Please use this identifier to cite or link to this item:
Title: A densely interconnected genome-wide network of micrornas and oncogenic pathways revealed using gene expression signatures
Authors: Ooi, C.H. 
Oh, H.K.
Wang, H.Z.
Tan, A.L.K.
Wu, J.
Lee, M.
Rha, S.Y.
Chung, H.C.
Virshup, D.M.
Tan, P. 
Issue Date: Dec-2011
Citation: Ooi, C.H., Oh, H.K., Wang, H.Z., Tan, A.L.K., Wu, J., Lee, M., Rha, S.Y., Chung, H.C., Virshup, D.M., Tan, P. (2011-12). A densely interconnected genome-wide network of micrornas and oncogenic pathways revealed using gene expression signatures. PLoS Genetics 7 (12) : -. ScholarBank@NUS Repository.
Abstract: MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping &300 gene expression signatures to &700 primary tumor profiles, we constructed a genome-wide miRNA-pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA-pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA-pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes ("hubs"), most nodes in the miRNA-pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA-pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available. © 2011 Ooi et al.
Source Title: PLoS Genetics
ISSN: 15537390
DOI: 10.1371/journal.pgen.1002415
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2011-densely_interconnected_genome-wide_network_microRNAs-published.pdf2.02 MBAdobe PDF




checked on Sep 27, 2021


checked on Sep 27, 2021

Page view(s)

checked on Sep 23, 2021


checked on Sep 23, 2021

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.