A human functional protein interaction network and its application to cancer data analysis

Guanming Wu, Xin Feng, Lincoln Stein

Research output: Contribution to journalArticle

362 Citations (Scopus)

Abstract

Background: One challenge facing biologists is to tease out useful information from massive data sets for further analysis. A pathway-based analysis may shed light by projecting candidate genes onto protein functional relationship networks. We are building such a pathway-based analysis system.Results: We have constructed a protein functional interaction network by extending curated pathways with non-curated sources of information, including protein-protein interactions, gene coexpression, protein domain interaction, Gene Ontology (GO) annotations and text-mined protein interactions, which cover close to 50% of the human proteome. By applying this network to two glioblastoma multiforme (GBM) data sets and projecting cancer candidate genes onto the network, we found that the majority of GBM candidate genes form a cluster and are closer than expected by chance, and the majority of GBM samples have sequence-altered genes in two network modules, one mainly comprising genes whose products are localized in the cytoplasm and plasma membrane, and another comprising gene products in the nucleus. Both modules are highly enriched in known oncogenes, tumor suppressors and genes involved in signal transduction. Similar network patterns were also found in breast, colorectal and pancreatic cancers.Conclusions: We have built a highly reliable functional interaction network upon expert-curated pathways and applied this network to the analysis of two genome-wide GBM and several other cancer data sets. The network patterns revealed from our results suggest common mechanisms in the cancer biology. Our system should provide a foundation for a network or pathway-based analysis platform for cancer and other diseases.

Original languageEnglish (US)
Article numberR53
JournalGenome Biology
Volume11
Issue number5
DOIs
StatePublished - May 19 2010

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Protein Interaction Maps
cancer
Glioblastoma
data analysis
neoplasms
protein
gene
Neoplasms
Proteins
genes
proteins
Genes
Molecular Sequence Annotation
Gene Ontology
Gene Regulatory Networks
Neoplasm Genes
Proteome
Tumor Suppressor Genes
Pancreatic Neoplasms
Oncogenes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

A human functional protein interaction network and its application to cancer data analysis. / Wu, Guanming; Feng, Xin; Stein, Lincoln.

In: Genome Biology, Vol. 11, No. 5, R53, 19.05.2010.

Research output: Contribution to journalArticle

Wu, Guanming ; Feng, Xin ; Stein, Lincoln. / A human functional protein interaction network and its application to cancer data analysis. In: Genome Biology. 2010 ; Vol. 11, No. 5.
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