaj.art-e4d5d37e8b8a44a48b999a78c3bb3162
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-09T01:20:00Z
publishDate 2023-12-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-e4d5d37e8b8a44a48b999a78c3bb31622023-12-10T12:16:12ZengNature PortfolioScientific Reports2045-23222023-12-0113111210.1038/s41598-023-49163-5A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitisEdward D. Bonnevie0Eric Dobrzynski1Dylan Steiner2Deon Hildebrand3James Monslow4Mohan Singh5Vilma Decman6David L. Krull7Cellular Biomarkers, GSKCellular Biomarkers, GSKCellular Biomarkers, GSKNCS-Pathology, GSKCellular Biomarkers, GSKCellular Biomarkers, GSKCellular Biomarkers, GSKCellular Biomarkers, GSKAbstract Over the past decade, automation of digital image analysis has become commonplace in both research and clinical settings. Spurred by recent advances in artificial intelligence and machine learning (AI/ML), tissue sub-compartments and cellular phenotypes within those compartments can be identified with higher throughput and accuracy than ever before. Recently, immune checkpoints have emerged as potential targets for auto-immune diseases. As such, spatial identification of these proteins along with immune cell markers (e.g., CD3+/LAG3+ T-cells) is a crucial step in understanding the potential and/or efficacy of such treatments. Here, we describe a semi-automated imaging and analysis pipeline that identifies CD3+/LAG3+ cells in colorectal tissue sub-compartments. While chromogenic staining has been a clinical mainstay and the resulting brightfield images have been utilized in AI/ML approaches in the past, there are associated drawbacks in phenotyping algorithms that can be overcome by fluorescence imaging. To address these tradeoffs, we developed an analysis pipeline combining the strengths of brightfield and fluorescence images. In this assay, immunofluorescence imaging was conducted to identify phenotypes followed by coverslip removal and hematoxylin and eosin staining of the same section to inform an AI/ML tissue segmentation algorithm. This assay proved to be robust in both tissue segmentation and phenotyping, was compatible with automated workflows, and revealed presence of LAG3+ T-cells in ulcerative colitis biopsies with spatial context preserved.https://doi.org/10.1038/s41598-023-49163-5
spellingShingle Edward D. Bonnevie
Eric Dobrzynski
Dylan Steiner
Deon Hildebrand
James Monslow
Mohan Singh
Vilma Decman
David L. Krull
A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis
Scientific Reports
title A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis
title_full A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis
title_fullStr A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis
title_full_unstemmed A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis
title_short A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis
title_sort machine learning approach toward automating spatial identification of lag3 cd3 cells in ulcerative colitis
url https://doi.org/10.1038/s41598-023-49163-5
work_keys_str_mv AT edwarddbonnevie amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT ericdobrzynski amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT dylansteiner amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT deonhildebrand amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT jamesmonslow amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT mohansingh amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT vilmadecman amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT davidlkrull amachinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT edwarddbonnevie machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT ericdobrzynski machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT dylansteiner machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT deonhildebrand machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT jamesmonslow machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT mohansingh machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT vilmadecman machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis
AT davidlkrull machinelearningapproachtowardautomatingspatialidentificationoflag3cd3cellsinulcerativecolitis