Abstract
AbstractRobust 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.
Funder
U.S. Department of Health & Human Services | National Institutes of Health
C.E. was an NIH-LINCS Postdoctoral Fellow.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
1 articles.
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