Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification

Cellular composition and structural organization of cells in the tissue determine effective antitumor response and can predict patient outcome and therapy response. Here we present Seg-SOM, a method for dimensionality reduction of cell morphology in H&E-stained tissue images. Seg-SOM resolve...

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Main Authors: Edwin Yuan, Magdalena Matusiak, Korsuk Sirinukunwattana, Sushama Varma, Łukasz Kidziński, Robert West
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.765923/full
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author Edwin Yuan
Magdalena Matusiak
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Sushama Varma
Łukasz Kidziński
Robert West
author_facet Edwin Yuan
Magdalena Matusiak
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Sushama Varma
Łukasz Kidziński
Robert West
author_sort Edwin Yuan
collection DOAJ
description Cellular composition and structural organization of cells in the tissue determine effective antitumor response and can predict patient outcome and therapy response. Here we present Seg-SOM, a method for dimensionality reduction of cell morphology in H&E-stained tissue images. Seg-SOM resolves cellular tissue heterogeneity and reveals complex tissue architecture. We leverage a self-organizing map (SOM) artificial neural network to group cells based on morphological features like shape and size. Seg-SOM allows for cell segmentation, systematic classification, and in silico cell labeling. We apply the Seg-SOM to a dataset of breast cancer progression images and find that clustering of SOM classes reveals groups of cells corresponding to fibroblasts, epithelial cells, and lymphocytes. We show that labeling the Lymphocyte SOM class on the breast tissue images accurately estimates lymphocytic infiltration. We further demonstrate how to use Seq-SOM in combination with non-negative matrix factorization to statistically describe the interaction of cell subtypes and use the interaction information as highly interpretable features for a histological classifier. Our work provides a framework for use of SOM in human pathology to resolve cellular composition of complex human tissues. We provide a python implementation and an easy-to-use docker deployment, enabling researchers to effortlessly featurize digitalized H&E-stained tissue.
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spelling doaj.art-c9c959eabd42499e9f1f8a569043f3da2022-12-21T20:38:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.765923765923Self-Organizing Maps for Cellular In Silico Staining and Cell Substate ClassificationEdwin Yuan0Magdalena Matusiak1Korsuk Sirinukunwattana2Korsuk Sirinukunwattana3Korsuk Sirinukunwattana4Korsuk Sirinukunwattana5Sushama Varma6Łukasz Kidziński7Robert West8Department of Applied Physics, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesInstitute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United KingdomGround Truth Labs, Oxford, United KingdomBig Data Institute/Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United KingdomNational Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford University National Health Service (NHS) Foundation Trust, Oxford, United KingdomDepartment of Pathology, Stanford University, Stanford, CA, United StatesDepartment of Bioengineering, Stanford University, Stanford, CA, United StatesDepartment of Pathology, Stanford University, Stanford, CA, United StatesCellular composition and structural organization of cells in the tissue determine effective antitumor response and can predict patient outcome and therapy response. Here we present Seg-SOM, a method for dimensionality reduction of cell morphology in H&E-stained tissue images. Seg-SOM resolves cellular tissue heterogeneity and reveals complex tissue architecture. We leverage a self-organizing map (SOM) artificial neural network to group cells based on morphological features like shape and size. Seg-SOM allows for cell segmentation, systematic classification, and in silico cell labeling. We apply the Seg-SOM to a dataset of breast cancer progression images and find that clustering of SOM classes reveals groups of cells corresponding to fibroblasts, epithelial cells, and lymphocytes. We show that labeling the Lymphocyte SOM class on the breast tissue images accurately estimates lymphocytic infiltration. We further demonstrate how to use Seq-SOM in combination with non-negative matrix factorization to statistically describe the interaction of cell subtypes and use the interaction information as highly interpretable features for a histological classifier. Our work provides a framework for use of SOM in human pathology to resolve cellular composition of complex human tissues. We provide a python implementation and an easy-to-use docker deployment, enabling researchers to effortlessly featurize digitalized H&E-stained tissue.https://www.frontiersin.org/articles/10.3389/fimmu.2021.765923/fullself-organizationin silico staininge-pathologycell subtype classificationsegmentation
spellingShingle Edwin Yuan
Magdalena Matusiak
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Korsuk Sirinukunwattana
Sushama Varma
Łukasz Kidziński
Robert West
Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
Frontiers in Immunology
self-organization
in silico staining
e-pathology
cell subtype classification
segmentation
title Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
title_full Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
title_fullStr Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
title_full_unstemmed Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
title_short Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
title_sort self organizing maps for cellular in silico staining and cell substate classification
topic self-organization
in silico staining
e-pathology
cell subtype classification
segmentation
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.765923/full
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