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MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms

Robust identification of context-specific network features that control cellular phenotypes remains a challenge. We here introduce MOBILE (Multi-Omics Binary Integration via Lasso Ensembles) to nominate molecular features associated with cellular phenotypes and pathways. First, we use MOBILE to nomi...

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Autores principales: Erdem, Cemal, Gross, Sean M., Heiser, Laura M., Birtwistle, Marc R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326020/
https://www.ncbi.nlm.nih.gov/pubmed/37414767
http://dx.doi.org/10.1038/s41467-023-39729-2
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author Erdem, Cemal
Gross, Sean M.
Heiser, Laura M.
Birtwistle, Marc R.
author_facet Erdem, Cemal
Gross, Sean M.
Heiser, Laura M.
Birtwistle, Marc R.
author_sort Erdem, Cemal
collection PubMed
description Robust identification of context-specific network features that control cellular phenotypes remains a challenge. We here introduce MOBILE (Multi-Omics Binary Integration via Lasso Ensembles) to nominate molecular features associated with cellular phenotypes and pathways. First, we use MOBILE to nominate mechanisms of interferon-γ (IFNγ) regulated PD-L1 expression. Our analyses suggest that IFNγ-controlled PD-L1 expression involves BST2, CLIC2, FAM83D, ACSL5, and HIST2H2AA3 genes, which were supported by prior literature. We also compare networks activated by related family members transforming growth factor-beta 1 (TGFβ1) and bone morphogenetic protein 2 (BMP2) and find that differences in ligand-induced changes in cell size and clustering properties are related to differences in laminin/collagen pathway activity. Finally, we demonstrate the broad applicability and adaptability of MOBILE by analyzing publicly available molecular datasets to investigate breast cancer subtype specific networks. Given the ever-growing availability of multi-omics datasets, we envision that MOBILE will be broadly useful for identification of context-specific molecular features and pathways.
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spelling pubmed-103260202023-07-08 MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms Erdem, Cemal Gross, Sean M. Heiser, Laura M. Birtwistle, Marc R. Nat Commun Article Robust identification of context-specific network features that control cellular phenotypes remains a challenge. We here introduce MOBILE (Multi-Omics Binary Integration via Lasso Ensembles) to nominate molecular features associated with cellular phenotypes and pathways. First, we use MOBILE to nominate mechanisms of interferon-γ (IFNγ) regulated PD-L1 expression. Our analyses suggest that IFNγ-controlled PD-L1 expression involves BST2, CLIC2, FAM83D, ACSL5, and HIST2H2AA3 genes, which were supported by prior literature. We also compare networks activated by related family members transforming growth factor-beta 1 (TGFβ1) and bone morphogenetic protein 2 (BMP2) and find that differences in ligand-induced changes in cell size and clustering properties are related to differences in laminin/collagen pathway activity. Finally, we demonstrate the broad applicability and adaptability of MOBILE by analyzing publicly available molecular datasets to investigate breast cancer subtype specific networks. Given the ever-growing availability of multi-omics datasets, we envision that MOBILE will be broadly useful for identification of context-specific molecular features and pathways. Nature Publishing Group UK 2023-07-06 /pmc/articles/PMC10326020/ /pubmed/37414767 http://dx.doi.org/10.1038/s41467-023-39729-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Erdem, Cemal
Gross, Sean M.
Heiser, Laura M.
Birtwistle, Marc R.
MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
title MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
title_full MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
title_fullStr MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
title_full_unstemmed MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
title_short MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
title_sort mobile pipeline enables identification of context-specific networks and regulatory mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326020/
https://www.ncbi.nlm.nih.gov/pubmed/37414767
http://dx.doi.org/10.1038/s41467-023-39729-2
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