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MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA.ORCID iD: 0000-0003-3663-3646
2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 3991Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 14, no 1, article id 3991
National Category
Bioinformatics and Systems Biology
Identifiers
URN: urn:nbn:se:umu:diva-218251DOI: 10.1038/s41467-023-39729-2OAI: oai:DiVA.org:umu-218251DiVA, id: diva2:1820882
Available from: 2023-12-19 Created: 2023-12-19 Last updated: 2024-04-16Bibliographically approved

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Erdem, Cemal

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CiteExportLink to record
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