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

Cemal Erdem, Sean M. Gross, Laura M. Heiser () and Marc R. Birtwistle ()
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Cemal Erdem: Clemson University
Sean M. Gross: Oregon Health & Science University
Laura M. Heiser: Oregon Health & Science University
Marc R. Birtwistle: Clemson University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-39729-2

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