SAMNet: a network-based approach to integrate multi-dimensional high throughput datasets.

TitleSAMNet: a network-based approach to integrate multi-dimensional high throughput datasets.
Publication TypeJournal Article
Year of Publication2012
AuthorsGosline, SJC, Spencer, SJ, Ursu, O, Fraenkel, E
JournalIntegr Biol (Camb)
Date Published2012 Nov
KeywordsAlgorithms, Carcinoma, Non-Small-Cell Lung, Data Interpretation, Statistical, Databases, Genetic, Epithelial-Mesenchymal Transition, Gene Expression, Gene Regulatory Networks, High-Throughput Screening Assays, Humans, Lung Neoplasms, Piperazines, Protein Kinase Inhibitors, Pyrimidines, RNA, Fungal, RNA, Messenger, RNA, Neoplasm, Saccharomyces cerevisiae, Signal Transduction, Systems Biology, Transition Elements

The rapid development of high throughput biotechnologies has led to an onslaught of data describing genetic perturbations and changes in mRNA and protein levels in the cell. Because each assay provides a one-dimensional snapshot of active signaling pathways, it has become desirable to perform multiple assays (e.g. mRNA expression and phospho-proteomics) to measure a single condition. However, as experiments expand to accommodate various cellular conditions, proper analysis and interpretation of these data have become more challenging. Here we introduce a novel approach called SAMNet, for Simultaneous Analysis of Multiple Networks, that is able to interpret diverse assays over multiple perturbations. The algorithm uses a constrained optimization approach to integrate mRNA expression data with upstream genes, selecting edges in the protein-protein interaction network that best explain the changes across all perturbations. The result is a putative set of protein interactions that succinctly summarizes the results from all experiments, highlighting the network elements unique to each perturbation. We evaluated SAMNet in both yeast and human datasets. The yeast dataset measured the cellular response to seven different transition metals, and the human dataset measured cellular changes in four different lung cancer models of Epithelial-Mesenchymal Transition (EMT), a crucial process in tumor metastasis. SAMNet was able to identify canonical yeast metal-processing genes unique to each commodity in the yeast dataset, as well as human genes such as β-catenin and TCF7L2/TCF4 that are required for EMT signaling but escaped detection in the mRNA and phospho-proteomic data. Moreover, SAMNet also highlighted drugs likely to modulate EMT, identifying a series of less canonical genes known to be affected by the BCR-ABL inhibitor imatinib (Gleevec), suggesting a possible influence of this drug on EMT.

Alternate JournalIntegr Biol (Camb)
PubMed ID23060147
PubMed Central IDPMC3501250
Grant ListR01 GM089903 / GM / NIGMS NIH HHS / United States
R01GM089903 / GM / NIGMS NIH HHS / United States
U54 CA112967 / CA / NCI NIH HHS / United States
U54CA112967 / CA / NCI NIH HHS / United States