Systems approach for congruence and selection of cancer models towards precision medicine.

Cancer models are instrumental as a substitute for human studies and to expedite basic, translational, and clinical cancer research. For a given cancer type, a wide selection of models, such as cell lines, patient-derived xenografts, organoids and genetically modified murine models, are often availa...

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Main Authors: Jian Zou, Osama Shah, Yu-Chiao Chiu, Tianzhou Ma, Jennifer M Atkinson, Steffi Oesterreich, Adrian V Lee, George C Tseng
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011754&type=printable
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author Jian Zou
Osama Shah
Yu-Chiao Chiu
Tianzhou Ma
Jennifer M Atkinson
Steffi Oesterreich
Adrian V Lee
George C Tseng
author_facet Jian Zou
Osama Shah
Yu-Chiao Chiu
Tianzhou Ma
Jennifer M Atkinson
Steffi Oesterreich
Adrian V Lee
George C Tseng
author_sort Jian Zou
collection DOAJ
description Cancer models are instrumental as a substitute for human studies and to expedite basic, translational, and clinical cancer research. For a given cancer type, a wide selection of models, such as cell lines, patient-derived xenografts, organoids and genetically modified murine models, are often available to researchers. However, how to quantify their congruence to human tumors and to select the most appropriate cancer model is a largely unsolved issue. Here, we present Congruence Analysis and Selection of CAncer Models (CASCAM), a statistical and machine learning framework for authenticating and selecting the most representative cancer models in a pathway-specific manner using transcriptomic data. CASCAM provides harmonization between human tumor and cancer model omics data, systematic congruence quantification, and pathway-based topological visualization to determine the most appropriate cancer model selection. The systems approach is presented using invasive lobular breast carcinoma (ILC) subtype and suggesting CAMA1 followed by UACC3133 as the most representative cell lines for ILC research. Two additional case studies for triple negative breast cancer (TNBC) and patient-derived xenograft/organoid (PDX/PDO) are further investigated. CASCAM is generalizable to any cancer subtype and will authenticate cancer models for faithful non-human preclinical research towards precision medicine.
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spelling doaj.art-d6056c710d1441368e8499b836e820b42024-02-14T05:31:21ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582024-01-01201e101175410.1371/journal.pcbi.1011754Systems approach for congruence and selection of cancer models towards precision medicine.Jian ZouOsama ShahYu-Chiao ChiuTianzhou MaJennifer M AtkinsonSteffi OesterreichAdrian V LeeGeorge C TsengCancer models are instrumental as a substitute for human studies and to expedite basic, translational, and clinical cancer research. For a given cancer type, a wide selection of models, such as cell lines, patient-derived xenografts, organoids and genetically modified murine models, are often available to researchers. However, how to quantify their congruence to human tumors and to select the most appropriate cancer model is a largely unsolved issue. Here, we present Congruence Analysis and Selection of CAncer Models (CASCAM), a statistical and machine learning framework for authenticating and selecting the most representative cancer models in a pathway-specific manner using transcriptomic data. CASCAM provides harmonization between human tumor and cancer model omics data, systematic congruence quantification, and pathway-based topological visualization to determine the most appropriate cancer model selection. The systems approach is presented using invasive lobular breast carcinoma (ILC) subtype and suggesting CAMA1 followed by UACC3133 as the most representative cell lines for ILC research. Two additional case studies for triple negative breast cancer (TNBC) and patient-derived xenograft/organoid (PDX/PDO) are further investigated. CASCAM is generalizable to any cancer subtype and will authenticate cancer models for faithful non-human preclinical research towards precision medicine.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011754&type=printable
spellingShingle Jian Zou
Osama Shah
Yu-Chiao Chiu
Tianzhou Ma
Jennifer M Atkinson
Steffi Oesterreich
Adrian V Lee
George C Tseng
Systems approach for congruence and selection of cancer models towards precision medicine.
PLoS Computational Biology
title Systems approach for congruence and selection of cancer models towards precision medicine.
title_full Systems approach for congruence and selection of cancer models towards precision medicine.
title_fullStr Systems approach for congruence and selection of cancer models towards precision medicine.
title_full_unstemmed Systems approach for congruence and selection of cancer models towards precision medicine.
title_short Systems approach for congruence and selection of cancer models towards precision medicine.
title_sort systems approach for congruence and selection of cancer models towards precision medicine
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011754&type=printable
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