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A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures.

Publication ,  Journal Article
Ooi, CH; Oh, HK; Wang, HZ; Tan, ALK; Wu, J; Lee, M; Rha, SY; Chung, HC; Virshup, DM; Tan, P
Published in: PLoS Genet
December 2011

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.

Duke Scholars

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

December 2011

Volume

7

Issue

12

Start / End Page

e1002415

Location

United States

Related Subject Headings

  • Signal Transduction
  • RNA, Messenger
  • MicroRNAs
  • Humans
  • High-Throughput Screening Assays
  • Genome, Human
  • Gene Regulatory Networks
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ooi, C. H., Oh, H. K., Wang, H. Z., Tan, A. L. K., Wu, J., Lee, M., … Tan, P. (2011). A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures. PLoS Genet, 7(12), e1002415. https://doi.org/10.1371/journal.pgen.1002415
Ooi, Chia Huey, Hue Kian Oh, Hannah Zhu’ai Wang, Angie Lay Keng Tan, Jeanie Wu, Minghui Lee, Sun Young Rha, Hyun Cheol Chung, David Marc Virshup, and Patrick Tan. “A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures.PLoS Genet 7, no. 12 (December 2011): e1002415. https://doi.org/10.1371/journal.pgen.1002415.
Ooi CH, Oh HK, Wang HZ, Tan ALK, Wu J, Lee M, et al. A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures. PLoS Genet. 2011 Dec;7(12):e1002415.
Ooi, Chia Huey, et al. “A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures.PLoS Genet, vol. 7, no. 12, Dec. 2011, p. e1002415. Pubmed, doi:10.1371/journal.pgen.1002415.
Ooi CH, Oh HK, Wang HZ, Tan ALK, Wu J, Lee M, Rha SY, Chung HC, Virshup DM, Tan P. A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures. PLoS Genet. 2011 Dec;7(12):e1002415.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

December 2011

Volume

7

Issue

12

Start / End Page

e1002415

Location

United States

Related Subject Headings

  • Signal Transduction
  • RNA, Messenger
  • MicroRNAs
  • Humans
  • High-Throughput Screening Assays
  • Genome, Human
  • Gene Regulatory Networks
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
  • Developmental Biology